101

PosterSession

Poster Session 1Adult airway diseases

PE1-2 Clinical usefulness of serum and sputum YKL-40 in the management of asthma, ACO and COPD

Yasuhito Suzuki, Junpei Saito, Mami Rikimaru, Manabu Uematsu, Atsuro Fukuhara, Takefumi Nikaido, Naoko Fukuhara, Yoshinori Tanino,Yoko Shibata (Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Japan)

Background: We have previously reported sputum YKL-40 could be a biomarker for predicting neutrophilic airway inflammation in asthma,asthma-COPD overlap (ACO) and COPD. (Suzuki Y. JSA Congress 2019). However, little is known about relationship between sputum and serumYKL-40, and whether these biomarkers are associated with clinical features of asthma, ACO and COPD. Objectives: Firstly, to compare serum andsputum YKL-40 levels, and secondly, to evaluate associations between these biomarkers and parameters related to disease activity in asthma, ACOand COPD. Methods: Thirty nine asthmatics, 15 ACO patients and 19 COPD patients were recruited. Blood samplings, induced sputum tests, spi-rometry, FeNO measurements, and questionnaires (ACT, CAT, and mMRC dyspnea scale) were performed. Serum and sputum YKL-40 levels wereconcurrently measured by ELISA. With regard to sputum, sputum cell differentiations were also calculated. Results: There was a trend correlationbetween serum and sputum YKL-40. Serum as well as sputum YKL-40 levels in the COPD group were significantly higher than those in the asth-matic group (p<0.01). Additionally, serum YKL-40 levels in the ACO group were significantly higher than those in the asthmatic group (p<0.01), butsputum YKL-40 levels were not. There was no significant difference in serum and sputum YKL-40 levels between asthma, ACO, COPD severity.YKL-40 in both sputum and serum showed positive correlations with sputum neutrophils (p<0.05). Serum YKL-40, but not sputum YKL-40, werenegatively correlated with FEV1/FVC. In terms of relationships between YKL-40 and symptom questionnaires, serum YKL-40 had no associationswith symptom questionnaires in all three groups. However, sputum YKL-40 levels in the ACO and COPD groups with CAT score10 or mMRC score2 were higher than those with CAT score <10 or mMRC<2 (p<0.05). Conclusions: YKL-40 can be a marker of neutrophilic airway inflammation. Ad-ditionally, YKL-40 in sputum and serum may reflect distinct clinical features in asthma, ACO and COPD. Therefore, concomitant use of thesebiomarkers in addition to conventional tests may provide more useful information on evaluating disease activity. Further studies will be needed.

PE1-3 Exacerbation clusters demonstrate asthma and Chronic Obstructive Pulmonary Disease (COPD) overlap with distinct pheno-types

Kentaro Hyodo1,3), Hironori Masuko1), Hisayuki Oshima1), Rie Shigemasa1), Haruna Kitazawa1), Jun Kanazawa3), Hiroaki Iijima2), Takahide Kodama4),Akihiro Nomura5), Katsunori Kagohashi1), Hiroaki Sato1), Takefumi Saito3), Tohru Sakamoto1), Nobuyuki Hizawa1) (Department of Pulmonary Medi-cine (Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences), University of Tsukuba, Japan1); Tsukuba Medical Center,Japan2); National Hospital Organization Ibarakihigashi National Hospital, Japan3); Ryugasaki Saiseikai Hospital, Japan4); Ibaraki Seinan MedicalCenter Hospital, Japan5))

Rationale: Asthma and COPD are both characterized by an underlying chronic airway inflammation. Although exacerbations of asthma and COPDare complex and heterogeneous, they share similar risk factors. Whether the heterogeneity is similar between asthma and COPD exacerbations isunknown. In this study, we aimed to identify the phenotypes of chronic airway disease patients who have a history of exacerbations. Methods: Pa-tients with asthma (n=117), COPD (n=48) and Asthma-COPD overlap (ACO) (n=37) were recruited from University of Tsukuba hospitals, Japan.Asthma, COPD and ACO were diagnosed according to physician assessment consistent with definitions based on GINA, GOLD or the JRS guidelinesfor the management of ACO. Exacerbation was defined as an increase in symptoms necessitating a course of oral corticosteroids, antibiotic therapy,or both. For cluster analysis, we considered traits previously associated with acute exacerbation of chronic airway diseases, including COPD assess-ment test (CAT), frequency scale for the symptoms of GERD (FSSG), lung functions, smoking habits, blood eosinophil counts, and allergic rhinitis. Weperformed two-step cluster approach, which identifies groupings by running pre-clustering first and then by running hierarchical methods usingSPSS (Version 25.0). Results: Clustering approach revealed 5 subgroups of chronic airway diseases with a history of exacerbations, each with differ-ent percentages of patients with overlapping asthma and COPD. Cluster 1: n=56 (BA/COPD/ACO, 28/12/16), predominantly patients with high pe-ripheral blood eosinophils and mild lung function. Cluster 2: n=36 (4/27/5), patients with an impaired lung function and smoking history. Cluster 3: n=29 (10/8/11), patients with gastroesophageal reflux symptoms. Cluster 4: n=47 (42/2/3), predominantly non-atopic female. Cluster 5: n=34 (33/0/1), pa-tients with allergic rhinitis and high IgE levels. The average number of annual exacerbations for each cluster were 1.95, 1.86, 2.31, 1.89 and 3.68, re-spectively. Conclusion:We identified five clusters in chronic airway diseases with exacerbations. These phenotypes existed across conventional defi-nition of diseases, suggesting the importance of a personalized approach to acute exacerbation using phenotypes or traits rather than disease labels.

PE1-4 Anti-allergy medication utilization in patients with chronic cough

Xiao Luo1), Wei Shao5), Zuoyi Zhang5), Zhi Han2,5), Vasu Chandrasekaran3), Vladimir Turzhitsky3), Vishal Bali3), Keisuke Tobe3), Machiko Abe3),Anna Roberts2), Megan Metzger2), Jarod Baker2), Carmen La Rosa3), Jessica Weaver3), Paul Dexter2,4,5), Kun Huang2,5) (School of Engineering andTechnology, Purdue University, USA1); Regenstrief Institute, Inc., USA2); Center for Observational and Real-World Evidence, Merck & Co., Inc.,USA3); Eskenazi Health, USA4); School of Medicine, Indiana University, USA5))

Background: Chronic cough (CC) is cough lasting more than 8 weeks and affects around 10% of adults. It is associated with frequent health carevisits and poor quality of life. But little is known regarding use of anti-allergy medications in patients with chronic cough.Methods:We extractedtwo patient cohorts from the electronic health records (EHRs) of a large statewide academic system and a public county hospital. One cohort (CC)includes 25,881 patients with chronic cough identified through previously defined criteria, and the other cohort (Non-CC) includes 239,154 patientswith cough but did not meet the chronic cough criteria. We applied a novel Deep Multi-View clustering (DMVC) method on randomly selected16,348 CC and Non-CC patients with available diagnosis, medication and lab test records. Two clusters enriched with CC patients (8,650) and onecluster enriched with Non-CC patients (3,382) are identified. We analyzed the allergy related medication taken by CC and Non-CC patients withinthe clusters. The 33 drugs in category“cold/cough/allergy are considered as allergy related medication, which include drugs in different sub-classes, such as“Opioid Antitussive-Antihistamine”,“Non-Narc Antitussive-Decongestant-Antihistamine”and so on. Results: Univariate analysiswas performed for the comparison. Correlations between allergy-related medication taken by the two cohorts were tested. The results show thatthere are 29.72% CC patients took cold/cough/allergy medications, whereas there only 4.73% Non-CC patients took cold/cough/allergy medica-tions. There are 51.33% CC patients and 11.61% Non-CC patients took medications in the category“antihistamines”. The p values are <0.0001 forboth allergy related categories. Conclusion: Patients with CC took more allergy related medications than non-CC patients. More effective treat-ments are needed to better manage cough among CC patients. Source of funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.,Kenilworth, NJ, USA.

102

PosterSession

PE1-5 Burden of persistent chronic cough in adults in a large managed care organization

Deshaun Parris1), Robert Zeiger1), Michael Schatz1), Benjamin Hong2), Fagan Xie2), Vishal Bali1), Jessica Weaver1), Jonathan Schelfhout1),Wansu Chen2), Keisuke Tobe1) (Center for Observational and Real-World Evidence (CORE), Merck & Co. Inc., USA1); Departments of Allergy andResearch and Evaluation, Kaiser Permanente Southern California (KPSC), USA2))

Background: To compare demographics, comorbidities, and healthcare resource utilization (HCRU) between chronic cough (CC) patients withand without persistent CC (PCC). Methods: Using administrative pharmacy and HCRU data, we identified patients aged 1885 years with CC ofmore than 8 weeks in 2013-2016 with continuous health-plan enrollment and pharmacy coverage. A specialist-diagnosed CC group was identifiedusing a KPSC-specific CC encounter diagnosis code at an outpatient specialty care visit. Second, an event-diagnosed CC group was derived, re-quiring at least 3 cough-related events using natural language processing of clinical notes, ICD 9/10 cough diagnoses, and antitussives. Patientsdispensed angiotensin-converting enzyme inhibitor were excluded. PCC was defined for the specialist-diagnosed CC patients as a repeat CC spe-cific encounter diagnosis in the follow-up year at an outpatient specialty care visit. For the event-diagnosed CC patients, PCC required another 3events in the follow-up year. We compared patient characteristics and HCRU between CC patients with and without PCC in the baseline andfollow-up years. Results:We identified 50,163 patients with CC, of whom 8,970 (17.9%) had PCC. Compared to patients without PCC, patients withPCC evidenced significant (P<0.001) differences in both the baseline and outcome years with respect to (1) demographics: older age, lower house-hold income, more years of health-plan enrollment, and more Medicare enrollees; (2) comorbidities: higher Charlson comorbidity index and higherfrequency of asthma, gastroesophageal reflux disease (GERD), pneumonias, chronic rhinitis, chronic obstructive lung disease, upper airway coughsyndrome, cardiovascular disorders, anxiety, and depression; (3) HCRU: all cause and respiratory cause emergency department visits and hospi-talizations and 2 cough specialty department visits; (4) laboratory tests: more spirometry, chest and sinus imaging, laryngoscopy, esophageal endo-scopy; and (5) dispensed medications: more GERD drugs, asthma controllers, oral corticosteroids, antitussives, anxiolytics, and antidepressants.Conclusions: Patients with PCC evidenced higher disease burden than those without PCC.

PE1-6 Degree of skin moisture in allergic diseases varies according to complication of airway diseases

Shintaro Suzuki, Kuniaki Hirai, Yoshito Miyata, Megumi Jinno, Hideki Inoue, Shin Ohta, Tetsuya Homma, Akihiko Tanaka, Hironori Sagara (Divi-sion of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Showa University, Japan)

Background:Moisture is known to be an important component of human skin and to play a role in protection against various foreign substances.Therefore, past publications show that skin moisture (SM) is related with pathogenesis of some allergic diseases such as eczema, atopic dermatitis,and food allergy in childhood. Asthma frequently complicates with those diseases above, however the relationship between the major allergic air-way disease and the degree of skin moisture have not been well explored yet. The purpose of this research is the evaluation of degree of SM toexplore which the complication of asthma is related with skin status for the allergic patients in adult population. Methods: Subjects are patientsdiagnosed with food allergy, anisakis allergy, and asthma at Showa University Hospital (n=35, 32, 216, respectively). Twenty-four subjects diag-nosed with food allergy were also complicated with asthma (ACO was included). Degree of SM (SMD) was examined on the right forearm skin ofthe subjects with a skin moisture analyzer in the outpatient at the hospital. The subjects were divided into four groups based on both the main di-agnosed disease and the complication of asthma: anisakis allergy, food allergy, food allergy with asthma, asthma). The comparison of SMD wasperformed among those groups. Results: Mean age of the subjects was 52.3 years. Mean examined SMD is 19.6(%, an optional unit). The asthmagroup showed the lowest SMD (17.4%), and the value was particularly low in the elderly subjects (16.9%, <75 yo). The food allergy group showedlower SMD than the anisakis allergy group, despite younger age (21.1%, 50.3 yo vs 24.3%, 54.2 yo). Finally, the value for the food allergy withasthma group was extremely low (18.1%). Conclusion: Food allergy in adults might decrease skin protective status. Furthermore, such skin func-tion might be decreased further due to the complication of asthma.

PE1-7 Baseline characteristics from phase 3, randomized controlled trials (COUGH-1 and COUGH-2) of gefapixant, a P2X3 receptorantagonist, in refractory or unexplained chronic cough

David Muccino1), Masashi Kikuchi2), Alyn H Morice3), Surinder S Birring4), Lorcan McGarvey5), Peter V Dicpinigaitis6), Ian D Pavord7),Carmen La Rosa1), Christopher Assaid1), Jaclyn A Smith8) (Merck & Co., Inc., USA1); MSD K.K., Japan2); Hull York Medical School, UK3); Division ofAsthma, Allergy and Lung Biology, King’s College London, UK4); Centre for Experimental Medicine, Queen’s University Belfast, UK5); Albert Ein-stein College of Medicine and Montefiore Medical Center, UK6); Oxford NIHR Respiratory BRC, Nuffield Department of Medicine, University ofOxford, UK7); Division of Infection, Immunity and Respiratory Medicine, University of Manchester, UK8))

Background: There is an unmet need for medications for chronic cough that is refractory to treatment (RCC; cough persists despite treatmentfor diagnosed conditions associated with cough) or unexplained (UCC; no diagnosis is found). Phase 3 clinical trials of gefapixant, a P2X3 receptorantagonist, in patients with RCC or UCC have completed enrollmentMethods: COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are Phase3, randomized, placebo-controlled, double-blind, parallel-group trials to evaluate subjects 18 years of age, diagnosed with RCC or UCC (1 year), andwith 40 mm on the Cough Severity Visual Analog Scale (VAS). The primary efficacy study period is 12 (COUGH-1) AND 24 (COUGH-2) weeks. In-terventions include placebo, gefapixant 15 mg, or gefapixant 45 mg (1:1:1 ratio). Objective and subjective measures will be assessed; the primaryendpoint is 24-hour cough frequency (average frequency over 24-hours at Week 12 or 24). Results: COUGH-1 and COUGH-2 randomized andtreated 730 and 1314 patients, respectively; in COUGH-1/COUGH-2, 74%/75% are female, mean age is 59/58 years, mean body mass index (BMI) is28.24/28.78 kg/m2 and mean duration of cough is 11.5/11.1 years, and 59%/65% were diagnosed with RCC while 41%/35% were diagnosed withUCC. Regional distribution is Europe (50%/56%), N. America (23%/22%), Asia Pacific (14%/6.2%), and Other (13%/17%). The baseline demograph-ics were largely similar across regions. Conclusions: Preliminary baseline characteristics of patients randomized in COUGH-1 and COUGH-2 areconsistent with the demographics observed in other clinical studies of RCC/UCC. This global study will inform the efficacy and safety profile ofgefapixant in the treatment of patients with RCC and UCC.

103

PosterSession

PE1-8 Allergen avoidance clinical trial: correlation of symptom scores between 4 and 6 point scoring systems

Todor A Popov1), Grigoriy Garyuk2), Igor Kaydashev3), Svitlana Kharkivska4), Yasuo Ohashi5), Kimihiro Okubo6) (Department of Occupational Dis-ease, University Hospital Sv. Ivan Rilskipational, Bulgaria1); Private Enterprise Garyuk, Ukraine2); 1st City Clinical Hospital of Poltava City Coun-cil, Ukraine3); Medical Center “Family Health”, Ukraine4); Department of Integrated Science and Engineering for Sustainable Society, Chuo Uni-versity, Japan5); Department of Otorhinolaryngology, Nippon Medical School, Japan6))

Background: Allergic rhinitis is the most prevalent chronic non-communicable disease worldwide and clinical trials assessing different manage-ment options are increasingly underway. Standardization of outcome measures has become essential from regulatory and academic viewpointand position statements by international and national societies have proposed 4-point severity score for symptom assessment as current state-of-art. In a 2014 pivotal study proving the efficacy of powder methylcellulose (pMC) in patients with seasonal allergic rhinitis (SAR) we used a 6-levelseverity score to assess symptoms. As a transition to the 4-point scoring scale used in Japan, we now performed a similar study using both 4- and6-point scoring scales.Methods: In a double-blind, placebo-controlled, parallel-group clinical trial during 2019 we recruited 100 subjects with SARsensitive to grass pollens and randomized them to pMC (n=50, 29 women, age 36 years/median/, [18-59]/range/) or placebo (n=50, 24 women, age32.5 [18-61]) to be puffed in each nostril thrice daily for 28 days during the pollen season. Diary was kept for each patient using both 6-point scoring(1 to 6 for nasal congestion, rhinorrhea, sneezing, eye symptoms and lower airway symptoms) and 4-point scoring (0 to 3 for nasal congestion, rhi-norrhea, sneezing). Polycolic correlation coefficient seeking association between ordinal scales having different categories was computed. Subjectswere also asked if they felt to be in the active or placebo arms of the study (2-test). Results: There was strong statistically significant (P<0.001)correlation between the 6-point and 4-point severity scores: congestion (0.580 at baseline/0.569 after intervention), rhinorrhea (0.878/0.903) sneez-ing (0.934/0.929), and total nasal symptom scores (0.437/0.449). Subjects could predict with high probability whether they were in the active or pla-cebo arms of the study (P<0.0001). Conclusions: The study supports the feasibility of using 4-point severity score for allergic rhinitis ensuring con-tinuity to previous 6-point ordinal scoring. It also reconfirms the benefits of using pMC as a proxy to allergen avoidance measure in SAR.

PE1-9 Comparison of diffusion capacity and bronchodilator responsiveness testing in Vietnamese patients with persistent airway ob-struction

Tai Q Tran, Lan TT Le (Department of Respiratory Functional Exploration, Viet Nam)

Asthma and chronic obstructive pulmonary disease (COPD) are labeled for heterogeneous respiratory conditions. Differentiating between asthmaand COPD can be difficult, particularly in cases with persistent airflow obstruction. Low diffusion capacity of the lung with CO (DLCO) and nega-tive bronchodilator responsiveness testing (BRT) are lung function markers for COPD. In contrast, asthmatic patients usually have normal/highDLCO and positive BRT. The study aims to determine the characteristics of DLCO and BRT in patients with persistent airway obstruction and tocalculate the agreement between DLCO and BRT in the diagnosis of asthma and COPD. Data were collected from 120 Vietnamese subjects withrespiratory symptoms and acceptable spirometry, plethysmography, and DLCO results at University Medical Center Clinic 1 and CommunityHealthcare Center in Ho Chi Minh City, Vietnam from 2018 to 2020. There were 65 patients aged 42-90 years with persistent airway obstruction(pre and post-BRT FEV1/(F)VC < LLN), no restrictive defect (TLC > LLN). Low DLCO was diagnosed when DLCO < 80% predicted. Criteria forpositive BRT include a post-BRT increase in FEV1 or (F)VC≧12% and 200 mL, or PEF≧20%. According to the data, there were 27.69% (18/65)positive BRT and 83.08% (54/65) low DLCO in subjects with persistent airflow obstruction and normal/high TLC. Low DLCO accounted for87.23% (41/47) in negative BRT and 72.22% (13/18) in positive BRT. There was a slight agreement in the diagnosis of asthma and COPD with anobserved agreement of 70.77% (46/65) and kappa=0.17 (-0.08; 0.43). We have found a high proportion of reduced DLCO in cases with persistent air-way obstruction, with or without positive BRT. This prompts pulmonologists to use DLCO in addition to spirometry with BRT to avoid misdiag-nosing asthma and COPD.

PE1-10 Role of reactive persulfides in influenza A virus-induced oxidative stress

Tomohiro Ichikawa1), Katsuya Takita1), Hisatoshi Sugiura1), Tadahisa Numakura1), Takaaki Akaike2), Masakazu Ichinose1) (Department of Respiaro-try Medicine, Tohoku University, Japan1); Department of Environment Medicine and Molecular Toxicology, Tohoku University, Japan2))

Purpose of the Study: Influenza virus contributes to acute asthma exacerbation and oxidative stress play a role in the pathogenesis. The purposeof the study was to determine the role of reactive persulfides (RSS), recently identified endogenous antioxidant, on influenza A virus (IAV)-induced oxidative stress.Methods: Human bronchial epithelial cell line, BEAS-2B cells were exposed to polyinosinic:polycytidylic acid (poly (I:C)), atoll like receptor 3 agonist, or IAV strain H1N1 with or without RSS donor. Intracellular productions of RSS and reactive oxidative species (ROS)were measured using SSP-4, a specific fluorescent probe for RSS and CellRox dyes, respectively. Cell cytotoxicity, as measured by levels of lactatedehydrogenase (LDH) in the supernatant, was assayed using LDH Cytotoxicity Assay Kit. Results: Exposure to both poly (I:C) and H1N1 in-creased the ROS production in the cells. In contrast, SSP-4 intensities were reduced by the exposures. Pretreatment with the RSS donor restoredthe SSP-4 intensity and attenuated the poly (I:C)- or IAV- induced ROS production. LDH levels in the supernatant were increased by poly (I:C) andHIN1, which was attenuated by pretreatment with RSS donor. Conclusion: These data suggest that supplementation with RSS donor might be anovel therapeutic approach for IAV-induced exacerbation of chronic airway diseases by modulating oxidative stress.

104

PosterSession

PE1-11 Evaluation of mucus plugs and bronchial wall thickening on three-dimensional computed tomography in patients with unex-plained chronic cough whose sputum yielded filamentous basidiomycetes

Haruhiko Ogawa1), Kenichiro Okumura2), Yuichi Yoshie2), Takahiro Nadamura3), Kazuya Tone4), Noriyuki Ohkura5) (Department of Environmentaland Preventive Medicine, Kanazawa University, Japan1); Department of radiology, Kanazawa University Graduate School of Medical Sciences, Ja-pan2); Radiology Department, Ishikawa-ken Saiseikai Kanazawa Hospital, Japan3); Division of Respiratory Medicine, Jikei University School ofMedicine, Japan4); Respiratory Medicine, Kanazawa University Hospital, Japan5))

Background: Fungus-associated chronic cough (FACC) is a new clinical concept, which has recently been introduced into the 2019 Japanese Res-piratory Society guidelines for the management of cough and sputum, with the following manifestations: (i) chronic cough; (ii) the presence of envi-ronmental fungi, particularly filamentous Basidiomycetes (f-BM), in sputum; and (iii) a good clinical response to antifungal drugs. As patients withFACC do not have specific features on general investigation, a diagnosis of unexplained chronic cough (UCC) would be made without attempts todetect f-BM colonization in the airway. This study was performed to retrospectively review and analyze the tiny lesions of airways on three-dimensional CT and to evaluate the relationships between the calculated image data and the results of fungal cultures of sputum obtained fromUCC patients.Methods: UCC outpatients who had been given various questionnaires for cough, pulmonary function tests, and fungal cultures ofsputum were evaluated. Multi-detector-row CT (MDCT) was performed for three-dimensional CT analysis of the lungs. Retrospective analysiswas carried out with three groups: f-BM culture-positive group, other fungal culture-positive group, and culture-negative group. Results: Of the50 patients, three were excluded and the remaining 47 were included in the analysis. There were no significant differences in respiratory functionor clinical characteristics among the three groups. The common features on high-resolution CT (HRCT) included tree-in-bud (TIB) pattern, multi-ple centrilobular nodules, and bronchial wall thickening. Bronchiolar mucus plugs were detected in 14% of all cases. The bronchiole walls weresignificantly thicker when mucus plugs were found (P=0.010). Bronchiolar walls were the thickest and the score of mucus plugs was the highestin patients with f-BM culture-positive sputum (P=0.043). Conclusion: Imaging findings of f-BM culture-positive UCC patients include high mucusplug scores and bronchiolar wall thickening on three-dimensional CT. Our results reported here indicated the need to evaluate the possibility offungal colonization in the airway of UCC patients in clinical practice.

PE1-12 Blood eosinophils at the stable period are a biomarker of frequent exacerbation for Japanese patients with COPD

Yuki Kurihara, Hiroki Tashiro, Koichiro Takahashi, Hironori Sadamatsu, Tetsuro Haraguchi, Chiho Nakashima, Tomomi Nakamura,Naoko Aragane (Department of Respiratory Medicine, Saga University Hospital, Japan)

Background: Exacerbations are one of a critical events in chronic pulmonary obstructive disease (COPD). Frequency of COPD exacerbation is as-sociated with the prognosis including mortality, however useful biomarker is not fully established.Methods: The present study retrospectively in-vestigated 481 patients with COPD. Clinical features at stable period were compared between patients who experienced severe exacerbation (n=88, 18.3%) and those who never experience severe exacerbation (n=393, 81.7%). In the patients who experienced the exacerbation, clinical featureswere also compared between frequent exacerbator (Annual exacerbation rate at more than 2 times, n=27, 30.7%) and infrequent exacerbator (1time, n=61, 69.3%). Results: Compared to COPD patients who never experience exacerbation, body mass index, serum albumin, pulmonary func-tion were significantly lower and comorbidity ratio of cardiovascular disease, COPD assessment test score, modified medical research councildyspnea scale, treatment use of long-term oxygen therapy, treatment with long acting β2 adrenergic agonist, inhaled corticosteroid and macrol-ide were significantly higher in COPD patients with exacerbation (p<0.01, respectively). In patients who experienced exacerbation, frequent exac-erbators were significantly lower % forced expiratory volume in 1.0 second and higher risk of critical exacerbation, blood eosinophil, history of me-chanical ventilation use, treatment of long-term oxygen therapy and macrolide use than infrequent exacerbators (p<0.01, respectively). In multi-variate analysis, blood eosinophil is the most correlated parameter for exacerbation frequency (β value [95% confidence interval] 1.44 [1.11 1.86], p<0.01) and it is significantly correlated to annual exacerbation rate (R2=0.0614, p=0.02). Conclusion: Blood eosinophil at the stable period is themost correlative factor for frequency of severe exacerbation.

PE1-13 The disease burden and quality of life of chronic cough patients in Japan

Takekazu Kubo1), Keisuke Tobe2), Kotoba Okuyama1), Masashi Kikuchi3), Chen Yirong5), Schelfhout Jonathan4), Machiko Abe2), Shigeru Tokita1)

(Medical Affairs, MSD K.K., Japan1); Market Access, MSD K.K., Japan2); Clinical Research, Japan Development, MSD K.K., Japan3); Outcomes Re-search, Merck & Co., Inc., USA4); Health Division, Kantar, Singapore5))

Background: This study utilized a population-based online quantitative survey to compare chronic cough (CC) patients’ health-related quality oflife (HRQoL), work productivity and activity impairment (WPAI), and healthcare resource utilization (HRU) with matched controls currently notsuffering from cough. Methods: Respondents above 20-years-old who completed the 2019 Japan National Health and Wellness Survey (NHWS)were invited to participate in the online quantitative CC survey if they fulfilled the inclusion criteria. Controls without cough were selected fromthe NHWS by 1:4 propensity score matching. HRQoL, WPAI, HRU and experience of anxiety, depression and sleep problems were compared bymultivariable analyses after matching. The association between these outcomes and CC severity assessed by visual analogue scale was also con-ducted using multivariable models. All multivariable analyses adjusted for age, gender and adapted Charlson Comorbidity Index (CCI) which re-moved chronic pulmonary disease from the usual CCI. Results: Among the 26,043 respondents, 568 with current experience of CC and 2,272matched controls without cough were included in the analyses. The average CC patient was 56.0 years (SD=15.2), male (61.1%), employed (55.6%)with an adapted CCI of 0.23 (SD=0.55). CC patients had lower HRQoL in terms of physical component score (49.1 vs. 52.0, p<0.001), mental compo-nent score (46.3 vs. 49.2, p<0.001), and SF-6D health utility score (0.72 vs. 0.77, p<0.001) compared to controls. CC patients had greater work pro-ductivity impairment (25.1% vs. 18.0%, p<0.001) and more visits to healthcare practitioners (7.1 vs. 4.9, p<0.001) than controls. CC patients moreoften experienced anxiety (3.6% vs. 1.4%, p<0.001), depression (6.9% vs. 3.3%, p<0.001) and sleep problems (66.8% vs. 49.1%, p<0.001). Patients withmore severe CC showed significantly poorer scores in some HRQoL and WPAI measures relative to milder CC patients. Conclusion: This studygenerated novel real-world information showing that CC patients in Japan have significantly worse health outcomes, and increased WPAI andHRU compared to controls. These results provide valuable insights for understanding of the burden of the disease and future treatment develop-ment for this group of patients.

105

PosterSession

PE1-14 Roles of sensitization to staphylococcal enterotoxin in patients with bronchiectasis

Chie Morimoto, Hisako Matsumoto, Tsuyoshi Oguma, Susumu Sato, Isao Ito, Mariko Kogo, Natsuko Nomura, Noriyuki Tashima,Hironobu Sunadome, Toyohiro Hirai (Department of Respiratory Medicine, Graduate School of Medicine Kyoto University, Japan)

Background: Sensitization to Staphylococcal enterotoxin (SE) is associated with airflow limitation and smoking history in asthma. However, itsrole in bronchiectasis, wherein sensitization to aeroallergens is often observed and pathological bacteria including Staphylococcus aureus (S.aureus ) tends to colonize, remains unknown. Aims: To clarify a role of sensitization to SE in bronchiectasis, particularly in an association with S.aureus colonization in lower airway and with severity of bronchiectasis. Methods: In this retrospective, single center study, we examined pa-tients with bronchiectasis, irrespective of the presence of concomitant asthma, determined based on the chest computed tomography finding[modified Reiff (mReiff) score≧1]. Associations of sensitization to SE with clinical indices including sputum culture results were analyzed. Associa-tions between severity of bronchiectasis and clinical indices including pulmonary function and bacteria in sputum were also analyzed. Results: In45 patients (mean 71 years old, 35 females), frequency of sensitization to SE was 18%. Sensitization to SE was significantly associated with highertotal IgE level. S. aureus was detected in 37% of patients and its detection was significantly associated with sensitization to SE (p=0.04). Pseudo-monas aeruginosa (P. aeruginosa ) was detected in 40% of patients, but its detection was not associated with sensitization to SE. MReiff score,which was negatively correlated with %FEV1, was the highest in patients with P. aeruginosa only, followed by those with P. aeruginosa and S.aureus , neither of the bacteria, and S. aureus only in this order, with significant difference among the 4 groups. MReiff score was unrelated to sen-sitization to SE. Conclusion: Sensitization to SE may be associated with lower airway colonization of S. aureus in patients with bronchiectasis.However, its role in the severity of bronchiectasis may be limited.

PE1-15 dsRNA and staphylococcal enterotoxin B induces opposite inflammatory reactivity in epithelial cell

Jun-Pyo Choi1), Kyung-Min Ahn2), Purevsuren Losol1,3), Yong-Hyun Kim1,2), Sae-Hoon Kim1,2,3), Sang-Heon Cho2), Yoon-Seok Chang1,2,3) (Department ofInternal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea1); Department ofInternal Medicine, Seoul National University College of Medicine, Republic of Korea2); Institute of Allergy and Clinical Immunology, Seoul NationalUniversity Medical Research Council, Republic of Korea3))

Background: Epithelial cells is known as a structure cell in the lung and it is first cell that meet foreign molecules with macrophage. Although,epithelial cell is non-immune cells, this cell also plays an important role in innate immune system via induction of cytokines including interferon,and diverse chemokines. In addition, recently, the importance of epithelial cell was highlighted because of production ability of IL-25, 33, and TSLPwhich are able to activate innate lymphoid cell 2. Owing to the ability of epithelial cell to produce various cytokines, we stimulated epithelial cellwith foreign molecules, dsRNA and bacteria toxin, in this experiment to evaluate responses according to stimuli.Methods:We stimulated BEAS2B cells with poly I:C (1 to 100 ug/ml, 10 fold scale) or S. aureus enterotoxin B (SEB, 2 and 20 ug/ml)) after overnight starvation with serum free me-dia. Next, we collected supernatant at 4 time points (0.5, 3, 6 & 12h) and evaluated 14 kinds of cytokines (IL-6, 33, TSLP, TNF-alpha, IFN-beta,lambda, CCL2, 3, 5, CXCL8, 10, 11, ICAM-1 & G-CSF) with ELISA. Results: Both stimuli showed positive proportion of cytokine production bydose, but did not pattern difference by dose. Among 14 cytokines, Poly I:C induced 10 kinds (IL-6, IFN-beta, lambda, CCL2, 3, 5, CXCL8, 10, 11 andICAM-1) from 3 or 6 hour after stimulation. Especially, IFN-lambda, CXCL8 and CCL2 were detected in early time and increased rapidly. Com-pared to poly I:C stimulation, however, SEB stimulation into epithelial cell showed low reactivity. Most of cytokines were not detected or detectedat low level. Interestingly, CCL2 was elevated enormously, unlike other cytokines. Conclusion: Epithelial cell shows considerable reactivity todsRNA via induction of various cytokine induction. However, SEB stimulation to epithelial cell shows very low reactivity compared to dsRNAstimulation.

PE1-16 THP-1 derived macrophage shows different responses to polyI:C and staphylococcal enterotoxin

Jun-Pyo Choi1), Purevsuren Losol1,2), Yong-Hyun Kim1,3), Sae-Hoon Kim1,2,3), Sang-Heon Cho2,3), Yoon-Seok Chang1,2,3) (Department of Internal Medi-cine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea1); Institute of Allergy andClinical Immunology, Seoul National University Medical Research Council, Republic of Korea2); Department of Internal Medicine, Seoul NationalUniversity College of Medicine, Republic of Korea3))

Background: Airway inflammation can be induced by inhalable diverse molecules including virus and bacteria. These microorganisms can be de-rived from outside of our body or inside of upper-respiratory tract as commensal bacteria. They have various PAMP molecules which can induceactivation of innate immune responses resulted in airway inflammation. In this study, to study the responses to microorganism derived moleculesin macrophage at the frontline of airway defense, we stimulated THP-1 derived macrophage with diverse doses of double-stranded RNA (polyI:C)and bacteria derived toxin.Method: To differentiate macrophage from THP-1 cells, we treated PMA to THP-1 cells. After induction of differentia-tion, we incubated cells at serum-free media for overnight to exclude the effect from serum component and activation by PMA. After starvation,we stimulated various doses of poly I:C (1, 10 and 100 ug/ml) and S. aureus enterotoxin B (SEB, 2 and 20 ug/ml) and evaluated the expression ofcytokines in culture supernatants with ELISA (14 kinds; IL-6, 33, TSLP, TNF-alpha, IFN-beta, lambda, CCL2, 3, 5, CXCL8, 10, 11, ICAM-1 & G-CSF)at different time-points. Results: There was difference of production by dose of dsRNA, however, difference of expression pattern was not ob-served. DsRNA induced production of enormous 9 kinds of pro-inflammatory cytokines (IL-6, TNF-alpha, CCL2, 3, 5, CXCL8, 10, 11, ICAM-1), andthey were detected from 3 or 6 hours after stimulation. In the case of SEB, in addition to above cytokines, IFN-beta, IL-33 and TSLP were inducedfrom early time after stimulation. Furthermore, IL-8 and ICAM-1 were rapidly and more induced by SEB stimulation. However, SEB showedweak responses in the production of other chemokines compared to dsRNA stimulation. Conclusion: Among 14 cytokines we evaluated, dsRNAstimulation induced enormous chemokine and professional pro-inflammatory cytokines, on the other hand, SEB induced moderate chemokine pro-duction with IFN-beta, IL-33, TSLP and ICAM-1.

106

PosterSession

PE1-17 Complication of malignancy in patients with allergic bronchopulmonary aspergillosis

Hiroki Kawabata, Kanako Hara, Yosuke Chiba, Kazuhiro Yatera (Department of Respiratory Medicine, The University of Occupational and Envi-ronmental Health, Japan)

Background: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by type I and type III hypersensi-tivity reaction to Aspergillus species colonizing in the lower respiratory tract, and airway eosinophilic inflammation induces mucus plug and cen-tral bronchiectasis. Bronchial asthma and cystic fibrosis are common underlying diseases of ABPA and systemic corticosteroids are often neededto inhibit lung destruction. In East Asia, patients with older onset of ABPA accompanied with older onset of bronchial asthma and low serum IgElevels have been reported. We recently experienced two ABPA patients that were concurrently complicated with cancer and also showed spon-taneous remissions of ABPA after surgical resections. Complication with cancer and ABPA have not been reported so far, and we conducted aretrospective cross-sectional single center study to clarify the associations between ABPA and malignancy. Methods: This was a single-centerretrospective study conducted with patients who visited to the university hospital of The University of Occupational and Environmental Health,Japan from January 2000 to April 2020 and diagnosed with ABPA who met The International Society for Human and Animal Mycology (ISHAM)ABPA criteria. Results: A total of 13 patients were enrolled, and their mean age of the onset of ABPA was 62.5 years. Two patients (15.4%) exhib-ited low levels of serum total IgE (<500 IU/mL). During the clinical course, the recurrence of ABPA after initial treatment was observed in 6(46.2%) cases. Patients developing ABPA over 60 years of age accounted for 69.2% of the cases and was associated with never smoking (p=0.003),short duration between the onset of asthma and ABPA (p=0.0199), and delayed onset of asthma (p=0.0028). Complication with malignancy ac-counted for 46.2% (6/13), and subsequent ABPA after diagnosing malignancy within three years were seen. Among them, cervicothoracic malig-nant regions were seen in 83.3% (5/6) and one patient without cervicothoracic diseases had traction bronchiectasis secondary to idiopathic pulmo-nary fibrosis. Conclusions: Cervicothoracic malignant regions may be related with late onset of ABPA.

PE1-18 Investigation of the number of oral bacteria and the conditions of asthma, COPD, and ACO

Toshiya Inui1), Yukiko Abe1), Tatsuya Shirai1), Kouzo Suhara1), Maya Tsuchiya1), Takayasu Watanabe1), Mitsuru Sada1), Atsuto Mouri1),Shinkichi Iwanari2), Mitsuhiro Kamimura1) (Pulmonology Department, National Hospital Organization Disaster Medical Center, Japan1); Depart-ment of Oral and Maxillofacial Surgery, National Hospital Organization Disaster Medical Center, Japan2))

Background: Neutrophilic airway inflammation has been suggested to play a crucial role in chronic inflammatory airway diseases such as chronicobstructive pulmonary disease (COPD) and severe bronchial asthma, and airway epithelial cells are involved in the response to bacteria in the res-piratory tract. However, bacteria found in the oral cavity, a part of the upper respiratory tract, and their presence suggests infections of the air-ways. We investigated the number of oral bacteria present in the conditions of asthma, COPD, and asthma-COPD overlap (ACO). Methods: Weanalyzed the correlation between the number of oral bacteria and various clinical data of 18 patients with asthma, 19 with COPD, and 20 withACO whose condition was stable and who visited our center from August 2019 through March 2020. This study was approved by our institution,and written informed consent was obtained from each patient. We measured the number of oral bacteria using the dielectrophoretic impedancemeasurement method. Results: In the patients with asthma, the number of oral bacteria correlated significantly negatively with the respiratoryfunction tests of %FEV1, %MMEF, and %V25 but did not correlate significantly with ACT and FeNO. In addition, in the patients with COPD, thenumber of oral bacteria correlated significantly negatively with the respiratory function tests of VC, FVC, FEV1, %FEV1, MMEF, PEF, %PEF,and V50 but not with CAT. In contrast, there was no significant correlation between the number of oral bacteria and any of the clinical data in thepatients with ACO. Conclusions: These results suggested that the number of oral bacteria was associated with lung capacity and airflow obstruc-tion in the patients with COPD and with airflow obstruction in the patients with asthma. However, we found no relation between the number oforal bacteria and symptoms or FeNO. Further studies are needed.

PE1-19 Anti-Aspergillus fumigatus response in stable patients with bronchiectasis

Kateryna Gashynova, Kseniia Suska, Valeriia Dmytrychenko (Department of Occupational Diseases and Clinical Immunology; State InstitutionDnipropetrovsk Medical Academy of the Ministry of Health of Ukraine, Ukraine)

Patients with bronchiectasis (B) are at the high-risk group for allergic bronchopulmonary aspergillosis (ABPA), besides Aspergillus fumigatus(AF) is widely distributed in the environment. Increase of the specific IgG4 to AF (sAfIgG4) is known to be the one of the ABPA markers. On theother hand, production of the sAfIgG4 could be one of the antifungal defense mechanisms. The study aimed to measure sAfIgG4 in stable patientswith B without ABPA.Methods: The study included stable patients with confirmed B according to HRCT. Patients with any previous history oractive ABPA and diagnosed asthma were excluded. Weight were measured by“Body composition monitor Omron BF511”for the static weigh-ing and body mass index (BMI) was calculated. sAfIgG4 to recombinant (rAspf1) AF allergens was measured with Thermo Fisher ImmunoCAP.Microbiological detection of sputum samples were conducted by conventional bacteriological methods. Results: 25 patients were included (aver-age age 56 (41;64) years, 10 men (40%)). sAfIgG4 responses were detected in all patients from 0.05 to 0.87 kU/l, median level 0.12 (0.07;0.12) kU/l.We detected, that the level of sAfIgG4 was higher in patients with normal weight (18.5BMI<25 kg/m2, n=12), than in patients with overweight(BMI25 kg/m2, n=13) 0.11 (0.09;0.165) kU/l against 0.05 (0.02;0.12), p=0.023. 17 patients (68%) produced sputum: eight samples (47.1%) were colo-nized by Pseudomonas aeruginosa , three (17.6%) by Haemophilus influenza , one (5.9%) by Streptococcus pneumoniae , one (5.9%) by Candida albi-cans and four patients (23.5%) did not have pathogens in sputum. None of samples was colonized by AF . Conclusions: Every patient with stableB and without any history of ABPA had elevated levels of AfIgG4 which probably indicates the chronic colonization by AF , although there wasno detected any AF positive sample during conventional bacteriological methods. This response was higher in patients with normal weight.Based on this data, we recommend further investigations of the sAfIgG4 level in all patients with B even without ABPA, focusing on patients withdifferent from normal BMI.

107

PosterSession

Poster Session 2Adult asthma 1

PE2-1 Clinical usefulness of fractional exhaled nitric oxide measurement for diagnosing prolonged cough in daily practice

Masaki Hanibuchi, Atsuro Saijo, Atsushi Mitsuhashi (Department of Respiratory Medicine, Shikoku Central Hospital of the Mutual aid Associationof Public School Teachers, Japan)

Objective: Prolonged cough is one of the troublesome symptoms commonly seen in clinical practice. Cough variant asthma (CVA), postinfectiouscough (PIC) and atopic chough (AC) are the major causes of prolonged cough in Japan, but their differential diagnosis is somewhat difficult. Theutility of fractional exhaled nitric oxide (FeNO) measurement in the differential diagnosis of prolonged cough has been reported. NIOX VERO+

(NOV) is a new device that will replace NIOX MINO+. Because NOV has not been used for many years in clinical practice, its diagnostic utility hasnot been fully elucidated. In this study, the performance of NOV for FeNO measurements was determined. Methods: We retrospectively ana-lyzed 243 consecutive patients complaining prolonged cough. FeNO, pulmonary function tests, IgE, and eosinophils in peripheral blood weremeasured. Final diagnoses were made according to the Japanese Respiratory Society criteria. The study protocol was approved by the Institu-tional Review Board of our institution. Results: Among 243 patients complaining prolonged cough, 156 (64.2%) were female. The mean age was52.6 years and the mean duration of cough was 8.1 weeks. CVA was diagnosed in 74 patients (30.5%), PIC in 52 (21.4%), and AC in 24 (9.9%). FeNOlevels measured by NOV were significantly higher in CVA (36.6±24.3 ppb) than in PIC (15.6±7.7 ppb), AC (17.9±9.9 ppb) and others (16.6±8.5ppb) (p<0.05). The optimal cut-off for distinguishing CVA from PIC, AC and others was 23.0 ppb (sensitivity 85.1%, specificity 81.1%, area underthe curve 0.87). Conclusions: FeNO measured by NOV could be used as a diagnostic marker of prolonged cough, especially for the differential di-agnosis CVA from PIC, AC and others.

PE2-2 Analysis of the frequency and interest of tweet including “asthma” and “attack” in Japanese twitter users

Tomomi Ichikawa1), Takahiro Hirai1), Zenta Seto2), Akihiro Moriyama1), Seisuke Okazawa2) (Toyama Red Cross Hospital, Japan1); University ofToyama, Japan2))

Background: Posts to the microblogging service on Twitter, tweets contain personal information, perceptions, value judgments, and other medi-cal information such as health status. The objective of this study is to address the frequency of asthma attacks and the interests of tweet users inJapan.Method: Using the Twitter API from November 20, 2017, to March 4, 2019, we collected tweets containing both“asthma (ZENSOKU)”and

“attack (HOSSA)”in Japanese word (upper letter) once a week. The acquired tweets were analyzed using natural language processing librariesincluding artificial intelligence to elucidate the frequency and semantic analysis. For analysis, the julia language was used, and SudachiPy andgensim library were imported by PyCall. Result:We collected 144,469 tweets in 479 days. After removing duplication and ReTweet, 62,645 tweetswere included in the analysis. The frequency of tweets gradually increased from autumn to winter. The frequency of tweets was highest on Mon-day. In the nouns,“cough”,“medicine”,“hospital”,“common cold”and“inhalation”appeared most frequently used (the frequency were 7,869,5,337, 5,189, 4,172 and 3542 times, respectively). The analysis using Word2Vec, a deep learning processing showed that“hyperbreathing”,“dysp-nea”,“panic”,“inflammation”or“adverse effects”, etc. (the Cosine similarity were 0.573, 0.573, 0.554, 0.551, and 0.544, respectively) were used aswords with hight similarity to“asthma”and“attack”. Conclusion: Using artificial intelligence, we were able to extract health information, recog-nition, and value judgment from the user’s perspective from tweets related to asthma attacks. By adding semantic analysis, etc., it may be possi-ble to extract more abundant information.

PE2-3 The characteristics of refractory asthma who required admission for asthma exacerbation

Tomoya Harada, Ryohei Kato, Miki Takata, Ryota Okazaki, Akira Yamasaki (Department of Respiratory Medicine and Rheumatology, TottoriUniversity Hospital, Japan)

Background: The aim of this work is to analyze the relationship between blood eosinophil count and hospital admission in patients with refrac-tory asthma. Methods: A review was retrospectively carried out on all patients who admitted to our hospital due to asthma exacerbation be-tween January 2013 and December 2018. We defined refractory asthma as that who required long-term oral corticosteroid or biologics. Results:We identified 102 patients and 177 events of admission. Refractory asthma was included 19 patients and 57 events. Refractory group was elder,higher BMI, lower number of current smokers, higher frequency of aspirin exacerbation respiratory disease, sinusitis, and lower blood eosinophilcount than non-refractory group. Furthermore, the frequency of severe asthma exacerbation was lower in refractory group (p<0.001). Twentypercent of refractory asthmatic patients who were administered systemic corticosteroid at admission had over 150 cell/L of blood eosinophilcount. Asthma-COPD overlap is associated with elevated eosinophil in refractory group (p=0.016). Conclusion: Refractory asthma is associatedwith lower incidence of severe asthma exacerbations and lower blood eosinophil count. Asthma-COPD overlap may be difficult to decrease eosino-phils even administration of systemic corticosteroid.

108

PosterSession

PE2-4 Analysis of elderly asthma in Japan using NHOM-asthma data

Maho Suzukawa1), Hiroya Hashimoto2), Hiroyuki Tashimo1), Yoshitaka Oyamada3), Mari Miki4), Mitsumasa Ogasawara5), Yoshikazu Inoue6),Akiko Saito2), Ken Ohta1,7) (Clinical Research Center, National Hospital Organization Tokyo National Hospital, Japan1); Clinical Research Center,National Hospital Organization Nagoya Medical Center, Japan2); Department of Pulmonary Medicine, National Tokyo Medical Center, Jordan3);Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Japan4); Department of Respiratory Medi-cine, National Hospital Organization Osaka National Hospital, Japan5); Clinical Research Center, National Hospital Organization Kinki-Chuo ChestMedical Center, Japan6); Anti-Tuberculosis Association, Fukujuji Hospital, Japan7))

The prevalence of elderly asthma is rising in Japan as the population ages. We performed an analysis to compare the characteristics of elderly-asthma patients and non-elderly-asthma patients using data from a nation-wide prospective cohort study of asthma, NHOM-Asthma. We analyzeda total of 1,924 asthma patients, including 1,037 patients older than 65 years defined as elderly-asthma patients, who were recruited between July2017 and September 2018. The elderly-asthma patients showed a significantly later onset of asthma, were more non-atopic, showed a higherBrinkman Index and had fewer pets compared to the non-elderly-asthma patients. The elderly-asthma patients more frequently had comorbidi-ties such as COPD, hypertension, diabetes, heart disease, stroke and otitis media, but less frequently had other allergic diseases, aspirin-inducedasthma and mental disorders. The elderly-asthma patients showed lower lung function as assessed by flow-volume curves, and more severe smallairway obstruction when assessed with an impulse oscillation system. There were no differences in FeNO, the peripheral blood eosinophil countor total IgE. The asthma treatment steps did not differ between the groups, although the dose of inhaled corticosteroid used for elderly asthmawas more often a medium dose compared to lower or higher doses for non-elderly asthma. The use of anti-histamines and allergen immunother-apy were less frequent in the elderly-asthma patients, whereas the use of LAMA tended to be more frequent. Based on the questionnaires, theelderly-asthma patients showed significantly higher scores in ACQ and ASK-20, although there was no difference in the AQLQ scores. Forasthma control, the elderly-asthma patients had less frequent unscheduled hospital visits, but more frequent hospital admissions. In conclusion,there were clear differences in the disease characteristics, i.e., comorbidities, lung function, treatment, disease control, and adherence, betweenelderly-asthma patients and non-elderly asthma patients. Thus, elderly-asthma patients need to be managed differently from non-elderly-asthmapatients.

PE2-5 Complication rates of sleep apnea syndrome in complication rates of sleep apnea syndrome in bronchial asthma - usefulness ofESS -

Naoto Watanabe1,2), Sohei Makino2), Yoichi Nakamura1) (Medical Center for Allergic and Immune Disease Yokohama City Minato Red Cross Hospi-tal, Japan1); Tokyo Allergy and Respiratory Disease Institute, Japan2))

Background: Adult bronchial asthma (BA) is a risk factor for obstructive sleep apnea (OSAS) according to the Wisconsin Sleep Cohort study.Purpose: To determine complication rates of sleep apnea syndrome (SAS) with BA, and whether the Epworth sleepiness scale (ESS) question-naire is useful for SAS screening. Participants: This study included 193 outpatients with BA (average age, 56 years; range, 15-92 years; male, n=62; female, n=31) who provided written informed consent to undergo all procedures associated with the study.Methods: Patients who scored > 11on the ESS questionnaire underwent simple polysomnography (PSG). We explained the need for detailed examinations to patients with an apnea-hypopnea index (AHI) > 10 on the simple PSG, and referred them to a facility where they could undergo the precise PSG test. Patients with AHI >20 according to precise PSG results were treated using continuous positive airway pressure (C-PAP) or a mouthpiece. Results: 1. About 20% of pa-tients had ESS scores > 11. 2. The AHI increased in the simple PSG test when the ESS score was > 11. 3. The rate of weight gain > 10 kg washigher when ESS scores were > 11. 4. The rate of SAS complications was high among patients with BA and allergic rhinitis. 5. Sleep apnea syn-drome (AHI>5) was suspected in 70% of patients who underwent simple PSG. 6. About 5% of all patients were treated for SAS. 7. All patientstreated for SAS had AHI>30 in simple PSG. Considerations: Scores > 11 in the ESS questionnaire are an indication to undergo simple PSG. Therate of SAS complications in patients with BA is about 30%, and these complications are associated with BA exacerbation and heart disease com-plications. Thus, aggressive scrutiny and faster induction of therapy is desirable. The ESS questionnaire is useful for SAS screening.

PE2-6 Impact of coexisting COPD on mortality in patients with corticosteroid-dependent asthma

Sang-Heon Kim, Joon Kyung Kim, Jee Yea Choi, Sung Jun Chung, Hyun Lee, Dong Won Park, Jang Won Sohn, Ho Joo Yoon (Department of Inter-nal Medicine, Hanyang University College of Medicine, Republic of Korea)

Background: Chronic corticosteroid (CS) use is a risk factor for long-term mortality in asthma patients, and the presence of coexisting chronic ob-structive pulmonary disease (COPD) is associated with a severe presentation and poor prognosis. However, the impact of coexisting COPD onlong-term mortality in patients with CS-dependent asthma has not been well elucidated. This study aimed to determine the impact of coexistingCOPD on long-term mortality in patients with CS-dependent asthma. Method: A retrospective cohort of CS-dependent asthma patients aged 40years or older was established using records from the Korean National Health Insurance Service database for 2005 to 2015. We classified the sub-jects into two groups according to the presence of COPD and evaluated the hazard ratio (HR) for all-cause mortality in patients with COPD rela-tive to those without COPD. Results: Of 8,021 patients with CS-dependent asthma, 3,121 (38.9%) had COPD. All-cause mortality was significantlygreater in CS-dependent asthma patients with COPD than in those without COPD (9,955/100,000 person-years vs. 5,585/100,100 person-years, P<0.001). The adjusted HRs were 1.29 (95% confidence interval [CI], 1.21-1.38), and the associations were especially significant for chronic lower respi-ratory diseases (subdistribution HR 2.30, 95% CI, 2.06-.57) and lung cancer (subdistribution HR 1.34, 95% CI: 1.02-1.78). Conclusion: In thispopulation-based retrospective cohort study, the presence of physician-recognized COPD was associated with greater all-cause mortality andgreater risk of mortality due to chronic lower respiratory diseases and lung cancer in patients with CS-dependent asthma. This study was fundedby the Korea Ministry of Environment (MOE) as the Environmental Health Action Program (2016001360003).

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PosterSession

PE2-7 Decline of lung function in adults with a history of childhood asthma

Shinichiro Miura1), Hiroshi Iwamoto1), Keitaro Omori2), Kakuhiro Yamaguchi1), Shinjiro Sakamoto1), Yasushi Horimasu1), Takeshi Masuda1),Shintaro Miyamoto1), Taku Nakashima1), Kazunori Fujitaka1), Hironobu Hamada1), Akihito Yokoyama3), Noboru Hattori1) (Department of Molecularand Internal Medicine, Institute of Biomedical & Health Sciences, Hiroshima University, Japan1); Department of Infectious Diseases, HiroshimaUniversity, Japan2); Department of Hematology and Respiratory Medicine, Kochi University, Japan3))

Background:We previously reported that clinically remitted childhood asthma is a significant risk factor for airflow obstruction in cross-sectionalstudy. However, longitudinal change of lung function in adults with a history of remitted childhood asthma has not been clarified. The aim of thisstudy was to examine whether clinically remitted childhood asthma is a risk factor for rapid decline of lung function and developing airflow ob-struction.Methods: Participants from five healthcare centers were included in the study. We evaluated the lung function of participants who un-dergo spirometry and answer self-administered questionnaires between 2007 and 2017 at least twice and the interval between the first and finalassessments was longer than 24 months. Participants with a history of lung disease other than childhood asthma were excluded. Results: A totalof 4050 participants were analysed. The mean age was 48.2 years, and the mean follow-up periods were 5.0 years. Among the 4050 participants,145 participants had a history of remitted childhood asthma. The baseline percent predicted FEV1 were significantly lower in the participantswith remitted childhood asthma than in healthy controls (94.1±1.1% and 97.9±0.2%, P<0.001). In the longitudinal analysis, decline of FEV1 wassignificantly greater in the participants with remitted childhood asthma when compared with healthy controls (-31.1±5.5 ml/year and -17.9±1.1ml/year, P<0.05). In the participants with normal lung function at the first assessments (FEV1/FVC 70%), the participants with remitted child-hood asthma developed airflow obstruction more frequently than healthy controls during the follow-up period (6.6% and 3.1%, P<0.05). Multivari-ate analyses revealed that a history of remitted childhood asthma was independently associated with rapid decline of FEV1 and was significantrisk factor for the development of airflow obstruction. Conclusion: A history of childhood asthma, even when it is clinically remitted, is a signifi-cant risk factor for rapid decline of FEV1 and developing airflow obstruction in adults.

PE2-8 Variability in airway responsiveness assessed by the astograph method

Mari Miki, Kiyoharu Fukushima, Yuji Yamamoto, Takanori Matsuki, Yohei Oshitani, Hiroyuki Kagawa, Kazuyuki Tsujino, Keisuke Miki,Hiroshi Kida (Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Japan)

Background: Bronchial asthma (BA) is a chronic inflammatory disease characterized by airway hyperresponsiveness, which is specifically evalu-ated by testing the airway responsiveness. No study has investigated the oxygen saturation indices and tidal volume (VT) obtained during airwayresponsiveness tests. Methods: Forth-one patients with BA and cough variant asthma (CVA) who tested positive on airway responsiveness as-sessments conducted between January 2018 and June 2019 were evaluated. Changes in the oxygen saturation (SpO2) and VT were estimatedwith the Astograph method, which investigated airway hyperresponsiveness with continuous methacholine inhalation. Results: All patients weredivided into four groupsSpO2/VT decreased group (both SpO2 and VT decreased during the testing; 10/42; 24%); SpO2 decreased group (onlySpO2 decreased; 8/42; 19%); VT decreased group (only VT decreased; 9/42; 21%); and SpO2/VT maintained group (both SpO2 and VT were main-tained; 14/42; 33%). No significant differences were observed among the groups for the following: 1) Dmin, the index of hyperresponsiveness; 2)SGrs/Grs count, an indicator of airway responsiveness; 3) each respiratory impedance, which was evaluated by the forced oscillation technique us-ing a Mostgraph-01; and fraction of exhaled nitric oxide (FeNO). However, SpO2/VT decreased group indicated a short illness duration (average22.3 months) and good FEV1% (average 86.2%) compared with the SpO2/VT maintained group (179.7 months p=0.0026, 75.7% p=0.0092, respec-tively). SpO2 decreased group showed relative short illness duration (47.3 months), lower FEV1% (75.3%, P=0.011) and higher V50/V25 (5.29, p=0.030) than those of SpO2/VT decreased group. These results might indicate that the condition of patients in the SpO2/VT decreased group hadnot progressed to bronchial wall remodeling and have enough reactivity of central and peripheral airway. Conclusion: The airway hyperrespon-siveness levels and oxygen desaturation are independent factors in patients with asthma. Astograph method-based early diagnosis of asthma mayhelp in improving the early asthmatic symptoms, thereby preventing the future remodeling of the bronchial walls.

PE2-9 Utility of R5-20 of MostGraph for outpatients of adult asthma in a clinic

Kan Kato1,2,3), Hiroshi Tanaka3) (Department of Internal Medicine, Tokyo Kensei Hospital, Japan1); Department of Internal Medicine, OoizumiHealth Cooperative Hospital, Japan2); Sapporo Cough Asthma and Allergy Center, Japan3))

Background:We have shown the usefulness of reversibility test of MostGraph’s measurement R5 after inhaled bronchodilator in the diagnosis ofcough variant asthma. R5-20 represents the frequency dependence of respiratory resistance, and it is said that R5-20 reflects the unequal ventila-tion in adults. So this time we considered the clinical utility of R5-20 for outpatients of adult asthma.Methods: The subjects were the 622 patientsat Idaimaeminamiyojo Clinic in Sapporo who underwent bronchial reversibility test with salbutamol by using MostGraph. We divided them into 3groups; 156 asthma patients (Group BA), 237 cough variant asthma patients (Group CVA), 229 allergic rhinitis patients without asthma (GroupAR), and examined their lung functions, especially R5, R5-20, R20 including reversibility by bronchodilator. Results: Averages of R5-20 in GroupBA/Group CVA/Group AR are 0.80/0.51/0.44, those of R5 are 3.68/2.95/2.70, those of R20 are 2.88/2.43/2.27. Values are significantly (p<0.01)higher in Group BA than in the other two groups, and the ratio of average values in Group BA to those in Group CVA of R5-20, R5, R20 are re-spectively 1.57, 1.25, 1.19. Therefore the ratio of R5-20 is the highest. And only average of R5 is significantly (p<0.05) higher in Group CVA than inGroup AR. Furthermore, reversibility of R5 is higher with prominent significance (p<0.001) in Group CVA than in Group AR, but reversibility of R5-20 is not significantly different among three groups. Conclusion: It was shown that in Group BA both R5 and R5-20 elevate, but in Group CVAonly R5 elevates. So the condition with wheeze may suggest the unequal ventilation, and in such cases, especially with high R5-20 value, we shouldchoose special care e.g. inhalation therapy in consideration of particle size. On the other hand, reversibility test with R5-20 is not so useful as withR5, so this might be a supporting evidence for the argument that R5-20 represents the frequency dependence of respiratory resistance, not pe-ripheral airway resistance.

110

PosterSession

PE2-10 “Recurrent episodes of prolonged cough” is a useful medical history to distinguish between Post-Infectious Cough (PIC) andCough Variant Asthma (CVA) for diagnosis

Masaaki Mikami (Hosshoji Internal Clinic, Japan)

Background:Many patients visit primary care clinics with a complain of cough. Among the different diagnosis for cough, PIC and CVA may bethe most popular of etiology. Methods:We retrospectively investigated in 160 patients with a complaint of cough to assess usefulness of medicalhistories for differential diagnosis between PIC and CVA. Result: PIC was diagnosed in 91 (57%) patients, CVA in 34 (21%), atopic cough in 12 (7%),chronic obstructive pulmonary disease in 9 (6%), sinobronchial syndrome in 6 (4%), and gastro-esophageal reflex disease in 4 (3%). 21% patients ofPIC and 91% patients of CVA had history of“recurrent episodes of prolonged cough”. For rule-in CVA for diagnosis, history of“recurrent epi-sodes of prolonged cough”showed to be 3.64 as positive likelihood rate. On the other hand, rule-in PIC for diagnosis, no history of“recurrent epi-sodes of prolonged cough”showed to be 8.62 as positive likelihood rate. Conclusions: History of“recurrent episodes of prolonged cough”is a use-ful medical history to distinguish between PIC and CVA.

PE2-11 Exercise-Induced Bronchoconstriction (EIB) confirmed by arm ergometry exercise with exhaled gas analyses in respiratory dis-eases

Etsuo Fujita1), Ryosuke Horitani2), Tatsuya Aoki2), Tadayuki Hashimoto2), Kahoru Miyata3), Tomomi Nakao3), Mito Hayashi4), Hironobu Hoshiya5),Katsuhiro Yamamoto5), Kyuya Gose6), Yuji Tohda6), Kousuke Shimada7) (Department of Respiratory Medicine, Hashimoto Municipal Hospital, Ja-pan1); Department of Internal Medicine, Hashimoto Municipal Hospital, Japan2); Department of Internal medicine of Endocrinology & Metabolism,Hashimoto Municipal Hospital, Wakayama, Japan3); Department of Orthopedics, Hashimoto Municipal Hospital, Japan4); Department of Cardiol-ogy, Hashimoto Municipal Hospital, Japan5); Department of Respiratory Medicine and Allergology, Kindai University School of Medicine, Japan6);Department of Surgery, Hashimoto Municipal Hospital, Japan7))

Purpose: In order to clarify the complications of exercise-induced asthma derived from exercise-induced bronchoconstriction (EIB), we evaluatedexercise tolerance by arm ergometry in patients who had related respiratory diseases and were not capable of performing walking exercise testssuch as treadmill tests.Methods: Arm ergometry exercise tests were performed in 25 patients (M 12, F 13; age 83.9±4.7 yrs (mean±SD); COPD,5; atypical mycobacteriosis, 5; pneumonia, 3; bronchial asthma, 3; bronchitis, 3; aspiration pneumonia, 2; bronchiectasis, 2; lung tumor, 1; and inter-stitial pneumonia, 1). We used Fitmate for exhaled gas analyses. EIB was evaluated by auscultation before and after exercise. Results: V’O2 peakwas 5.3±1.6 ml/kg/min, and anaerobic threshold (AT) was 4.6±1 ml/kg/min. Pulmonary function tests showed FEV1 levels of 1.09±0.50 L, FVClevels of 1.66±0.59 L, and FEV1% levels of 66.4±19.0%. FEV1 correlated significantly with V’O2 peak (r=0.582, P=0.0179). Based on auscultation re-sults, a few patients had suspected EIB after these exercise tests. Conclusion: These arm ergometry exercise tests with exhaled gas analyseswere helpful for identifying EIB even at the initiation of rehabilitation in respiratory diseases.

PE2-12 Ten-year trends in the prevalence of allergic diseases and their associated factors in young adults: analysis of the Hokkaido Uni-versity students

Munehiro Matsumoto1), Masaru Suzuki1), Michiko Sato1), Yuki Abe1), Akira Oguma1), Nozomu Takei1), Machiko Sasaki1), Hirokazu Kimura1),Kaoruko Shimizu1), Satoshi Hashino2), Satoshi Konno1) (Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine,Hokkaido University, Japan1); Hokkaido University Health Care Center, Japan2))

Background: The prevalence of allergic diseases has been increasing for decades worldwide, particularly in developed countries. However, fewstudies have focused on the more recent changes in the prevalence of these diseases in non-smoking young adults. Methods: The study includedfirst-year students of the Hokkaido University from 2011 to 2020. We conducted a questionnaire survey every year for a total of 23511subjects.Asthma was defined as an affirmative response to the question“Have you had wheezing or whistling in your chest at any time in the last 12months?”which is identical to those of the Japanese edition of the European Community Respiratory Health Survey (ECRHS) questionnaire. Thepresence of other allergic diseases was also asked in the questionnaire. Trends in the presence of allergic diseases were evaluated, based on thehometown area (Hokkaido and outside Hokkaido) separately, because of the very low prevalence of cedar allergy in the Hokkaido area. We alsoevaluated associations among disease conditions and those with body mass index (BMI), history of viral infections during childhood (measles, ru-bella, varicella, and mumps), vaccination history (measles, rubella), and pet ownership. Results: The prevalence of asthma did not change from2011 to 2020 in both areas (mean 5.9% in Hokkaido, mean 5.2% outside Hokkaido). The prevalence of seasonal allergic rhinitis remained to be highoutside Hokkaido with a significant trend of increase (36.7% in 2011, 53.2% in 2019). However, the prevalence of seasonal allergic rhinitis in Hok-kaido showed only a slight increase during the same period (16.6% in 2011, 21.0% in 2019). As expected, the higher BMI was significantly associ-ated with the prevalence of asthma in both areas (p<0.05), whereas food allergy was negatively correlated with BMI (p<0.05). Conclusion: Overthe course of the decade, the prevalence of asthma remained unchanged among young adults, though the prevalence of seasonal allergic rhinitistended to increase, with a tendency to vary by place of origin. Although there was a positive correlation between asthma and food allergy, theywere inversely correlated with each other with respect to BMI.

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PosterSession

PE2-13 Clinical characteristics of patients with not well-controlled severe asthma

Takae Tanosaki1,2), Hiroki Kabata1,2), Masako Matsusaka3), Jun Miyata4), Katsunori Masaki1,2), Takao Mochimaru5), Shinichi Okuzumi1,2),Misato Kuwae1,2), Risa Watanabe5), Yuto Akiyama1,2), Keeya Sunata1,2), Miyuki Nishie1,2), Yusuke Suzuki6), Koichi Sayama7), Kenji Izuhara8),Koichiro Asano9), Koichi Fukunaga1,2) (Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Japan1); KeioAllergy Center, Keio University Hospital, Japan2); Department of Laboratory of Bioregulatory Medicine, Kitasato University School of Pharmacy,Japan3); Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Japan4);Respiratory Medicine, National Hospital Organization Tokyo Medical Center, Japan5); Respiratory Medicine, Kitasato University Kitasato Insti-tute Hospital, Japan6); Respiratory Medicine, Kawasaki Municipal Hospital, Japan7); Division of Medical Biochemistry, Department of BiomolecularSciences, Saga Medical School, Japan8); Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Japan9))

Background: Among patients with severe asthma in Japan, clinical phenotypes of uncontrolled patients remain unclear.Methods: Japanese adultpatients with severe asthma were enrolled at Keio University Hospital and its affiliated hospitals in this observational study (Keio Severe AsthmaResearch Program). We evaluated clinical characteristics of patients with well-controlled and not well-controlled severe asthma under GINA step4 or 5 treatment. Results: A total of 154 patients (Age, 60.1±14.9 years; Men, 46.8%) were included in this study, and 87 patients (56.5%) had notwell-controlled (partly controlled and uncontrolled) asthma (GINA step 4, 42 patients; step 5, 45 patients). Overall, there were no significant differ-ences in clinical characteristics between patients with well-controlled and not well-controlled asthma. However, cluster analysis revealed distinct5 clusters (Cluster 1, well-controlled; Cluster 2, eosinophilic; Cluster 3, nontype 2 inflammation; Cluster 4, high periostin; and Cluster 5, late-onsettype 2 inflammation). Among clusters 2 - 5, which were not well-controlled, cluster 3 was characterized by low eosinophil counts, low periostin lev-els, and less frequent olfactory disturbance. Cluster 3 had the worst asthma control. Conclusions: Patients with severe asthma were divided intowell-controlled and not-well controlled asthma, and we confirmed heterogeneity of not well-controlled severe asthma. These patients, especiallynon-type 2 phenotype, require a further therapeutic approach.

PE2-14 Correlations of forced oscillometric bronchodilator response with airway inflammation and disease duration in asthma

Naoko Higaki1), Hiroshi Iwamoto1), Kakuhiro Yamaguchi1), Shinjiro Sakamoto1), Yasushi Horimasu1), Takeshi Masuda1), Shintaro Miyamoto1),Taku Nakashima1), Shinichiro Ohshimo2), Kazunori Fujitaka1), Hironobu Hamada3), Noboru Hattori1) (Department of Molecular and Internal Medi-cine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan1); Department of Emergency and Critical Care Medicine,Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan2); Department of Physical Analysis and Therapeutic Sciences,Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan3))

Background: Airway resistance and reactance, measured by forced oscillometry, are used to measure airway obstruction in patients withasthma. This study aimed to investigate oscillometric bronchodilator responses in treated and untreated asthma and evaluate its association withairway inflammation and disease duration. Methods: This study included 30 non-smoking patients with mild to moderate treated asthma, 25 pa-tients with newly diagnosed untreated asthma, and 29 control subjects. Spirometric and oscillometric measurements were performed before andafter inhalation of 400 g salbutamol. Disease duration was defined as the number of years since asthma diagnosis. Results: At airway resistance of5 Hz (R5) and 20 Hz (R20), bronchodilator responses in patients with untreated and treated asthma were greater than those in control subjects. Inpatients with untreated asthma, higher fractional exhaled nitric oxide concentration (FeNO) levels were strongly correlated with greater reversi-bility of R20 (rs=-0.620, p<0.001). In patients with treated asthma, there was no significant association between FeNO and oscillometric reversibil-ity, whereas longer disease duration was significantly associated with lesser bronchodilator response at R20 (rs=0.430, p<0.05). Treated asthmapatients with longer disease duration (≧10 years) showed significantly higher post-bronchodilator R5 and R20 than treated asthma patients withshorter disease duration (<10 years). Conclusion: The present study provides further evidence of an association between airway inflammationand variable airway obstruction in asthma patients and indicates that long-term disease duration could be related to poorly reversible airway re-sistance in patients with mild to moderate asthma.

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PosterSession

Poster Session 3Adult asthma 2

PE3-1 IL-13/15-lipoxygenase-1 axis drives intracellular glutathione oxidation in asthmatic airway epithelial cells

Tadao Nagasaki1,2), Jinming Zhao2), Yanhan Deng2), John B Trudeau2), Yoshinori Minami2), Sally E Wenzel2) (Department of Respiratory Medicine,Osaka Saiseikai Nakatsu Hospital, Japan1); Department of Environmental and Occupational Health, University of Pittsburgh Graduate School ofPublic Health, USA2))

Background: While extracellular reduced glutathione (GSH)/oxidized glutathione (GSSG) redox balance has been reported to be altered in asthma,nothing is known regarding of intracellular GSH/GSSG redox state. Importantly, intracellular GSH, a major intracellular antioxidant, plays an essentialrole preventing ferroptotic cell death by limiting accumulation of hydroperoxy-phospholipids generated by 15-lipoxygenase-1 (15LO1), through promo-tion of glutathione peroxidase-4 (GPX4) activity. Our hypothesis is that the intracellular GSH/GSSG redox balance in asthma is more oxidized in asthma,due to changes in both GSH availability and its metabolism. To address this hypothesis, we measured 1) intracellular GSH/GSSG, the cystine and glu-tamine transporters (solute carrier family 7 member 11 (SLC7A11)) and 15LO1 in freshly brushed asthmatic and healthy control (HC) human bronchialepithelial cells (HBEC) and determined 2) the impact of IL-13 on intracellular GSH to GSSG ratios, SLC7A11, 15LO1, and GPX4 and 3) whether 15LO1 ac-tivity contributed to lower GSH/GSSG. Methods: Epithelial brushings were bronchoscopically obtained from 4 mild/moderate asthma (MMA), 11 se-vere asthma (SA), and 11 HC subjects. Intracellular GSH, GSSG (enzymatic method), 15LO1 and SLC7A11 protein (Western blot) were measured inbrushed and air-liquid interface cultured HBEC. HBEC were treated with a 15LO1 inhibitor or knockdown. Results: Ex vivo fresh both MMA and SAhad lower intracellular GSH/GSSG than HC (p＝0.004 and p<0.0001 respectively). This intracellular GSH/GSSG significantly correlated with exhaled NO(r＝-0.40, p＝0.04), FEV1 (r＝0.42, p＝0.03), and 15LO1 (r＝-0.62, p＝0.01). IL-13 decreased GSH/GSSG (p＝0.03) despite increases in SLC7A11 protein. IL-13 concurrently increased 15LO1 and GPX4 protein. Inhibition or knockdown of 15LO1 restored GSH/GSSG in IL-13 treated cells to control levels (p＝0.008, 0.02, respectively). Conclusion: Our results suggest that asthmatic epithelial cells are in an oxidized state with low intracellular GSH/GSSG associ-ated with worsened inflammation and disease. IL-13 drives this primarily through high consumption of GPX4 in response to an active 15LO1.

PE3-2 The single nucleotide polymorphism (SNP) rs1799971 in the µ-opioid receptor gene (OPRM1 ) is a novel risk factor for asthmaexacerbation

Kaori Kawakami1), Tomomitsu Miyasaka1), Yutaka Nakamura2), Satoshi Miyata3), Miki Sato1), Ichiro Sora4), Hirohito Metoki5), Kohei Yamauchi6),Julie A Blendy7), Tasuku Kawano1), Hiroaki Shimokawa3,8), Tomoko Takahashi1), Motoaki Takayanagi1), Isao Ohno2) (Division of Pathophysiology,Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan1); Center for Medical Education, Faculty of Medicine,Tohoku Medical and Pharmaceutical University, Japan2); Department of Evidence-Based Cardiovascular Medicine, Tohoku University GraduateSchool of Medicine, Japan3); Department of Psychiatry, Kobe University Graduate School of Medicine, Japan4); Division of Public Health, Hygieneand Epidemiology Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Japan5); Division of Respirology, Department of InternalMedicine, Takizawa Central Hospital, Japan6); Department of Pharmacology, University of Pennsylvania Medical School, USA7); Department ofCardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan8))

Objective: The mu-opioid receptor (MOPR) is predominantly responsible for stress-induced asthma exacerbation. In the present study, we evalu-ated the effect of functional single nucleotide polymorphism (A118G SNP, rs1799971) located in the human MOPR gene, OPRM1 , on asthma exac-erbation.Methods:We initially assessed the severity in outpatients with asthma carrying this SNP. Furthermore, using an ovalbumin-induced ex-perimental asthma model, we investigated differences in immune response relevant to asthma exacerbation between WT and Oprm1 G112 miceharboring functionally equivalent SNP to OPRM1 G118. Results: OPRM1 A118G SNP was analyzed in 292 outpatients with asthma, and 36%,41%, and 23% of them carried the AA, AG, and GG genotypes, respectively. Airway hyperresponsiveness (AHR) to methacholine was analyzed in168 patients. Compared with patients carrying the A allele, patients with the GG genotype exhibited significantly enhanced AHR. In an analysis ofthe asthma mouse model, compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features. Correlated with the in-creased number of eosinophils in bronchoalveolar lavage (BAL) fluids of GG mice, greater amounts of Ccl11 mRNA and IL-4+ CD4+ effector mem-ory T cells were observed in the lungs of GG mice. Furthermore, the greater number of eosinophils in BAL fluids of GG mice was eliminated whenwe administrated fingolimod or naloxone methiodide. Conclusions: These data suggest that OPRM1 A118G SNP is associated with enhancedadaptive type 2 immune responses in peripheral lymphoid organs, which may contribute to asthma exacerbation in asthmatics who carry theOPRM1 GG genotype.

PE3-3 Cadherin related family member 3 activates the effector functions of neutrophils

Toshiaki Shimizu1,2), Kazuyuki Nakagome1), Yury A Bochkov3), Yutaka Ueda1), Takehito Kobayashi1), Tomoyuki Soma1), Hiroaki Harada2),Keishi Fujio2), James E Gern3,4), Makoto Nagata1) (Department of Respiratory Medicine and Allergy Center, Saitama Medical University, Japan1);Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Japan2); Department of Pediatrics, School of Medi-cine and Public Health, University of Wisconsin, USA3); Department of Medicine, School of Medicine and Public Health, University of Wisconsin,USA4))

Background: Cadherin related family member 3 (CDHR3) is expressed on the ciliated airway epithelium cells. It works as a receptor for rhinovi-rus C, which is one of the main causes of asthma exacerbation. Single nucleotide polymorphism of the gene is known to be related with the sever-ity of pediatric asthma. However, little is known about its functions. We examined the possible effects of CDHR3 on neutrophil functions by in vi-tro experiments. Methods: We collected peripheral bloods from healthy human donors and isolated neutrophils by density gradient centrifuga-tion. Neutrophils were incubated with CDHR3 and their adhesion was measured using residual peroxidase assays or by fluorescently labeled neu-trophils. Superoxide anion (O2-) generation was measured as superoxide dismutase-inhibitable reduction of cytochrome C. Results: CDHR3 in-duced neutrophil adhesion as compared to that without CDHR3. Furthermore, CDHR3 induced neutrophil O2- generation. Conclusion: Thesefindings suggested that CDHR3 activated the effector functions of neutrophils in vitro. As neutrophils play roles during the viral infection, theseeffects may contribute to the development of asthma exacerbation.

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PosterSession

PE3-4 T-cell death-associated gene 8 is a new biomarker for the severity and the exacerbation in bronchial asthma

Hiroaki Tsurumaki1), Haruka Aoki-Saito1), Yasuhiko Koga1), Makiko Sato1), Masakiyo Yatomi1), Asuka Jingu1), Kenichiro Hara1), Noriaki Sunaga1),Seishi Yoshimi2), Toshitaka Maeno1), Takeshi Hisada3) (Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Ja-pan1); Tone Central Hospital, Japan2); Gunma University, Faculty of Medicine School of Health Sciences, Japan3))

Background: The pH of the bronchoalveolar space has been shown to fall in the presence of inflammatory diseases like bronchial asthma (BA). T-cell death-associated gene 8 (TDAG8) has been known as a proton-sensing G-protein-coupled receptor that is mainly expressed in hematopoieticcells like neutrophils, eosinophils, and macrophages; its expression is elevated in the activated bronchial epithelial cells. We have previously re-ported that TDAG8 is a negative regulator for neutrophilic inflammation in the lipopolysaccharide-induced lung injury model and regulates Mu-cin 5AC (MUC5AC) in the ovalbumin-induced asthma model. The role of TDAG8 has been reported in cells and mice, however, its clinical role inBA remains unknown. Accordingly, we explored the clinical role of TDAG8 in BA. Methods: Patients with BA who visited the Department ofRespiratory Medicine, Gunma University Hospital and Tone Central Hospital from July 2017 to July 2019 were included in the study. Informedconsent was obtained from all participants. Total RNA in blood of patients was isolated, and reverse-transcribed. The expression of mRNAs wasmeasured by quantitative real-time PCR. The relationship between TDAG8 mRNA and clinical findings, including symptom scores, laboratoryfindings, and frequency of exacerbation, were examined. All procedures performed in this study involving human participants were in accor-dance with Gunma University Hospital clinical research review board requirements, and the declaration of Helsinki and its later amendments. Re-sults: Median age of subjects, and percentage of males were 69.5 years and 45.7% respectively. The rates of treatment steps 2, 3, 4 and 5 in theGlobal Initiative for Asthma (GINA) guidelines, were 6.5%, 39.1%, 21.7% and 32.6% respectively. TDGA8 mRNA was negatively correlated to thescores of the asthma control test. TDAG8 mRNA in the patient group with exacerbations was lower than those without exacerbations. Conclu-sion: TDAG8 could be a new biomarker for severity and exacerbation in BA.

PE3-5 TRPA1 channel mediates cold air-induced aggravation of airway inflammation

Takahiro Matsuyama, Kentaro Machida, Yoichi Doutake, Koichi Takagi, Hiromasa Inoue (Department of Pulmonary Medicine, Graduate School ofMedical and Dental Sciences, Kagoshima University, Japan)

Background: Ambient temperature change, especially cold air exposure, is considered to trigger asthma exacerbation, but the exact mechanismhas not been clarified. The aim of this study is to address the underlying mechanism of cold air-provoked asthma exacerbation. In this study, weexamined whether cold air exposure contributed to the aggravation of airway inflammation, focusing on the functional role of Transient receptorpotential A1 (TRPA1) channel, a subclass of TRP channels and a sensor that response to cold temperature, by using a papain-induced airway in-flammation model. Methods:Wild-type (WT) and TRPA1-deficient (TRPA1-/- ) mice were treated with papain intranasally for three consecutivedays under different temperature conditions, room temperature (RT) or temperature variation (TV) between room temperature and cold air ex-posure. RT was set at 22 C. In TV group, the temperature was set at 22 C for 12 h and 4 C for 12 h. 24 hours after last administration, bronchoal-veolar lavage fluid (BALF) and lung tissues were collected to analyze the airway inflammation. Results: Intranasal administration of papain re-sulted in an increased the number of eosinophils in BALF. The number of eosinophils in BALF of TRPA1-/- mice was comparable with that ofWT mice in RT group. In WT mice, the number of eosinophils in BALF was further increased in TV group compared to RT group. On the otherhand, in TRPA1-/- mice, the increase number of eosinophils induced by cold air exposure was suppressed. The concentration of IL-5 and IL-13and the number of ILC2s in BALF were also reduced in TRPA1-/- mice with cold air exposure. Conclusion: In WT mice, cold air exposure aggra-vated the eosinophilic airway inflammation through Type 2 cytokine production in a papain-induced airway inflammation model. TRPA1-/- miceattenuated the aggravation of eosinophilic airway inflammation and reduced the Type 2 cytokine production induced by cold air exposure. Thesefindings suggested that TRPA1 channel might have an essential role in regulating cold air-induced aggravation of airway inflammation.

PE3-6 Cooperative effect of type 2 inflammatory mediators on pulmonary function in patients with severe asthma

Yuki Hoshino, Tomoyuki Soma, Yoshitaka Uchida, Sachiko Miyauchi, Hidetoshi Iemura, Erika Naito, Kazuki Katayama, Ryu Sekiya,Kazuyuki Nakagome, Makoto Nagata (Department of Respiratory Medicine, Saitama Medical University, Japan; Allergy Center, Saitama MedicalUniversity, Japan)

Rationale: There is evidence that some eicosanoids play roles as inflammatory mediators in airway of asthma. Associations among concentra-tions of eicosanoids, type 2 cytokines and pulmonary function in asthma have not fully established.Methods: This study was a sub-analysis of datafrom our previous study published on the Annals of Allergy Asthma and Immunology in 2019 (Uchida Y, et al.). We determined differences of con-centrations of eicosanoids in sputum and type 2-related cytokines between non-severe (n=17) and severe asthmatics (n=20) based on ATS/ERSdefinition. We also evaluated relationship between concentrations of those mediators and pulmonary function in asthmatics. In sputum, Cysteinylleukotrienes (CysLTs) and prostaglandin D2-MOX (PGD2-MOX) by EIA, and IL-5 and IL-13 by ELISA were measured. Results: There was no dif-ferences in concentrations of sputum eicosanoids and IL-5 between non-severe and severe asthmatics. Sputum IL-13 were not detected. SputumCysLTs concentrations were significantly correlated with sputum PGD2-MOX and IL-5 in the severe (r=0.74, P=0.001; r=0.66, P=0.037, respec-tively), but not in the non-severe asthmatis. Concentrations of sputum CysLTs, PGD2-MOX and IL-5 were negatively correlated with FEV1 (r=-0.85, P<0.001; r=-0.47, P=0.05; r=-0.69, P=0.013, respectively) in severe asthmatics. Percentages of sputum eosinophil were negatively correlatedwith FVC (r=-0.58, P=0.008). Conclusions: Some eicosanoids and type 2 cytokines might cooperatively deteriorate pulmonary function in severeasthmatics despite of treatment according to guideline.

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PosterSession

PE3-7 Cytokine profile in patients with asthma attack

Luna Okubo1), Naoya Takeda2), Yoshihiro Suzuki2), Kuniya Nakashima2), Motoyo Asano2), Fumika Koike1), Akane Ide1), Miho Akaza1),Yasunari Miyazaki3), Yuki Sumi1) (Department of Respiratory and Nervous System Science, Tokyo Medical and Dental University, Japan1); De-partment of Respiratory Medicine and Allergy, Kariya Toyota General Hospital, Japan2); Department of Respiratory Medicine, Tokyo Medical andDental Univercity, Japan3))

Background: Studies on the pathogenesis of asthma exacerbation were few and the mechanism for asthma attack remains obscure. Objective:The purpose of this study is to clarify the characteristic cytokine profiles of asthma exacerbation. Methods: Serum cytokine levels were meas-ured in patients visiting hospital for asthma attack, and compared with cytokine levels in patients with asthma during stable period and in normalsubjects. Serum IL-4, IL-5, IL-10, IL-13, IL-17A, IL-17F, IL-33, and TSLP concentration were measured by the ELISA method or Multi-Analyte in16 patients with asthma attack, in 49 patients with asthma during stable period, and 20 normal subjects. Result:We found that serum IL-10 andIL-13 levels were significantly increased during asthma attack compared to stable period. There were no significant differences in serum IL-17A,IL-17F, IL-33, and TSLP levels between in asthma attacks and in stable asthmatics patients. On the other hand, serum levels of IL-4 and IL-5 inasthmatics tended to decrease, although not significantly different. Discussion: IL-10, known as inhibitory cytokine, was increased to suppress ex-cessive inflammation during asthmatic attacks, leading to decreased levels of IL-4 and IL-5. However, IL-13 level was increased by unknownmechanisms, such as by the secretion of certain cells. IL-13 induces mucus secretion, airway wall thickening, and bronchoconstriction and couldcause asthmatic attack. These results suggested that asthma attacks were triggered when the usually well-regulated suppression of IL-13 pro-duction was disrupted. Our data supports previous studies that high fractional exhaled nitric oxide (FeNO), which are produced by IL-13, levelswere associated with greater risk of asthma exacerbations. Conclusion: It has been suggested that increased IL-13 leads to asthma attacks.

PE3-8 Changes of the levels of eosinophil-derived protein in sputum with response to benralizumab in patients with severe asthma

Toshiyuki Koya1), Akira Saito1), Natsumi Sakai1), Mio Toyama1), Keisuke Tsukioka1), Yosuke Kimura1), Masachika Hayashi1), Takashi Hasegawa2),Toshiaki Kikuchi1) (Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sci-ences, Japan1); Department of General Medicine, Niigata University Medical and Dental Hospital, Japan2))

Rationale: The anti-interleukin-5 receptor α chain monoclonal antibody, benralizumab, is used to treat severe asthma and has the potential toeliminate eosinophils even in the airway. However, the effect of benralizumab in reducing the levels of eosinophil related proteins in the airwayhas not been fully elucidated. We investigated the changes of eosinophilic cationic protein (ECP) and Charcot-Leyden crystal (CLC) protein in spu-tum in accordance with clinical efficacy.Materials and Methods:We used the Asthma Control Test to assess the clinical efficacy of benralizumabin treating 10 patients with severe asthma. We also investigated blood and sputum eosinophil, fraction of exhaled nitric oxide, pulmonary function,and the frequency of exacerbation. We also measured the levels of ECP and CLC protein in sputum supernates. Results: Among 10 patientstreated with benralizumab, seven patients effectively responded to the treatment in terms of asthma symptoms. The number of blood eosinophilas well as the percentage of sputum eosinophil in all patients became almost zero, and ECP and CLC protein in sputum supernates were de-creased in most patients. Conclusion: These data suggest benralizumab, anti-IL-5 receptor a chain antibody has a great potency to erase not onlyeosinophils but also eosinophilic cytoplasmic protein even in the airway.

PE3-9 Global Asthma Network (GAN): factors associated with asthma in parents/caregivers of adolescents living in Uruguaiana, Brazil

Marilyn Urrutia-Pereira1), Herberto Chong Neto2), Pietro Nunes Rinelli1), Laura Simon1), Philippa Ellwood3), Luis García-Marcos4), Dirceu Solé5) (Fed-eral University of Pampa, Brazil1); Federal University of Paraná, Brazil2); University of Auckland, New Zealand3); University of Murcia, Spain4);Federal University of São Paulo, Brazil5))

Rationale: The GAN Study simultaneously assessed the frequency of asthma and associated factors in adolescents and their parents. GAN’s ob-jectives are demonstrating new evidence to better understand asthma, its management practices of key risk factors, and the urgent need to re-duce its global burden.Methods: Cross-sectional comparative study of Phase 1 of GAN, conducted in Uruguaiana, BR. Eight hundred and ninety-six parents or caregivers of participating adolescents, mean age 43 years, 17.6% male, answered the standard questionnaire. In addition to theprevalence of asthma symptoms, factors associated with asthma expression in these individuals were identified by logistic regression. Results:Among those responsible for adolescents, wheezing in the last 12 months occurred in 18.4%, had 4-12 wheezing episodes 17.6%, woke up 1 or morenights with wheezing, 26% and 18.2% lack of air during sleep, 12.7% asthma, but only 7.3% have any action plan. The age of the first wheezing was14 years, 12% had asthma attacks in the last 12 months and 11.5% used bronchodilators, but only 2.4% used inhaled corticosteroids. The followingwere identified as associated with wheezing: work causing wheezing (OR: 10.0; 95% CI: 5.7-18.52; p<0.05); have a diagnosis of asthma ever (OR: 5.1;95% CI: 3.1-8.3); p<0.05), have allergic rhinitis (OR: 2.2; 95% CI: 1.5-3, 4; p<0.05), mold exposure (OR: 1.8; 95% CI: 95% CI: 1.1-3.0; p<0.05); few ciga-rettes (OR: 1.03; 95% CI: 1.0-1.08), p<0.05), use of liquefied petroleum gas for cooking (OR: 0.68; 95% CI: 0.4-1.04; p>0.05) and consume raw vegetables(OR: 0.80; 95% CI: 0, 7-0.9; p<0.05). Conclusions: Asthmatic parents of adolescents participating in GAN do not have their disease controlled, usemore rescue medication than control medication. Some associate work with wheezing attacks as well as having other allergic diseases. Consump-tion of a diet rich in vegetables was identified as protective. Keywords: risk factors, parents, Global Asthma Network

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PosterSession

PE3-10 The ralationship between high blood eosinophil count in asthma and metabolic condistions

Asami Minamibata1,2), Taichiro Arimoto1,2), Yoshinori Marunaka2) (Department of Respiratory Medicine, Clinic, Kyoto Industrial Health Associa-tion, Japan1); Research Center for Clinical Respiratory Physiology, Research Institute for Clinical Physiology, Kyoto Industrial Health Association,Japan2))

Background: Asthma consists of heterogenous conditions. Some findings indicate high blood eosinophil count in asthma would reflect metabolicconditions, however those findings are still contradictory. Therefore, we tried to confirm how metabolic conditions are reflected by the bloodeosinophil in asthma. Methods: 717 asthma patients taking a medical check-up between April, 2017 and March, 2018 were divided into threegroups based on the levels of blood eosinophil: high, > top 25th percentile (first quartile); low, < bottom 25th percentile (third quartile); median, be-tween top 25th percentile(first quartile) and bottom 25th percentile (third quartile). We clarified how metabolic conditions were reflected by theblood eosinophil in asthma, comparing metabolic conditions (hypertension, dyslipidemia, diabetes mellitus, hyperuricemia and fatty liver) in highgroup with those in low group. Results: As compered with low eosinophil group, patients in high eosinophil group were in severe metabolic condi-tions. In female, BMI was higher eosinophil group than low eosinophil group, while these two groups in male showed no significant difference inBMI. In logistic regression models adjusting for BMI, age, sex, smoke and alcohol, high eosinophil group had higher prevalence of hypertension(odds ratio (OR) 2.32, 95% confidence interval (CI) 1.22-4.42), hyperuricemia (OR 2.08, 95% CI 1.17-3.71) and fatty liver (OR 1.92, 95% CI 1.10-3.36). Onthe other hand, there was no significant difference in dyslipidemia or diabetes mellitus between high and low eosinophil groups. Conclusion:Asthma patients with high blood eosinophil show much severer hypertension, hyperuricemia and fatty liver than those with low blood eosinophil.Within our knowledge, this is the first report clearly concluding the relationship between eosinophil and three metabolic conditions (hypertension,hyperuricemia and fatty liver), although further studies are required to clarify how eosinophils with a high level in blood would cause hyperten-sion, hyperuricemia and fatty liver.

PE3-11 Gender-specific impact of obesity on type 2 inflammation in adults with asthma

Michiyoshi Imaoka (Department of Medicine, Matsuyama Kinen Hospital, Japan)

Background: Although recently the obese female asthma has been described as a distinct pheno-endotype of severe asthma, the underlyingpathogenetic mechanisms for the interaction between obesity and asthma and the role of female sex are unclear. We examined the gender-specific impact of obesity on type 2 inflammation in steroid-nave adults with asthma. Methods: The subjects comprised 471 Japanese adults [180men and 291 women, median (range) age 57 (20-92) years] with asthma who were untreated with glucocorticosteroids and during attack-free peri-ods. We used peripheral blood eosinophil counts (PBECs) and the levels of fractional exhaled nitric oxide (FeNO) as markers of type 2 inflamma-tion. We retrospectively compared these two biomarkers between obese [(BMI) (the weight in kilograms divided by the square of the height inmeters), ≧25] and normal weight patients (BMI, 18.5 to 24.9), separately for men and women; We also retrospectively compared these twobiomarkers between men and women, separately for obese and normal weight patients. Results: In 180 men, there was no significant difference inboth PBECs and FeNO levels between 76 obese and 104 normal weight patients (275±286 and 300±518/µL, respectively; P＝0.68) (54.1±54.2 and48.6±61.6 ppb, respectively; P＝0.53); in 291 women, 77 obese patients had significantly lower PBECs than 214 normal weight patients (198±144versus 253±289/µL, respectively; P＝0.03), and had lower, but not statistically significant, FeNO levels compared with 214 normal weight pa-tients (34.1±32.4 versus 41.2±44.6 ppb, respectively; P＝0.14). In 153 obese patients, 77 women had significantly lower PBECs and lower FeNOlevels than 76 men (198±144 versus 275±286/µL, respectively; P＝0.04) (34.1±32.4 versus 54.1±54.2 ppb, respectively; P＝0.007); in 318 normalweight patients, there was no significant difference in both PBECs and FeNO levels between 104 men and 214 women (300±518 and 253±289/µL, respectively; P＝0.39) (48.6±61.6 and 41.2±44.6 ppb, respectively; P＝0.28). Conclusions: Our results show that obesity reduce type 2 inflam-mation in women, but not in men with asthma. Other inflammatory types than type 2 inflammation alone may play a major role in the pathogene-sis of the obese female asthma.

PE3-12 Effect of fungal sensitization on the relationship between total serum IgE and type 2 inflammation in adults with allergic asthma

Michiyoshi Imaoka (Department of Internal Medicine, Matsuyama Kinen Hospital, Japan)

Background: Although asthmatic patients sensitized to fungi are reported to have more severe asthma, the underlying immunopathogenicmechanisms responsible for this severity have not been fully elucidated. We examined the effect of fungal sensitization on the relationship be-tween total serum IgE and type 2 inflammation in steroid-nave adults with allergic asthma. Methods: The subjects comprised 240 steroid-naveJapanese adults with allergic asthma [105 men and 135 women, median (range) age 52 (20-92) years] classified into 2 groups according to fungalsensitization: (1) Patients with fungal IgE sensitization; (2) Patients without fungal IgE sensitization. We used peripheral blood eosinophil countsand the levels of fractional exhaled nitric oxide (FeNO) during attack-free periods as markers of type 2 inflammation. We retrospectively analyzedthe correlation of total serum IgE levels with these two biomarkers, separately for each group. Results: In 60 patients sensitized to fungi, both pe-ripheral blood eosinophil counts and FeNO levels were not correlated with total serum IgE levels (r＝－0.15, P＝0.26) (r＝0.006, P＝0.97); in 180patients without fungal sensitization, both peripheral blood eosinophil counts and FeNO levels were correlated with total serum IgE levels (r＝0.48, P<0.001) (r＝0.39, P<0.001). Conclusions: Our results show that there is no significant correlation between total serum IgE and type 2 inflam-mation in adult allergic asthma with fungal sensitization; in adult allergic asthma without fungal sensitization, type 2 inflammation is correlatedwith total serum IgE. IgE may not be involved in major immunopathogenic pathways contributing to the severity of fungal asthma.

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PosterSession

Poster Session 4Air pollution and environmental allergens

PE4-3 Serological analysis for IgE against the booklice liposcelis bostrychophila , a common indoor insect pest, using recombinant al-lergen components

Osamu Ishibashi1), Masaya Sakaguchi1), Yuma Fukutomi2), Yuji Kawakami3), Takashi Inui1) (Graduate School of Life & Environmental Sciences,Osaka Prefecture University, Japan1); Clinical Research Center for Allergy & Rheumatologty, Sagamihara National Hospital, Japan2); Laboratoryof Environmental Science, FCG Research Institute Incorporation, Japan3))

Purpose: Booklice, belonging to the order Psocoptera, are common household insect pests that are distributed worldwide. Our serological studies demon-strated that specific IgE antibodies against Liposcelis bostrychophila (L. bostrychophila ), a common home-inhabiting species of booklice, were detected in serafrom 22% of allergic asthma patients, suggesting that booklice could be a potent inducer of respiratory allergy. We also identified a booklouse-specific protein,designated Lip b 1, as an allergen component of L. bostrychophila . Further, we have recently identified another candidate of L. bostrychophila allergen com-ponent, which is tentatively designated Per a 3-like protein (Per a 3-LP) as it shares 43% amino-acid homology with the american cockroach allergen compo-nent Per a 3. This study was conducted to evaluate IgE reactivity to recombinant Lip b 1 and Per a 3-LP proteins in sera from booklouse-sensitized asthma pa-tients.Methods: Maltose binding protein-fused Lip b 1 (MBP-Lip b 1) and histidine tag-fused Per a 3-LP (Per a 3-LP-His) were generated using an Escherichiacoli expression system and subjected to IgE-ELISA. The levels of specific IgE antibodies against these proteins in sera from booklouse-sensitized allergicasthma patients were evaluated by IgE-ELISA and western blotting. Results: IgE-ELISA revealed that sera from 56% and 22% of the booklouse-sensitized pa-tients showed dominant IgE reactivity to MBP-Lip b 1 and Per a 3-LP-His, respectively, compared to the non-allergic subjects’ sera. However, IgE reactivitylevels to MBP-Lip b 1 and those to Per a 3-LP-His are poorly correlated, indicating that allergen components that cause sensitization to booklice are differentdepending on the patients. Further, IgE-ELISA and western blotting under a denaturing condition revealed the different patterns of IgE reactivity to theseproteins, suggesting that the structural conformations of these proteins are crucial for their binding to IgE antibodies. Conclusion: Our data suggest that bothLip b 1 and Per a 3-LP are the allergen components of L. bostrychophila . Therefore, these proteins could serve as tools for the diagnosis of booklouse allergy.

PE4-4 Ultrafine particles change profilin-1 and cofilin-1 in human lung microvascular endothelial cells

An-Soo Jang, Pureun-Haneul Lee, Yun-Ki Lee (Department of Internal Medicine, Soonchunhyang University Hospital, Republic of Korea)

Background: Air pollutants exacerbates chronic airway disease such as asthma and COPD. But underlying mechanism for airway diseases re-mains unresolved. Objective: The aim of study was to identify protein expression in human lung microvascular endothelial cells (HMVEC-L) ex-posed to TiO2 ultrafine particles (UPs).Methods: A proteomic approach using 2DE and matrix assisted laser desorption time-of-flight spectrome-try (MALDI-TOF/TOF MS) on the peptide sequence was used to determine the different expression of proteins at 8hr and 24hr after treatmentof TiO2 UPs 20 µM and 40 µM to HLMVEC-L. Results: Treatment of HMVEC-L with TiO2 UPs 20 µM altered 10 protein spots. These proteins in-cluded calcium regulation, transport, cytoskeleton, and muscle contraction. At concentration of 40 µM altered 5 protein spots. These proteins in-cluded cytoskeleton, myosin regulation, action modulating, and GDP and GTP regulation. For validation immunohistochemical staining and West-ern blotting was perfomed on lung tissues from UPs exposed mice. Profilin-1 and Cofilin-1 were expressed in endothelium, epithelium, and inflam-matory cells and decreased in lung tissues of UPs exposed mice compared with sham treated mice. Conclusion: These results indicate that someof proteins may be an important role for airway disease caused by TiO2 ultrafine particles exposure.

PE4-5 Effect of different architectural styles and ventilation systems on seasonal changes of mite allergen (Der 1) levels in houses

Hideharu Shirai1), Hiromichi Yamaguchi2), Yudai Kohara3), Makoto Yoshida3), Junko Ishihara4), Jumpei Uchiyama5), Masahiro Sakaguchi5) (Environ-mental Allergens Info and Care, Japan1); Yamaguchi Respiratory and Dermatology Clinic, Japan2); Ichijo Co. Ltd, Japan3); Laboratory of PublicHealth Nutrition, Azabu University, Japan4); Laboratory of Veterinary Microbiology I, Azabu University, Japan5))

Background: Research on the influence of different architectural styles and ventilation systems on mite allergen levels is crucial to decrease miteallergen exposures in houses. The purpose of this study was to examine the seasonal changes in mite allergen (Der 1) levels on the floors and mat-tresses of houses with different architectural styles and ventilation systems.Methods: Thirty-two families, without considering the families’ histo-ries of allergies, participated in this study. Written consent was obtained from all the families. All 32 families lived in Shizuoka prefecture, Japan.Dust samples were monthly collected from the floors of the living rooms and mattresses in the bedrooms from March 2019 to February 2020. Miteallergen Der 1 (Der f 1 and Der p 1) levels were measured using sandwich enzyme-linked immunosorbent assays. The air temperature and rela-tive humidity in each house were measured every 3 hours using hygrothermography (174H, Testo K.K., Yokohama, Japan). Statistical significancewas set as P<0.05. Results: Eleven families lived in detached houses with balanced ventilation (group A), 10 families lived in detached houses withexhaust-only ventilation (group B), and 11 families lived in concrete apartment buildings with exhaust-only ventilation (group C). Dust samplesfrom floors and mattresses in all groups showed significant seasonal changes in Der 1 levels. Der 1 levels peaked in the summer months. Group Ashowed significantly lower levels of Der 1 in mattress dust than other groups. All groups showed significant seasonal changes in mean monthlytemperature and relative humidity. Group A showed significantly lower mean monthly relative humidity than other groups. Conclusion: Differ-ent architectural styles and ventilation systems may have some influence on mite allergen levels and could possibly be modified to decrease miteallergen exposure in houses.

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PosterSession

PE4-6 Allergen sensitization pattern in a Japanese general adult population

Asako Kitahara1), Yoshiro Yamamoto2), Yuma Fukutomi3), Yoshiki Shiraishi1), Jun Tanaka1), Tsuyoshi Oguma1), Masami Taniguchi3),Tadashi Nagai4), Koichiro Asano1) (Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Japan1); Depart-ment of Mathematics, Tokai University, Japan2); Clinical Research Center, Sagamihara National Hospital, Japan3); Japanese Red Cross CentralBlood Institute, Japan4))

Background and Purpose: Prevalence of allergen-specific IgE in general population is an important information to predict and prevent futureepidemics of allergic diseases. We have tried to clarify the sensitization patterns to allergens in a general population of Japanese adults. Methods:Eight hundred serum samples stocked in the Japanese Red Cross, which was obtained in 2005 for blood donation from the residents in Tokyoaged 20-59 years, were randomly selected maintaining the same proportion for sex and age groups. IgE levels, total and specific for 23 allergens,were measured by ImmunoCAP method. First, exploratory factor analysis was performed to uncover the structure among allergen-specific IgEs.Second, a hierarchical cluster analysis using Ward’s method was performed with parameters including age, gender, total IgE values, and the sen-sitization pattern identified by factor analysis. Results: Exploratory factor analysis identified 6 groups of allergens, including 1) airborne fungi, 2)commensal microorganisms in the skin, 3) group 1 pollens (cedar, cypress), 4) group 2 pollens (alder, weeds), 5) insects, and 6) dust mites/animaldanders. Sensitization to commensal microorganisms in the skin was most strongly associated with the levels of total IgE in serum. Three clusterswere identified: A) non-atopic type (median IgE 32 IU/mL), B) pollen-dominant sensitization type (median IgE 104 IU/mL), C) pan-atopic type (me-dian IgE 627 IU/mL). The pan-atopic group could be further classified into fungal sensitization-positive and -negative subtypes. Conclusion: Aller-gen sensitization patterns in Japanese adults were clarified.

PE4-7 Profile of house dust and storage mite sensitization in the Lithuanian population

Gabija Biliute1), Asta Miskiniene2), Loreta Bagdonaite3), Jolita Norkuniene4), Violeta Kvedariene5,6) (Vilnius University, Faculty of Medicine, Lithu-ania1); UAB In novum, Lithuania2); Vilnius University, Faculty of Medicine, Institute of Biomedical Sciences, Lithuania3); Vilnius Gediminas Techni-cal University, Lithuania4); Clinic of Chest diseases, Immunology and Allergology, Institute of Clinical Medicine, Vilnius university, Lithuania5); Vil-nius University Hospital Santaros Klinikos, Lithuania6))

Background: To evaluate the sensitization profile of house dust mite (HDM) and storage mite allergens (SM) in the Lithuanian population. Meth-ods: Blood samples of 179 perennial allergic rhinitis and/or bronchial asthma patients were studied. Sensitization towards HDM and SM was ana-lyzed with Allergen explorer (ALEX) macroarray tests at the laboratory“Invitro diagnostics”, Vilnius, Lithuania. 82 subjects were tested withALEX1 and 97 with ALEX2 macroarrays. Sensitization to HDM and SM allergen extracts and components were analyzed. Results: 179 patientswith suspected allergies were investigated: 94 (52,51%) females and 85 (47,48%) males. The study group included 111 children under 18 years ofage, average age 6,5 years and 68 adults, average age 38 years. Sensitivity to mite allergens was found in 57 (31,84%) individuals: 29 (50,88%) fe-males and 28 (49,12%) males. 49 (85.94%) patients were polysensitized. Most patients were positive to Der f 2 (n=41; 71,93%), Der p 2 (n=40; 70,18%),Der p 23 (n=34; 59,65%). 29 (50,88%) patients were also positive to other HDM allergen components: Der p 7 (n=17; 29,82%), Der p 5 (n=15; 26,32%),Der p 10 (n=6; 10,53%). The majority of patients (n=35; 61,4%) had high levels of IgE antibodies toward HDM (>15 kUA/L). 33 (57,89%) patients al-lergic to storage mites were sensitized to: Gly d 2 (n=24; 42,11%), Aca s (n=11; 19,3%), Tyr p (n=9; 15,79%) and other allergens. Levels of sIgE inmost individuals, sensitized to storage mites do not exceed 5 kUA/L. Some patients sensitized to HDM showed sensitization to SM, however all pa-tients sensitized to SM were also sensitized to HDM. Conclusion: A significant number of patients were sensitized to HDM and SM with an evendistribution between genders. MA profile of most patients included sensitization to Der f 2, Der p 2 and Der p 23. However, sensitization to minorallergen components such as Der p 5, Der p 7, Der p 10 and storage mites is also important for correct confirmation of allergic etiology of the dis-ease, although sensitization to these allergens was low. It is important to note, that all patients sensitized to SM were also sensitized to HDM.

PE4-8 The search for polycyclic aromatic quinones with amplifying action in antigen response

Kentaro Misaki1), Hirohisa Takano2,3), Hiroaki Kanazawa1), Ken-ichiro Inoue1) (School of Nursing, University of Shizuoka, Japan1); Graduate School ofGlobal Environmental Studies, Kyoto University, Japan2); Department of Environmental Engineering, Graduate School of Engineering, Kyoto Uni-versity, Japan3))

Background: It has not yet been elucidated in detail what kind of airborne particles including diesel exhaust particles (DEP) and their adherentchemical constituents contribute to the exacerbating activity for allergic and inflammatory respiratory diseases. The exacerbating activity of 2polycyclic aromatic quinones (1,2-naphthoquinone (1,2-NphQ) and phenanthrenequinone (PhQ)) was reported for allergic response in respiratoryorgans in vivo by our group. In the present study, the amplifying action of representative organic constituents in atmospheric samples, polycyclicaromatic quinones in inflammatory cytokine (IL-8) generation induced by mite antigen was evaluated in vitro .Methods: Human adenocarcinoma-derived alveolar basal epithelial cells (A549) were cultured in DMEM medium with 1% penicillin, and 1% streptomycin in 24 well collagen-coatedmicroplate (1.5×105 cells/well) over 1.5 day, then they were exposed for 48 h simultaneously to mite antigen (Dermatophagoldes farinae (Df) bodyextract) (10 µg/mL) and each quinone compound at the concentration less than those with cytotoxicity (n=3). Thereafter, generated IL-8 proteinlevels were measured with ELISA assay. Cytotoxicity was confirmed with cell viability in MTS assay. The amplifying action in IL-8 protein gen-eration was examined for 12 polycyclic aromatic quinones. Results: Among 12 polycyclic aromatic quinones, IL-8 level was about 1.3～2.1 timeshigher in 8 quinone groups than in only mite antigen group (n=3) with significance: 1,2-NphQ (500 nM), 1,4-naphthoquinone (1,4-NphQ) (500 nM),1,4-anthraquinone (1,4-AQ) (5 µM), PhQ (500 nM), 4,5-pyrenequinone (4,5-PyQ) (500 nM), 5,12-naphthacenequinone (NCQ) (5 µM), 1,4-chrysenequinone (1,4-ChQ) (5 µM), and 5,6-chrysenequinone (5,6-ChQ) (500 nM). Conclusion: The amplifying action of 8 polycyclic aromatic qui-nones in IL-8 generation induced by mite antigen were found in this study. Several polycyclic aromatic quinones may be responsible for hazard-ous effects of PM including DEP on allergic and inflammatory lung diseases. Clarification of their variation in operating points and upstreammechanisms needs future studies.

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PosterSession

PE4-9 Change in allergen sensitization prevalence in Japan between 2005 and 2017

Jun Tanaka1), Yuma Fukutomi2), Asako Kitahara1), Yoshiki Shiraishi1), Tadashi Nagai3), Tsuyoshi Oguma1), Koichiro Asano1) (Division of PulmonaryMedicine, Department of Medicine, Tokai University School of Medicine, Japan1); Clinical Research Center, Sagamihara National Hospital, Kana-gawa, Japan2); Japanese Red Cross Central Blood Institute, Tokyo, Japan3))

Background and Purpose: We previously reported that middle-aged Japanese subjects are less frequently sensitized to some allergens thanyounger ones in a general population. The aim of this study is to investigate whether the age-related decline in the prevalence of allergen sensiti-zation was dependent on aging or the difference among the generations.Methods: Stocked serum samples at blood donation to the Japanese RedCross were used for this study. Eight hundred samples obtained in 2005 from residents in Tokyo aged 20-59 years and four hundred samples ob-tained in 2017 from donors aged 20-29 and 40-49 years were randomly selected maintaining the same proportion for sex and age groups. IgE anti-bodies specific for orchard grass, alder, dust mites, Aspergillus, cedar, moth were measured by ImmunoCAP method. Results: IgE specific for or-chard grass, alder, dust mites, cedar and moth, but not for Aspergillus in the 2005 samples showed an age-dependent decline in prevalence. Spe-cific IgE for orchard grass and dust mites were present in 25% and 49% of the subjects with age 40-49 years, respectively, in 2017; the prevalenceof the specific IgE was significantly lower in the same age group of 2005 (13% and 30%), but equivalent to the prevalence in the same generation(age group of 30-39 years; 32% and 56%). On the other hand, there was no significant difference between 2005 and 2017 in the prevalence of IgE inthe age group of 20-29 years or of IgE for alder, ceder, or moth in the age group of 40-49 years. Conclusion: Age-related decline in allergen sensiti-zation is more dependent on the difference among the generation than aging effect. Sensitization pattern for orchard grass and dust mites hadchanged in Japan between those born before and after 1985.

PE4-10 Two novel allergic proteins which induce allergic asthma, from the octocoral

Yuko Kato1,2,7), Yoshiko Takeda2,4), Yukimitsu Imahara3), Seiji Kawamoto5), Yoshihito Ohba6), Kosei Shioji1) (Faculty of Science, Fukuoka University,Japan1); Tohwa Institute for Orient Studies, Tohwa University, Japan2); Wakayama Laboratory, Biological Institute on Kuroshio, Japan3); GraduateSchool of Advanced Sciences of Matter, Hiroshima University, Japan4); Hiroshima Research Center for Healthy Aging (HiHA) and GraduateSchool of Integrated Sciences for Life, Hiroshima University, Japan5); Faculty of Pharmaceutical Science, Nagasaki International University, Ja-pan6); Pharmaceutical Research Center, Nagasaki International University, Japan7))

Many fishermen especially those that catch the spiny lobster, suffer from allergic symptoms from the octocoral in Miyazaki prefecture. We havefound two species of octocoral, Scleronephthya gracillima and Dendronephthya sp. which cause the allergic disease in fishermen. One of the octo-coral was characterized as a new GFP like red fluorescent protein named Akane. Farther, Akane had the allergic protein as a molecular mass of27 kDa with ELISA test and western blotting method. In the present our study, the other octocoral Dendronephthya sp. showed also allergic reac-tion by ELISA test with the patient’s sera. These proteins from octocoral were tested by ELISA showed that the cross-reacted with the IgE of pa-tients. Keywords: octocoral, allergic protein, IgE, GFP like protein Akane Ref.1. Characterization of a novel allergenic protein from the octocoralScleronephthya gracillima (Kuekenthal) that corresponds to a new GFP‐like family named Akane, Yuko Kato, Mitsuru Jimbo, et.al, Lumines-cence, 2017 Sep;32(6):1009-1016. Ref.2. Purificationof a novel allergen (SAP-1), which induces allergic asthma, from thered soft coral (Alcyoniumgracillimum), Yoshiko Takeda, Yuko Kato, et.al. Allergology International, 49, 213-218, 2000.

PE4-11 The structure of sensitization to different allergen extracts and molecules among patients with asthma in Dnipro, Ukraine

Eugenia Dytyatkovska, Viktoriia Voloshkina, Kateryna Gashynova (Occupational Diseases and Clinical Immunology, State Establishment Dni-propetrovsk Medical Academy Ministry of Health of Ukraine, Ukraine)

Background: To study the structure of sensitization to different allergen extracts (E) and molecules (M) that cause asthma in Dnipro region,Ukraine. Methods: medical history, total serum and specific serum IgE to allergen E and M (ALEX). Results: 86 people aged 2-70 made up thestudy sample. The average total IgE was 498.4 KU/L, 58.5% of patients had an increased total IgE. 17.4% of study population had an increased to-tal IgE while specific IgE to all E and M was normal. The highest sensitization to E was to Ragweed (49.4%); Cat (17.24%); European house dustmite and Olive tree pollen (12.64%); Birch pollen and Alternaria alternata (11.49%); Latex (8.05%); Timothy grass (4.06%). The most significant sensi-tization to M was to Amb a 1 (54.02%), it was also high to Amb a 4 (17.24%). The sensitization to Fel d 1 was 24.14%. It was followed by Hev b 8 andPhl p 12 (14.94%). The sensitization to Ole e 2, Alt a 1, Bet v 1 was 12.64%. Considerable sensitization was to lol p 1, Phl p 1, Der p 2 (10.34%). Con-clusions: Calculation of total IgE level is not specific measure in diagnosis of asthma. Over 40% of patients with asthma in Dnipro region, Ukraine,have normal total IgE level according to test results. 17.4% of patients with asthma had increased level of total IgE and normal specific IgE thiscan be due to sensitization to rare allergens or the increased level of total IgE is the result of other conditions. The structure of sensitization to al-lergen molecules and extracts is similar among asthmatics in Dnipro, Ukraine. The most widespread sensitization among patients with asthma isto Ragweed. Another major cause of sensitization is Cat. Considerable sensitization is to some other pollen allergens (Birch, Olive tree, and Timo-thy grass), fungus (Alternaria alternata), and European house dust mite.

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PosterSession

PE4-12 Animal epithelial allergen hypersensitivity and correlation of clinical symptoms

Nadmid Khorloo1,2,3,4,5), Munkhbayarlah Sonomjamts2), Tuvshintur Naidansuren3), Bayar-Ulzii B4), Garid Khishigt5) (Mongolian National University ofMedical Sciences, Mongolia1); Department of Pulmonology & Allergy, Mongolian National University of Medical Sciences, Mongolia2); Departmentof Pulmonology & Allergy, Mongolian National University of Medical Sciences, Mongolia3); “Effect” Allergy Asthma hospital, Mongolia4); MonfaTrade, Mongolia5))

Background: The numbers of pet ownerships tend to increase worldwide. To study the cause and risk factors of dog, cat and horse allergiesamong the aeroallergen with comparing their age. Method: This study has conducted by hospital based cross sectional study and retrospectiveand descriptive study model. For the test (BioIC) to identify allergen-specific IgE in 154 patients, hypersensitive to cat, dog and horse allergy,questionnaire and physical examination have been carried over. Spirometry analysis was performed to confirm the diagnosis of bronchial asthmain patients who had asthma questionnaire. Result: In our study, a total of 154 participants were involved with 1-63 aged (average age 18.7±14.6).By the result of the BioIC test, cat allergy, dog allergy, horse allergy was 114 (74.02%), 52 (33.76%), 47 (30.51%) respectively. The mean sensitivityrate for cat allergic children was 14.48AU where it indicates 10.85AU in cat allergic adults (p<0.03). The mean sensitivity rate for horse allergicchildren was 7.33AU where it indicates 10.85AU in horse allergic adults (p<0.05) and 7.29AU in dog allergic children and 5.06AU in adults. Amongthe total patients who had participated were diagnosed 104 rhinitides (68.8%); 29 asthmas (18.8%); 20 urticaria (12.9%); 18 atopic dermatitides(11.6%); 7 asthma and rhinitis mixed (4.54%). The sensitivity rate for cat allergic children with asthma was 30.84±3.05AU, the sensitivity rate foradults was 14.72±2.85AU (p<0.01) which has a statistically different value. By the questionnaire test, 61 percent of participants wash their petsonce in 7 to 14 days, 65 percent of participants sleep with their pets in one room and 51 percent; they do not use a proper product to wash theirpets. Conclusion: Children has higher sensitivity rate of epithelial allergen to cat, horse and dog than adults. Leading complications of hypersensi-tivity in both children and adults were rhinitis and asthma. Analysis of allergen-specific IgE test revealed sensitivity rate for cat is higher thansensitivity to dog and horse regardless of nurturing them at home. Frequency of washing pets and sleeping in one room are becoming risk fac-tors.

PE4-13 New dot-blot methods for evaluating the effect of inactivators on mite and Japanese cedar pollen allergens

Megumi Yoshida1,2), Keijiro Mizukami1), Keigo Kurata2), Tadahiro Nasukawa1), Jumpei Uchiyama1), Masahiro Sakaguchi1) (Laboratory of VeterinaryMicrobiology I, Azabu University, Japan1); ITEA Inc., Japan2))

Background: Sandwich ELISA has been used to evaluate potential allergen inactivators. However, inactivators included in the samples affect theassay’s ability to measure allergen levels. Allergen levels measured by the ELISA may be underestimated due to the effect of the inactivator and,thus leading to overestimate the inactivation potential. In this study, to evaluate inactivators while avoiding interference with the assay’s ability,we used the dot-blot method.Methods: Each amount (4, 20, 100 ng) of mite (Der f 1) allergen was immobilized on PVDF membranes, which weretreated with each inactivator (5 ppm sodium hypochlorite, 6 M guanidine, 3.5 mM sodium lauryl sulfate (SDS)) against the immobilized allergensand washed afterwards. Next, membranes were divided into two groups, then ones were immunostained for the allergens and the others weregold stained for protein detection. For immunostaining, the allergens on the membrane were detected with anti- Der f 1 IgG monoclonal antibod-ies against the allergens. For protein detection, gold staining was performed. The same operation was carried out for Japanese cedar pollen aller-gen (Cry j 1). Results: Anti-Der f 1 IgG reactivity to allergens on the membrane was studied by using the immunostaining method. Anti-Der f 1IgG was reactive under the following conditions: 4 to 100 ng of Der f 1 with PBS treatment (no activator), 20 and 100 ng of Der f 1 with guanidinetreatment, and 100 ng of Der f 1 with sodium hypochlorite and SDS treatment. Next, protein staining was performed to confirm whether Der f 1was detached from the membrane by the inactivator. All spots (4 to 100 ng) of Der f 1 in all membranes were detected using protein staining andconfirmed that the allergen proteins were not detached from the membranes. The dot blot analysis of Cry j 1 allergen was almost the same asthat of Der f 1. Conclusion:We made it possible to accurately evaluate inactivators for allergens using the dot-blot method, which combines im-munostaining and protein detection methods.

PE4-14 Effect of Asian dust on respiratory symptoms among children with and without asthma, and their sensitivity

Hideki Hasunuma1,2), Ayano Takeuchi3), Rintaro Ono4), Yuko Amimoto5), Yoon Ha Hwang6), Itsushi Uno7), Atsushi Shimizu8), Yuji Nishiwaki9),Masahiro Hashizume10), David J Askew11), Hiroshi Odajima4) (Department of Public Health, Hyogo College of Medicine, Japan1); Center for Environ-mental Information Science, Japan2); Keio University, Japan3); National Hospital Organization Fukuoka National Hospital, Japan4); Uji-TokusyukaiMedical Center, Japan5); Busan St Mary’s Hospital, Republic of Korea6); Kyushu University, Japan7); National Institute for Environmental Studies,Japan8); Toho University, Japan9); The University of Tokyo, Japan10); University of Occupational and Environmental Health, Japan11))

Background: There has been little study on the effect of Asian dust exposure on respiratory symptoms among children who are vulnerable toenvironmental factors. In this panel study, we investigated the effect of Asian dust on respiratory symptoms among children with and withoutasthma, and their sensitivity. Methods: Children attending two elementary schools (137 total), and 23 children with asthma from cooperatingmedical institutions in Fukuoka prefecture were recruited. Subjects measured peak expiratory flow rate, and recorded asthma-like symptoms,cough, nasal symptoms and use of medication in a diary from 1 April, 2013 to June 30, 2013. To assess exposure to Asian dust, we used Light De-tection and Ranging (LIDAR) data. For the analysis of the association between Asian dust and respiratory symptoms, the case-crossover designand generalized estimating equation (GEE) models were used. Taking individual sensitivity to respiratory aggravation into consideration, the sub-jects were classified into three groups: children without asthma, children with asthma who do not use long-term preventive medication (CA) andchildren with asthma who use long-term preventive medication (CA-LTM). Results: For CA, Asian dust exposure was significantly associatedwith asthma-like symptoms, with a hazard ratio of 5.17 (95%CI: 1.02, 26.12) at Lag0, and the change in %maxPEF, -1.65% (95%CI:-2.82, -0.48) at Lag0.For children without asthma, a statistically significant association was found between Asian dust exposure and the change in %maxPEF, -0.56%(95%CI: -1.31, -0.08) at Lag1. However, no adverse effects were observed in CA-LTM. We further examined the morning-evening variation in thesub-analysis. The results showed that the decreases of %maxPEF were observed in the morning. Conclusion: This study suggests the possibilitythat long-term preventive medication to manage asthma may suppress aggravation of respiratory symptoms due to Asian dust and may be an ef-fective prevention.

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PE4-15 Link between air pollution and food allergy prevalence

Claudia H Lau1), Christopher M Warren2,3), Ruchi S Gupta2) (University of California, Los Angeles (UCLA) Mattel Children’s Hospital, USA1); LurieChildren’s Hospital, Northwestern University School of Medicine, USA2); Stanford University School of Medicine, USA3))

Background: Air pollution is strongly associated with asthma prevalence and exacerbations. Recent studies have found that particulate matterpollution changes the FOXP3 locus of Treg cells, exacerbates TH2 responses, and accumulates pathogenic memory in TH2/TH17 cells. We hy-pothesize that the effects of air pollution might extend to non-respiratory atopic diseases such as food allergy. Methods: A population-based sur-vey was administered to 51,819 US households in 2015-2016, resulting in parent-proxy and adult self-report data for 8047 California residents (3604children, 4443 adults). Established symptom-report criteria were utilized to define food allergy. Food allergy prevalence was based on responsesfrom a nationally representative, probability-based AmeriSpeak Panel (51% completion rate), which were augmented by nonprobability-based re-sponses via bias-corrected post-stratification weighting. Prevalence was estimated at the census tract level, accounted for household-level cluster-ing, and geocoded to environmental exposure data collected by the California Environmental Protection Agency. Survey-weighted multiple re-gression models evaluated associations between food allergy prevalence and mean annual pollution exposures (Ozone, diesel particulate matter,PM2.5, traffic density). Results: Spearman correlations between pollution exposure and food allergy prevalence were positive but small, rangingfrom r =.013 for Ozone (not statistically significant) to r =.025 for PM2.5 exposure (p=0.029). Food allergy prevalence was greater in communitieswith higher pollution burden. Such increased likelihood was particularly signficant (p=0.026) for PM2.5, even when adjusted for age, sex, race, andincome (ORper quartile increase=1.11; 95%CI 1.01-1.22). This corresponds to a statistically significant 2.5% difference in food allergy prevalence betweenthe 90th and 10th percentiles of adjusted modeled PM2.5 exposure (p=0.03). Although other pollution exposures demonstrated a similar trend, theregression models were not statistically significant for Ozone, diesel PM, nor traffic density. Conclusion: Our analysis demonstrates that the asso-ciation between air pollution and asthma extends to non-respiratory atopic disease such as food allergy. In addition to directly altering lung func-tion, air pollution might also indirectly alter our immune systems.

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Poster Session 5Allergy prevention and risk factors

PE5-1 Metal patch testing at Fukuoka University from 2014 to 2019: the real world for preoperative tests

Emi Sato1), Yutaro Yamasaki2), Akira Maeyama2), Akie Kajita1), Shinichi Imafuku1) (Department of Dermatology, Fukuoka University Hospital, Ja-pan1); Department of Orthopedic Surgery, Fukuoka University Hospital, Japan2))

Background: There is not enough research that demonstrated the relevancy between the preoperative metal patch testing (MPT) and the post-operative results of metal implants. However, at many hospitals in Japan, patients who have self-reported a metal allergy receive MPT beforeplacing a metal implant. The MPT gives a burden on the preoperative patient, and the result of the MPT is more or less influenced by subjectivejudgement of physicians. Furthermore, the results of MPT may influence major consequences, such as aborting surgery or changing implants.Methods: All patients who underwent MPT at Fukuoka University Hospital from January 2014 to June 2019 were analyzed. Results: 149 patientswere identified. Preoperative tests accounted for 95 (63.7%), a majority of all MPT. The departments requesting a MPT as a preoperative test in-clude orthopedics (73 cases), dental and dental surgery (17 cases), neurosurgery (2 cases), cardiovascular surgery (1 case), gastrointestinal surgery(1 case), and emergency and critical care center (1 case). In 5 of 149 cases (3.36%), the results of MPT affected the following operation. When thefive cases were re-evaluated according to the ICDRG criteria based on clinical photographs, two cases could be clearly diagnosed as positive, andthree cases were suspected to have uncertain or irritant reaction. The metals reacted in the two MPT positive cases were cobalt chromium alloy(as is) and nickel sulfate (ionized nickel). Investigation of the subsequent treatment of those affected-five patients revealed that three cases hadused alternative materials for surgery, one case had cancelled surgery, and one case was unknown. Follow-up of the current status of these 5cases revealed that 3 cases had good result at least one year, 1 case had discontinued visit to our hospital, and 1 cancelled case had been reconsid-ered a surgery due to exacerbation of symptoms. Conclusion: The result of MPT strongly affects the decision of surgeons who use metal implant.

PE5-2 Profile of Allergy: the National Picture in Vietnam

Minh Duc Nguyen Tran1), Loc Quang Le1,2), Duy Pham Le3) (Falcuty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, VietNam1); Online Research Club, Viet Nam2); Department of Immunology, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam3))

Background: Recent years have seen the increased developing economy in Asia, leading to more frequent reporting of allergic reactions in occu-pational and domestic settings. This review focuses on recorded allergic diseases and allergen sensitization profiles of Vietnamese people. Re-view: Although allergic rhinitis and asthma are global health problems, there are insufficient epidemiologic data in Vietnam. Recently, one ques-tionnaire completed by 5782 (82.5%) subjects in 2018 in shows that the prevalence of asthma among adults of 45%, in contrast to previous resultsof 2%, strongly indicates an increase in asthma among adults in Vietnam. The prevalence was, in fact, higher than expected in rural Vietnam.While the benefits for agricultural, wastewater use also poses a hazard to human health. Preliminary studies in Phnom Penh and Hanoi showed ahigh prevalence of self‐reported skin disease and suggested that exposure to wastewater is a major risk factor. In Vietnam, the clinical pictureof drug hypersensitivity reactions is rather heterogeneous, mirroring many distinct pathophysiological events. The prevalence of food allergy inVietnamese children seems to be higher than previously reported from other Asian countries with crustacean as the predominant allergy‐induc-ing food. Allergy tests are expected to be available as a supply for the rising-demanding testing material market. However, there is inaccuracyand limited access to allergic testing. Finally, there is very limited research conducted to study about allergen sensitization profiles of Vietnamese.Conclusion: The range of allergic disease is well characterised, whereas for studies of Vietnamese allergen profile the evidence is somewhat lim-ited. There is a need for further epidemiological studies to better characterise Vietnamese population. More detailed characterisation of specificprotein antigens in aerosols and associated establishment of dose-response relations for asthma development; the respective roles of study pre-senting to the whole healthy national population not only a specific of respiratory disease-related people; and the contribution of specific food aller-gens in the development of in asthma prediction and diagnosis are important areas for future research.

PE5-3 Is the widespread use of paracetamol (acetaminophen) a major cause in the development of allergic diseases, especially food,in the world?

Bernard Duburque (French Society of Alergy, France)

Several papers have been published which suggest the role of paracetamol (acetaminophen) in the onset of various allergic diseases in children.We present here a clinical case occurring in an adult. This man in his sixties, with no notable history, suffered in the past from an allergy to birchpollen without any cross allergy to fruit. Desensitization from 2005 to 2008 has proven to be lastingly effective. The notable point is that this pa-tient had not taken paracetamol for at least 30 years. In October 2013, he made an exception, and took paracetamol (2 grams/day) for two days.He has not taken any since. To his surprise, in the weeks following, a moderate allergy to fruits of the rosaceae family appeared: apples, pears, ha-zelnuts, almonds, peaches, cherries. This allergy will gradually decrease and disappears completely after two years. It is tempting to link this sud-den appearance of an allergy to fruits (rosacea) with the intake of paracetamol, however brief it may be. And to attribute its spontaneous disap-pearance to the subsequent non-taking of paracetamol. It is perilous to base a reasoning on a single case where one can invoke an effect of chance.However, the contemporaneity here is striking : we have the certainty of an absence of taking paracetamol for a very long time, and of its reintro-duction, unique, on a very specific date. This certainty is absolute because the patient we are talking about is the author of this communication.Could the unrestrained development of paracetamol consumption around the world be a major cause of the outbreak of allergic diseases, particu-larly food? When one considers the contemporaneity of the surge in sales of paracetamol in the world with the explosion of allergic pathologies,one can indeed wonder. Paracetamol appeared in the 1950s, but its use became widespread in the 1980s, due to the gradual withdrawal of aspirin.And it was also from the 1980s that food allergies began to become a big public health problem.

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PE5-4 Serum vitamin D levels mitigate fractional nitric oxide changes linked to Bisphenol A

Myongsoon Sung1,2,3), Man Yong Han2), Kyung Suk Lee3) (Department of pediatrics, Soonchunyang Univeristy Gumi Hospital, Republic of Korea1);Department of Pediatrics, CHA University School of Medicine, Republic of Korea2); Department of Pediatrics, Hangyang University Guri Hospital,Republic of Korea3))

Rationale: Vitamin D deficiency could be an important cause in the pathogenesis of allergic disease. Bisphenol-A (BPA) is an endocrine disruptorwidely used in food containers, and some studies have indicated that BPA exacerbates aggravation of asthma. Therefore, we investigate the rela-tionship of vitamin D status with BPA level and fraction of exhaled nitric oxide (FeNO) in children. Methods: This prospective cross-sectionalstudy examined 620 children (age 10-years to 12-years) from the general pediatric population who attended 11 different schools. A total of 432 chil-dren, all of whom completed the questionnaire, FeNO measurement, and skin prick test, and provided blood and urine samples, were included inthe final analysis. Results: The geometric mean serum vitamin D and urinary BPA levels were 21.1 ng/mL (95% confidence interval [CI]: 17.4-25.4)and 2.75 ng/mL (95% CI: 1.41-5.75), respectively. After adjustment for confounding, FeNO level was associated with serum vitamin D (adjusted β=-0.013, 95% CI: -0.022- -0.004, P=0.003) and urinary BPA (adjusted β=0.005, 95% CI: 0.002- 0.008, P<0.0010) levels. After adjustment for confound-ing, children with the level of vitamin D23 was associated with allergic disease (aβ, 0.244; 95% CI, 0.106 to 0.383; P=0.001), allergic poly-sensitization (aβ, 0.411; 95% CI, 0.251 to 0.570; P<0.001), and BPA level (aβ, 0.006; 95% CI, 0.003 to 0.009; P<0.001). Conclusions: The level of vita-min D is associated with the level of BPA and FeNO. Our findings suggest that vitamin D status is a significant determinant of urinary BPA andFeNO in children in the general population.

PE5-5 Comparative proteomics analysis reveals the effect of phulorotannin from Sargassum carpophyllum on activation mast cells

Takuya Matsui1), Chihiro Ito2), Toshiyuki Shibata3), Masataka Itoigawa4) (Department of Physiology, Aichi Medical University, Japan1); Faculty ofPharmacy, Meijo University, Japan2); Laboatory of Marine Food Cheistry, Mie Univeristy, Japan3); School of Sports and Health Science, TokaiGakuen University, Japan4))

Mast cells play a crucial role in inflammation such as allergic and fibrotic lesions, and their regulation can lead to inhibition of such pathologicalconditions. Recently, functional food has garnered much attention as a reliever of inflammation. Previously, we reported the isolation of com-pounds from plants such as Rutaceae, which is used as a fruit, flavoring agent, and traditional medicine, that could suppress the release of chemi-cal mediators from mast cells. Sargassum carpophyllum is an edible seaweed, commonly consumed in Japan, and known to contain phlorotannins,which are phloroglucinol polymers with reported anti-inflammatory activities. In the current study, we investigated the anti-allergic effects ofphlorotannin. Rat mast cell lines (RBL-2H3) that were pre-treated with three different phlorotannins were stimulated with dinitrophenol-humanserum albumin (DNP-HSA). The anti-allergic effects of phlorotannin on intra-cellular reactive oxygen species (ROS) levels and β-hexosaminidaserelease in activated mast cells were investigated by spectrofluorometry and enzyme assay. Additionally, to identify the varied intra-cellular pro-teins affected by phrolotannins, an iTARQ-based comparative proteomics analysis was performed between phulorotannins-pre-treated cells andcells stimulated DNP-HSA alone using liquid chromatography-mass spectrometry. Phlorotannin significantly and dose-dependently reduced β-hexosaminidase release (IC50 49 - 56 µM). At concentration of 40 µM, phlorotannin reduced the ROS levels by ～50% compared with those in cellsstimulated with DNP-HSA alone and non-stimulated cells, although the intra-cellular ROS levels did not differ between the DNP-HSA-stimulatedand non-stimulated cells. The proteomics analysis revealed that phulorotannins treatment upregulated the expression of 27 proteins and down-regulated that of 35 proteins compared with that in cells stimulated with DNP-HSA alone. These results demonstrate that phlorotannin reducesROS levels and β-hexosaminidase release, making it potentially useful for attenuating immediate hypersensitivity.

PE5-6 Factors associated with prolonged egg allergy in children: a retrospective cohort study

Kazunori Sakai1), Kenta Otsuji1), Shiro Sugiura2) (Department of Pediatrics, Okinawakyodo Hospital, Japan1); Department of Allergy and Depart-ment of Child Health, Aichi Children’s Health and Medical Center Health and Allergy, Japan2))

Background: No cohort study of egg allergy (EA) have been reported in Japan. The aim of this study is to investigate natural history of EA in Ja-pan and to identify risk factors for prolonged EA children by retrospective cohort study.Methods: One-year-old children who diagnosed as EA atOkinawa-Kyodo hospital were enrolled in the EA cohort retrospectively and followed until 6 years old. We evaluated the proportion of the chil-dren who acquired tolerance in each age and identified risk factors for prolonged EA allergy at the age of six. Results: Two hundred ten childrenwere enrolled in the cohort. The proportion of children who were released from egg elimination diet were 12.4% (2 y.o.), 33.9% (3 y.o.), 53.8% (4 y.o.),67.5% (5 y.o.) and 78.8% at 6 years old. We devided the children according to the status of EA at 6 years old into 3 groups: released group (n=134,64%), prolonged group (n=36, 17%) and drop out group (n=40, 19%). Complete avoidance (CA) of egg products and higher egg white specific IgEtiter (EW-sIgE) at 1 year old were significantly associated with prolonged EA (odd’s ratio: 13.80, 3.84, 95% confidence interval: 3.67-51.8, 1.97-7.25,respectively), however no significant associations were observed in sex and history of anaphylaxis. The proportion of prolonged EA at 6 years oldwere 74.5% of the children with CA and high EW-sIgE (17.5kUA/L and more) at 1 year old, 21.2% of CA and low EW-sIgE (less than 17.5kUA/L),12.2% of non-CA and high EW-sIgE, and 1.2% of non-CA and low EW-sIgE. Conclusions: About 80% of EA children acquired tolerance by 6 yearsold in our cohort. CA of egg products and high EW-sIgE at 1 year old were identified as risk factors for prolonged EA at 6 years old.

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PE5-7 Early-life skin barrier function and eczema development in Chinese infants

Yehao Chen1), Yee Kwan Ho1), Man Fung Tang1), Wing Hung Tam2), Ting Fan Leung1) (Department of Paediatrics, The Chinese University of HongKong, Hong Kong1); Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong2))

Background: Eczema is a common infantile skin disease in Hong Kong. Skin barrier dysfunction is a well-recognised feature of established ec-zema. A previous study showed that skin barrier abnormalities at birth and 2 months might precede the onset of eczema. Skin hydration (SH) andtransepidermal water loss (TEWL) are non-invasive measures of skin barrier function. This study aimed to evaluate whether SH and TEWLmeasured at early life were able to predict eczema risk during infancy.Method: Data from 49 Chinese healthy term neonates in our ongoing birthcohort were analysed. These Chinese babies were recruited within 48 hours after birth, regardless of any family history of allergy. Demographicsand prenatal exposures were collected from a validated questionnaire during enrollment. These babies were nursed in air-conditioned wards withtight control of indoor temperature and humidity, and these parameters were adjusted for in regression analyses. SH and TEWL were measuredover left volar forearm at 12-48 hours and one month. Eczema was diagnosed according to Hanifin and Rajka criteria. The relationship betweenSH and TEWL and eczema development was analyzed by non-parametric tests followed by logistic regression. Results: 27 (55%) of 49 babieswere males and 21 (43%) mothers suffered from some form of allergic diseases. Eight (16%) subjects were diagnosed with eczema within first 6months of life. Paired analyses indicated that SH and TEWL were significantly lower at 12-48 hours than those at one month, with SH being 9.5±5.0 vs 32.7±16.2 (p<0.001) and TEWL being 7.9±4.4 vs 10.2±5.3 (p=0.03). Neither SH nor TEWL differed significantly between infants with andwithout eczema at time points of birth (SH 10.3±6.0 vs 9.1±4.7, TEWL 8.0±4.4 vs 8.4±4.5) and one month (SH26.9±11.7 vs 34.5±17.2, TEWL 8.1±2.2 vs 10.9±5.8). Conclusions: Both SH and TEWL measured shortly after birth are lower than those at one month. In this Chinese birth cohort,neither SH nor TEWL in early life predict eczema development during infancy. (Funded by Health and Medical Research Fund [ref. 06170466],Hong Kong SAR Government)

PE5-8 Gut microbiome in early life may predispose to food sensitization in infants with atopic dermatitis

Seon Mi Jeong1), Yoon Mee Park1), So-Yeon Lee2), Bong-Soo Kim3), Dong In Suh4), Youn Ho Shin5), Kyung Won Kim6), Kangmo Ahn7), Soo-Jong Hong2)

(Department of Pediatrics, University of Ulsan College of Medicine, Republic of Korea1); Department of Pediatrics, Childhood Asthma Atopy Cen-ter, Environmental Health Center, Asan Medical Center, Republic of Korea2); Department of Life Science, Multidisciplinary Genome Institute, Hal-lym University, Republic of Korea3); Department of Pediatrics, Seoul National University College of Medicine, Republic of Korea4); Department ofPediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Republic of Korea5); Department of Pediatrics, Yonsei Universityof Medicine, Republic of Korea6); Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic ofKorea7))

Background: Several studies shows that perturbations in gut microbiota may influence a development of asthma, allergic rhinitis and atopic der-matitis (AD), but far less have evaluated the impact of the microbiome on the atopic dermatitis with food sensitization. We investigated whethergut microbiota at 6 months of age could be associated with AD with food sensitization at age 1.Methods: The composition of 143 infants (6-month-old) gut microbiota by pyrosequencing was analyzed fecal samples from Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA)study. Food sensitization was defined as having a positive IgE (0.35 kU/L) to milk or egg at 1 year of age. SCORing Atopic Dermatitis (SCORAD)index was measured at 6-months age. Results: The composition of Firmicutes, Clostridium g6, Clostridium g4 and Blautia was lower at 6 monthsof age in food sensitized AD than infants with non-sensitized control. The relative abundance Clostridium g6 was negatively correlated witheosinophil (rho=-0.305, P=0.011). Conclusion: Gut microbiota in early life may be associated with food sensitization in infants with AD. Key word :Gut microbiome, food sensitization, atopic dermatitis Acknowledgments: This research was supported by the Bio & Medical Technology Devel-opment Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (2017M3A9F3043834). This research wassupported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Sci-ence & ICT (NRF-2017R1A2B4006837) and the Korea Centers for Disease Control and Prevention. (2008-E33030-00, 2009-E33033-00, 2011-E33021-00, 2012-E33012-00, 2013-E51003-00, 2014-E51004-00, 2014-E51004-01, 2014-E51004-02, 2017-E67002-00 and 2017-E67002-01)

PE5-9 Impact of vitamin D deficiency on development and current symptom of allergic diseases

Yuki Okada, Takanori Imai, Toshinori Nakamura, Mayu Maeda, Taro Kamiya, Katsumi Mizuno (Department of Pediatrics, Showa University, Ja-pan)

Background: Vitamin D deficiency (VD) may influence the development and exacerbation of allergic diseases. We aimed to evaluate its impact bycomparing Japanese children from two areas with different annual UV exposures. Methods: From December 2018 to January 2019, we cross-sectionally investigated children aged between 6 and 12 years randomly selected from all school in Ogasawara or a single school in Shinagawa.VD was defined as less than 20 mg/dl of serum 25OHD level. The lifetime and current prevalence of bronchial asthma (BA), atopic dermatitis(AD), and allergic rhinitis (AR) were evaluated using the international study of asthma and allergies in childhood questionnaire. Children’s charac-teristics, perinatal environment, current eating and outdoor exercise habits were obtained and utilized for the adjustment of the effect. Categori-cal values were compared using the chi-square test. Logistic regression analysis was applied to evaluate the impact. Results: 56 and 40 childrenwere included in Ogasawara and Shinagawa, respectively. Between the areas, there were no significant differences in age and gender. The lifetime prevalence in Ogasawara and Shinagawa were BA: 23 (41.1%) vs. 18 (46.2%), p=0.62, AD: 14 (25.5%) vs 10 (25.0%), p=0.96, and AR: 29 (51.8%) vs29 (72.5%), p=0.04; The current prevalence were BA: 10 (17.9%) vs 5 (12.5%), p=0.48, AD: 10 (17.9%) vs. 9 (22.5%), p=0.57, and AR: 29 (53.7%) vs 27(67.5%), p=0.18. VD prevalence was significantly lower in Ogasawara (1 (1.8%) vs 15 (37.5%), p<0.001). Univariate analysis showed VD had no sig-nificant effect on the lifetime prevalence (OR [95%CI]: BA: 0.76 [0.54-1.09], AD: 1.19 [0.87-1.62], AR: 1.00 [0.71-1.40]), neither on the current symptoms(BA: 0.91 [0.70-1.20], AD: 1.17 [0.87-1.56], AR 1.11 [0.79-1.58]). None of the effects was significant in multivariate analysis. Conclusions: This studyshows that VD may limited impact on the onset or current prevalence of allergic diseases.

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PE5-10 Kawasaki disease, specific intractable diseases and cancers in Japan began to increase in their occurrence during 1978-86, andare categorized as pollen diseases

Akira Awaya1), Yoshiyuki Kuroiwa2) (Dermatology & Epidemiology Research Institute (DERI), Japan1); Department of Neurology, Teikyo Univer-sity Mizonokuchi Hospital, Japan2))

Systemic vasculitis such as Kawasaki Disease (KD), Takayasu arteritis (TAK), granulomatosis with polyangiitis (GPA), and periarteritis nodosa(PN), and collagen diseases such as systemic lupus erythematosus (SLE), rheumatoid vasculitis, scleroderma, and pemphigus have been suggestedto be related to pollen scatter level (PSL) in Japan. To elucidate the effects of PSL on outbreaks of gastrointestinal diseases including inflammatorybowel diseases (IBDs) and various cancers. We analyzed national database on annual occurrence of ulcerative colitis (UC), Crohn’s disease (CD),primary biliary cirrhosis (PBC), fulminant hepatitis (FH), severe acute pancreatitis (SAP), interstitial pneumonia (IP), amyloidosis (AMY), idiopathicthrombocytopenic purpura, aplastic anemia, and lung, stomach, colorectal, pancreatic, and breast cancers. Results: PSL in Japan started to in-crease during 1977-1987, characterized by three peaks (1978-79, 1982, and 1984-86), with which triphasic outbreaks of KD coincided. The PSL in1984-86 was the earliest peak with which simultaneous increase in occurrence of UC, CD, and FH coincided. Simultaneous outbreaks of UC, CDand FH coincided with subsequent four PSL peaks in 1997-98, 2000-03, 2008-09, and 2011. We found statistically significant correlations forscleroderma, GPA, PN, UC, CD, and IP between the annual number of newly registered patients in the patient-registry (P-R) year and annual PSLin the same year as P-R. Significant correlations were also shown between the number of newly registered patients in the P-R year and annualPSL measured 2-7 years (all cancers or for lung, pancreatic, and breast cancers), 6 years (TAK, rheumatoid vasculitis, scleroderma, pemphigus,UC, CD, PBC, SAP), 9 years (scleroderma, GPA, PN, UC, CD, IP), and 11 years (UC, CD) before the P-R year. Discussion: The number of newly reg-istered patients for IBDs and cancers was highly correlated with PSL 2～10 years before P-R year. Cumulative effects of PSL during a decade ormore before diagnosis of IBDs and cancers might trigger onset of IBDs and cancers when cumulative effects of PSL as environmental stress over-whelmed immunoreactive threshold. This is the first communication of association between PSL and incidence of cancers.

PE5-11 Characteristics of atopic dermatitis in Vietnamese children―a web-based survey

Duy L Pham1), Duc M Tran1), Loc Quang Le1), Tu HK Trinh2) (Medicine Faculty, University of Medicine and Pharmacy at Ho Chi Minh City, VietNam1); Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam2))

Background: Atopic dermatitis (AD) is a common allergic disease in children, characterized by chronic, relapsing inflammation with eczematousand pruritic skin condition. Clinical manifestations of AD are affected by multiple factors, including age, environmental factors, food, and skincareroutines. This survey investigated the features of AD in Vietnamese children. Methods: A web-based survey was conducted with 352 responsesfrom parents whose children were diagnosed with AD by doctors. Results:Most responders (89.5%) had their children diagnosed with AD at theage of 0-36 months (23.2% under 1 month, 53.6% of 1-12 months, and 12.7% of 12-36 months). Overall, the AD lesions were found mostly on cheeks(60.2%), leg (40.1%) and arms (39.8%). In children under 12 months of age, AD lesions were commonly found on cheeks; while lesions on arms andlegs were frequently reported in older children. 62.2% responders did not know the exact triggers of AD or thought that it was spontaneously ex-acerbated. The common suspected triggers were extreme weather conditions [hot (28.9%), dry (24.5%) or cold (24%) climates], followed by milkand dairy products (18.2%), and other foods (9.9%). Regarding treatment therapies, 74.9% responders considered skin moisturizing important, fol-lowed by frequently bathing (49.9%), avoiding cow’s milk or dairy products as well as suspected foods (25.1%), and using topical steroids (20.7%).Only 8.5% and 1.9% responders thought that oral antihistamine and corticosteroids, respectively, are important in AD treatment. More than 50%of responders believed that AD is a chronic disease with flare-ups (52.5%) and will grow out (56.6%); moreover, they believed that children withAD could develop other allergic diseases later in their life (50.8%). Conclusions: AD in Vietnamese children has similar clinical characteristics withthe general children AD. Hot weather could be a potential AD trigger in Vietnamese children. The knowledge of parents about AD in their chil-dren was good. These findings suggested a reasonable application of international AD treatment guidelines in Vietnamese children, with a minorrevision due to tropical climate conditions.

PE5-12 Surgery in early infancy and the development of food allergies

Akira Iwanaga1,3), Tatsuhiro Mizoguchi1,3), Masafumi Zaitsu2,3) (Department of Pediatrics, Saga-Ken Medical Centre Koseikan, Japan1); Departmentof Pediatrics, National Hospital Organization Ureshino Medical Center, Japan2); Department of Pediatrics, Faculty of Medicine, Saga University,Japan3))

Background: Surgery in early infancy is thought to have a large effect on the immature gastrointestinal tract due to invasion of the gastrointesti-nal mucosa, mucosal atrophy associated with perioperative fasting, and administration of antibiotics. However, there are few reports on the asso-ciation with the development of food allergies. Objective: To investigate the risk of developing food allergy in patients who underwent surgery inearly infancy.Methods: The subjects were patients who underwent surgery under general anesthesia within 6 months after birth at our hospitalbetween January 2013 and December 2018. In these cases, we examined the cases in which a history of allergy was confirmed after 12 months ofage. A retrospective study was performed using medical records. Results: There were 66 cases (40 boys and 26 girls). Three cases developed gas-trointestinal allergies in neonates and infants. In these patients, surgery was performed on the first day of life with invasive gastrointestinal tract.Fourteen cases developed immediate reactions, of which 12 were hen’s eggs, 6 were cow’s milk, and 2 were wheat (with duplication). Surgery wassignificantly earlier in patients with immediate reactions (p=0.010). Patients who underwent surgery with invasion of the gastrointestinal mucosatended to develop immediate reactions (p=0.062). Furthermore, the duration of antibiotic administration tended to be longer in patients with im-mediate reactions (p=0.070). Conclusion: Invasion of the gastrointestinal mucosa is a risk of gastrointestinal allergies in neonates and infants, andimmediate reactions may be associated with early infantile surgery.

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PosterSession

PE5-13 Infant-onset atopic dermatitis and food allergies are risk factors for environmental, animal, and pollen allergen sensitization byage 2.5

Koryo Nakayama1), Shinya Yoshihara1), Yoshihide Terashi1), Noriko Kanno2), Tomoyo Matsubara3), Tomo Ishii4), Akiko Iimura5), Mari Saito6),Manabu Miyamoto7), Hironobu Fukuda8), Shigemi Yoshihara1) (Department of Pediatrics, Dokkyo Medical University, Japan1); Department of Pedi-atrics, Nishikata Hospital, Japan2); Department of Pediatrics, Dokkyo Medical University Saitama Medical Center, Japan3); Department of Pediat-rics, National Hospital Organization Tochigi Medical Center, Japan4); Himawari Children’s Clinic, Japan5); Department of Pediatrics, Haga RedCross Hospital, Japan6); Department of Pediatrics, Nasu Red Cross Hospital, Japan7); Nasu Children’s Clinic, Japan8))

Background: Recently, it has been noticed that atopic dermatitis (AD) in infants has been associated with food allergen sensitization. However,there are few prospective studies on how the environment, animals and pollen allergen sensitization occur after the age of 1 year. Therefore, weexamined whether infants who had only AD or only food allergy (FA), or both AD and FA differed in their worsening allergen sensitization from1 year to 2.5 years of age. Method: Between 2015 and 2016, 83 infants were included in the study, 40 in the AD+FA group, 22 in the only ADgroup, 17 in the only FA group, 4 in the control group were enrolled. We used MAST36Ⓡ, which measures specific IgE for 36 allergens, every sixmonths, four times until they were 2.5 years old. The number of sensitized allergen items and their classes were compared. Results: The numberof sensitized items in the AD+FA group was significantly higher than that in the only AD and only FA groups. The environmental allergens(house dust and Dermatophagoides farinae) class showed higher levels in AD+FA group than only AD and only FA groups. Conclusion: Theseresults suggest that Infants with comorbid AD and FA showed earlier sensitization to environmental allergens than those with only AD or onlyFA, and it makes specific IgE levels for environment, animals, pollen, etc allergen increasing.

PE5-14 Association between blood eosinophil-derived neurotoxin levels and the onset of allergic disease in preschool children

Yoshihide Terashi1), Masaya Kato1), Kim Chang-keun2), Shinya Yoshihara1), Koryo Nakayama1), Manabu Miyamoto1), Yusuke Ando1), Yuji Fujita1),Tomoyo Matsubara3), Shigemi Yoshihara1) (Department of Pediatrics, Dokkyo Medical University, Japan1); Department of Pediatrics, InjeUniversity-Sanggye Paik Hospital, Republic of Korea2); Department of Pediatrics, Dokkyo Medical University Saitama Medical Center, Japan3))

Background: There are very few biomarkers that can predict the onset of allergic disease. Eosinophil-derived neurotoxin (EDN) is a granule pre-sent in eosinophils that plays a role in allergic reactions. In recent years, the blood EDN level has gained attention as a possible predictor of the on-set of allergic disease. We investigated whether there is an association between blood EDN levels and the onset of allergic disease in infants.Methods: We prospectively studied 77 infants for diagnoses of food allergies or atopic dermatitis. We followed all infants until 3 years of agethrough interviews with their parents, clinical visits, and collecting blood samples every 6 months from the date of registration. We compared theblood EDN levels between infants with or without airway allergic diseases until 3 years of age. Results: Overall, 10 of 77 infants developed allergicdisease by 3 years of age. Of these 10 infants, four were diagnosed with bronchial asthma and six with allergic rhinitis. The blood EDN level inthese 10 infants (mean±standard error of the mean; 171.2±34.28 ng/ml) was significantly greater than that in the 67 infants without allergic dis-ease (81.3±10.02 ng/ml) (P<0.005). Conclusion: These results suggest that the blood EDN level is a useful biomarker for the onset of allergic dis-ease in preschool children.

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Poster Session 6Anaphylaxis

PE6-1 A case of occupational anaphylaxis caused by beer allergy

Shintaro Suzuki, Tomoyuki Kimura, Tomoki Uno, Tetsuya Homma, Akihiko Tanaka, Hironori Sagara (Division of Respiratory medicine and Aller-gology, Department of Internal medicine, School of medicine, Showa University, Japan)

Material and Method: Case is twenties’ female floor staff of bar. Since a couple of years ago, she has avoided to drink beer, because she had chok-ing like feeling after the ingestion of beer and beer tasty beverage. One day, a glass of beer which a customer spilled was splashed her face in themiddle of service at the saloon and then she had dyspnea, facial skin flare, edema of bilateral eyelids immediately. She was transferred to theemergency room and diagnosed as anaphylactic shock. Later she was examined to specify the cause. Results: FEIA using the serum showed thepresence of barley specific IgE. Skin prick test showed the positive reactions to barley, beer and the beverages containing barley malt. While thetest, the patient complained mild dyspnea and skin itching on the skin. Basophil activating test using the patient’s whole blood also showed thepositive reaction to barley, beer and the beverages contain barley malt. According to the results above, the patient was diagnosed as allergic con-tact dermatitis followed by anaphylaxis due to allergy to barley included in the beverage. The patient was instructed to avoid the direct contactto any beverages contain barley malt on the job. Finally, the patient’s workplace was converted to the office where no risk of the contact of suchbeverages by the recommend of company doctor based on our diagnosis. Report of allergy to beer is rare, considering the amount of its consump-tion in Japan. Conclusion: In Japan, low malt beer and non-alcoholic beer-tasty beverage is well distributed as well as beer. Most of them containbarley malt. The workers of restaurant, bar and saloon have a risk of sensitization to the component of beer and its related products. The allergistshould help the manager and the occupational doctor of the company where the patient is engaged in to improve the occupational environmentfor the protection from allergy.

PE6-2 A case in Japan of anaphylactic shock to mustard in an oral food challenge

Ai Kishino1), Chinami Sasaya2) (Department of Pediatrics, Tokyo Bay Urayasu/Ichikawa Medical Center, Japan1); Department of Nutrition, TokyoBay Urayasu/Ichikawa Medical Center, Japan2))

Background:Mustard allergy has been reported for many years in the world, but not in Japan. In particular, there are few reports of anaphylac-tic shock to mustard in the world. We experienced a case of anaphylactic shock in an oral food challenge test to mustard. Case: A 3-year-old boydeveloped anaphylactic shock in an oral food challenge test to mustard. At 1 year and 5 months, he developed a facial rash, lip swelling, burkingcough, and vomiting after having firefly squid with mustard. A blood test revealed an elevated level of IgE antibodies specific for mustard. Ac-cording to the ImmunoCAP (Thermo Fisher Scientific) test, specific IgE was positive for mustard (40.6 UA/ml, class 4). Since the level of IgE anti-bodies specific for mustard gradually decreased (28.6UA/ml, class 4), an oral food challenge test was performed to confirm the diagnosis. He devel-oped nausea, skin pruritus, and sneezing within 15 minutes after having 1 gram of mustard. Despite taking antihistamines, his symptoms werenot relieved. One hour after having mustard, his blood pressure decreased from 112/64mmHg to 82/34mmHg. With rapid treatment, good pro-gress was seen without complications. Conclusions: Japanese pediatrician and healthcare providers should be aware of the possibility of anaphy-laxis to mustard, as well as other countries.

PE6-3 Anaphylactic shock with cardiac arrest induced by intravenous administration of metamizole sodium during laparoscopic chole-cystectomy

Nebojsa D Videnovic1), Jovan M Mladenovic1), Milan B Filipovic1), Rasa J Mladenovic1), Valentina P Videnovic2), Milanka R Tatic1),Ranko M Zdravkovic3) (Medical Faculty, Yugoslavia1); General Hospital, Yugoslavia2); Institute of Cardiovascular Diseases, Yugoslavia3))

Introduction:We present an extremely rare case of anaphylactic reaction to metamizole-sodium without any previous cutaneous or respiratoryreactions. Case Summary: A 62-year-old female was admitted to our hospital for a pre-scheduled laparoscopic cholecystectomy. The patient de-nied symptoms of allergies to medicines, foods and other substances. During the surgery, the patient was hemodynamically and rhythmically sta-ble with gas exchange parameters in reference range. After removal of the gallbladder, elimination of intraperitoneal carbon dioxide and placingthe patient to the horizontal position, the surgery was completed. In order to prolong the analgesia into the postoperative period, metamizole so-dium injection solution (2.5g in 250ml of 0.9% sodium chloride solution) was administered postoperatively. Five minutes after administration ofmetamizole-sodium, arterial blood pressure decreased to immeasurable levels, SpO2 became immeasurable, and sharp drop of EtCO2 occurs. ECGrecealed ventricular fibrillation. No changes were observed on the skin apart from paleness, and there was no increase in intrapulmonary pres-sure. Cardiopulmonary resuscitation began immediately - external chest compression (>100/min.), mechanical ventilation with 100% oxygen, with-out PEEP. Asystole developed before attempting defibrillation. Adrenaline 1mg i.v. was administered without interruption of external chest com-pression. Additional 1mg adrenaline was administered after 5 minutes. After 8min. ECG demonstrated a wide QRS complex with palpable carotidpulse. Hemodynamic support was continued. The patient was transferred to the intensive care unit where mechanical ventilation and hemody-namic stabilization continued. Upon admission to the intensive care unit complete biochemical monitoring (Troponins and D-dimer remained inthe normal range, arterial blood pH decreased, serum lactate levels increased…), chest RTG and ECG were performed. Differential diagnostics ex-cluded acute myocardial infarction and pulmonary thromboembolism. Testing revealed elevated serum tryptase values after 1h of reaction (32.8g/L). Conclusion: The diagnosis of anaphylaxis (especially when skin changes are absent) with the development of shock during anesthesia is fur-ther complicated by anesthesia alone and differential diagnostic dilemmas. Timely and properly directed cardiopulmonary resuscitation and in-tensive care guarantee the survival of patients in these situations. Keywords: anaphylactic reaction, cardiac arrest, laparoscopic cholecystectomy

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PE6-4 A case of anaphylaxis after ingestion of alcohol beverages

Takehito Fukushima1), Koki Okabe1), Nanae Kimura1), Akiko Sugiyama1), Reiko Kishikawa1), Satoshi Honjo2), Makoto Yoshida2) (Department of Al-lergology, National Hospital Organization Fukuoka National Hospital, Japan1); Department of Clinical Research, National Hospital OrganizationFukuoka National Hospital, Japan2))

Background: Although adverse reactions after consumption of alcoholic beverages are common, anaphylaxis is rare and its mechanism is largelyunknown. Case: A 47-year-old woman complained of wheal and erythema occasionally accompanied with wheezing and dyspnea after alcoholdrinking with meal. Specific IgE was negative for foods taken prior to the symptom development, brewers’ yeast, and malt, etc. Skin prick testswere negative on alcohol beverages, while the result was positive on acetic acid, a metabolite of ethanol. Oral food challenge test with beer, sakeand whiskey induced urticaria, while no activation was observed in basophil activation tests of beer, ethanol, acetaldehyde and acetic acid. Symp-toms were induced by taking indomethacin and sodium cromoglicate acid before the alcoholic beverage challenge test, whereas any physicalmanifestations were not observed after taking rupatadine fumarate and famotidine could. Conclusion:We experienced a case of anaphylaxis withalcohol beverage consumption. Anaphylaxis to metabolites of ethanol is speculated because of the positive skin prick test on acetic acid and thenegative results on ethanol.

PE6-5 A 15-year-old female with recurrent episodes of anaphylaxis to the genus allium: a case report

Jongsoo Kim1), Yukiko Hiraguchi1), Shogo Kato2), Saki Yamada1), Hiromu Teramen1), Tomoya Shingaki1), Yusuke Kumagai1), Takahiro Kiyomasu1),Kenji Owa1), Yutaka Suehiro1) (Department of Pediatrics, Center of Allergy and Clinical Immunology, Osaka Saiseikai Nakatsu Hospital, Japan1);Nakano Children’s Hospital, Japan2))

Background: Onion, garlic, shallot, leek, Chinese chive are the plants belonging to the genus Allium. There are some reports of immediate allergyto the genus Allium, especially onion and garlic. And some allergens, such as alliin lyase, were identified. In Japan, however, very few Allium al-lergy have been reported and it’s not well known as one of causes of anaphylaxis. Herein, we describe a case of allergy to the genus Allium withrecurrent episodes of anaphylaxis. Case: The case is a 15-year-old female without any past allergic history including food allergy. She experienced10 episodes of immediate allergic reaction and 4 episodes of anaphylaxis after eating food in the past 5 months. She did not eat the same food inevery episodes of immediate allergic reaction, making it difficult to identify the food causing the allergy. We interviewed a content of the meals indetail and found she ate Allium plants (onions, leeks) every times of the episodes. Skin prick test and basophil activation test (BAT) for Alliumplants (onion, garlic, leek, and Chinese chive) were positive. Oral food challenge test for them showed also positive (skin, respiratory and abdomi-nal symptoms). These results confirmed the genus Allium was the causative allergen. Consideration: In this case, the patient ingested the samegenus but different foods (onions, leeks) every episodes of immediate allergic reaction and had been eating Allium plants for 15 years on a daily ba-sis, so we struggled to prove the caused foods. Immediate-type of the genus Allium allergy is not well known and the genus Allium may be over-looked as the caused foods. We should consider Allium allergy when patients present with episodes of unexplained anaphylaxis.

PE6-6 Fasting-induced anaphylaxis: a case report

Tomoaki Kunitsu1), Kazuo Nonomura1), Ryo Nakajima2), Yoshihiro Maruo3), Michihiro Hide4) (Department of Pediatrics, Saiseikai Moriyama Munici-pal Hospital, Japan1); Department of Pediatrics, Saiseikai Shiga Hospital, Japan2); Department of Pediatrics, Shiga University of Medical Science, Ja-pan3); Department of Dermatology, Hiroshima University, Japan4))

Background: Anaphylaxis is a severe life-threatening systemic allergy with sudden onset. Frequent anaphylactic triggers include certain foods,venom, medications, natural rubber latex, and physical factors, such as exercise, cold, heat, and sunlight. Anaphylaxis without an apparent triggeris diagnosed as idiopathic anaphylaxis. Here, we describe the first case of fasting-induced anaphylaxis. Patient Presentation and Testing: A 6-year-old boy presented to our hospital because of recurrent anaphylactic episodes. His symptoms were generalized urticaria, angioedema,erythema, cough, swelling of the throat, nausea and vomiting, abdominal pain, tachycardia, hypotension, lightheadedness, and syncope. He did nothave a history of any food allergy, atopic dermatitis, or bronchial asthma. Allergen-Specific IgE tests were positive for ovomucoid (0.57 Ua/mL),dust (10.4 Ua/mL), and mites (41.4 Ua/mL). The test was negative for other suspected foods. The exercise challenge test was also negative. C3, C4,and C1-inhibitor protein levels and CH50 were within normal range. Considering these results, he was diagnosed with idiopathic anaphylaxis. Hewas treated with the standard doses of second generation antihistamines daily, leading to a decrease in the anaphylactic episodes. Two yearslater, his mother observed that his symptoms developed only during fasting conditions. Following the informed assent signed by the patient, fast-ing challenge test was carefully performed. The test commenced after dinner and he skipped breakfast of the following day. After 16 hours offasting, he developed hives, edema of the eyes and lips, and swollen throat. After consuming bread and rice balls, his symptoms disappearedwithin 30 minutes without any medication. The patient’s plasma and intracellular histamine levels were measured during the test. Pre-anaphylaxis intracellular histamine level was 58.96 ng/mL, whereas post-anaphylaxis was 14.18 ng/mL. After the consumption of food, his intra-cellular histamine level went back to 40.51 ng/mL. We made a diagnosis of fasting-induced anaphylaxis. An increase of food consuming frequencyto prevent fasting resulted in a decrease in his anaphylactic episodes. Conclusion: Fasting triggers anaphylaxis in this case. Fasting should beconsidered as a possible cause of anaphylaxis.

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PE6-7 A case of abalone anaphylaxis in which Skin Prick Test (SPT), Basophil Activation Test (BAT) and Oral Food Challenge (OFC)were useful for diagnosis

Kazuyuki Chibana, Hiroko Morita, Yuki Ohoka, Hiroshi Ito, Nobuhiko Uchida, Yusuke Nakamura, Meitetsu Masawa, Hiroaki Okutomi,Tatsuya Yokoyama, Sayo Soda, Naoya Ikeda, Taichi Shiobara, Ryo Arai, Masaaki Miyoshi, Akihiro Takemasa, Yasuo Shimizu, Seiji Niho (Depart-ment of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Japan)

Background: Given the variety of foods are taken in at the same time, exact diagnosis of anaphylaxis of adult food allergy is often difficult. In ad-dition, when there is no commercially available specific IgE and no skin test extract is commercially available, diagnosis is more difficult. Here wereport the case of abalone anaphylaxis it was useful for diagnosis to perform SPT, BAT and OFC. Case: A 15-years-old male. When he traveledand took in lobster, abalone, bream, chicken-grunt, firefly-squid and beef steak in dinner. After bathing and asleep, he was noticed whole bodyrash and itching. As dyspnea was appeared and increased, he consulted emergency room and was prescribed histamine-receptor antagonists. Af-ter improved, he was performed a specific IgE test but it was negative as far as possible to examined. However, specific IgE for abalone was notcommercially available, so he could not confirm exact diagnosis. He was referred to our hospital for further examination. He was positive to scal-lop specific IgE, so we had recommended to him avoid abalone, because scallop was cross reacting to abalone. However, he wanted to eat abaloneand desired to admitted to our department to perform OFC for abalone. Results: First, prick to prick test for abalone was performed and found tobe positive. One abalone was sliced into 8 slices and then taken in from 1/16 of 1 slice (1/128), and then doubled every 15 minutes (1/128 to 4slices). The dose was increased in 10 steps and finally total 8 slices, one whole abalone was consumed without any problems. Using abalone extractobtained from suspend and filtered abalone in saline, BAT was performed and it was positive. Conclusion: Although this case had a type I allergicreaction to abalone, it was determined that it was possible to take up to a whole abalone. The scallop tropomyosin is 80% homology to betweenabalone. In this case, if the specific IgE antibody against scallop positive, that suggested to be positive for abalone allergy.

PE6-8 Simultaneous onset of oral mite anaphylaxis in siblings after ingesting tacos

Kota Ikari, Moeri Tuji, Masaru Kawamura, Takuya Oda, Junichiro Tezuka (Department of Allergy and Pulmonology, Fukuoka Children’s Hospi-tal, Japan)

Introduction: Oral mite anaphylaxis is a disease that can be difficult to diagnose. We experienced simultaneous onset of oral mite anaphylaxis insiblings, of which there have been little previous reports. Case: The patients were a 9-year-old and a 13-year-old who were transported to theemergency department after eating homemade tacos, with symptoms of systemic urticaria, wheezing, and drowsiness. Their symptoms weresimilar to an allergic reaction, but there was no meal that they had never eaten before, and they had no history of food allergies. Initial diagnosiswas difficult and took some time, resulting in anaphylactic shock because of the delay. We injected epinephrine intravenously, and the symptomsimproved. Later, medical history revealed that tempura flour, one of the ingredients in tacos, was stored for a long period at room temperature.We found mites in the tempura flour with 60,000 ticks/g. A blood test showed sensitization to house dust mites and increased concentrations oftryptase. The patients were diagnosed with systemic anaphylaxis (oral mite anaphylaxis) caused by food contamination with mites. Delayed diag-nosis of oral mite anaphylaxis sometimes leads to serious symptoms, especially for patients who are highly sensitive to mites, such as those withbronchial asthma or allergic rhinitis. We need to educate individuals how to safely store flour and other flour products in order to avoid oral miteanaphylaxis. Even if they have eaten it safely before, have no history of food allergies, and are unlikely to suspect an allergic reaction, it is impor-tant to consider anaphylaxis based on the symptoms outlined here and to treat it promptly.

PE6-9 A case of milk allergy that once acquired complete tolerance, but anaphylaxis began to develop later even with a small dose

Moeri Tsuji, Kota Ikari, Masaru Kawamura, Takuya Oda, Junichiro Tezuka (Department of Allergy and Pulmonology, Fukuoka Children’s Hospi-tal, Japan)

Introduction: The acquisition of food allergy to previously tolerated foods is unusual. Recent studies suggest that food-allergic patients who haveavoided a food for about a year may lead to immediate allergic reactions upon reintroduction of that food. Case: The patient was a 10-year-old boy.He was diagnosed with atopic dermatitis at age 2 and was later diagnosed as being allergic to milk, eggs, wheat, fish, walnuts, and cashew nutsbased on symptoms; evaluated specific IgE levels; and oral food challenges (OFCs). Gradual OFCs increased milk intake, allowing consumption ofup to 200 mL of milk at the age of 6 and confirming the acquisition of tolerance. The patient had acquired tolerance to eggs, wheat and fish as well.The patient began to exhibit anaphylaxis at the age of 10. Consumption of milk, wheat, or cocoa was suspected as the cause of the anaphylaxis,and he was hospitalized for examination. In an OFC, immediate allergic symptoms were induced even upon ingestion of 10 mL of milk, which wasconsidered the cause of the anaphylaxis. This was probably due to a lack of active dairy consumption at home. In this case, house dust mite (HDM)sublingual immunotherapy (SLIT) was started just before anaphylaxis. Studies suggest that oral exposure to mite allergens disrupts intestinalmucosal homeostasis and affects immune tolerance in IgE-mediated food allergies. There is no denying that this may have contributed to re-peated anaphylaxis. Conclusion: It is necessary to consider that even small amounts of food that were thought to have acquired resistance maycause anaphylaxis. In addition, the introduction of mite HDM SLIT may be involved in the acquisition of allergy to previously tolerated foods.

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PosterSession

PE6-10 A case of allergy to barley, beer and wheat-dependent exercise-induced anaphylaxis

Natsue Ioka1), Risa Tamagawa-Mineoka1), Koji Masuda2), Norito Katoh3) (Department of Dermatology, Graduate School of Medical Science, KyotoPrefectural University of Medicine, Japan1); Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University ofMedicine, Japan2); Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan3))

A 23 year-old man with a personal history of atopic dermatitis in his childhood, developed lip swelling and pharyngeal discomfort after drinkingbeer when he was 20 years old. He also had a history of unconsciousness after eating rice cereals and walking. He also had a history of pharyngealdiscomfort and urticaria after eating some bread and running. Radioallergosorbent testing for specific IgE revealed class 3 reactivity for housedust mite, barley and malt, class 1 for wheat, gluten and secale, class 0 for ω-5 gliadin. Results of skin prick tests of barley, beer, wheat, bread andraisin bread were positive. In challenge test which included bread, loxoprofen and exercise, he had wheal, cough and discomfort of dysphagia. Wediagnosed that he had type 1 allergy to barley and beer and also wheat dependent exercise-induced anaphylaxis. The case report of beer allergyis few and we think this is the first case who has both beer allergy and wheat dependent exercise-induced anaphylaxis.

PE6-11 A case of prick-to-prick test induced anaphylaxis in a patient with potato allergy

Kazuyuki Chibana, Tatsuya Yokoyama, Yuki Ohoka, Hiroshi Ito, Nobuhiko Uchida, Yusuke Nakamura, Meitetsu Masawa, Hiroaki Okutomi,Hiroko Morita, Sayo Soda, Naoya Ikeda, Taichi Shiobara, Ryo Arai, Masaaki Miyoshi, Akihiro Takemasa, Yasuo Shimizu, Seiji Niho (Department ofPulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Japan)

Background: A prick-to-prick test is a relatively safe and frequently used for as a testing to confirm a true food allergy. It has been reported thatthe frequency of inducing anaphylaxis by the skin prick test is less than 0.02%. So, skin prick test is considered to be safe and a first choice for al-lergen detecting test. Allergic reaction due to raw potatoes are mostly skin reactions, however anaphylaxis has also been reported. Here, we ex-perienced a case of anaphylaxis when she was peeling raw potatoes, but negative for potato-specific IgE for potato. When she was examined indetail, systemic anaphylaxis was induced after performing a prick-to-prick test by potato. Case: 44-year-old female. In 201X, when she was peelingthe raw potatoes during cooking, she had systemic rash, nasal discharge, sneezing, and feel dyspnea with cough were found and was transportedto emergency room. After improved, she visited general practitioner and tested, but it revealed specific IgE for potato was negative, so she wasreferred to our hospital for investigating in detail. One month later, a prick-to-prick test for was performed using raw potatoes. Within a 15 min-utes, redness and swelling even exceeding positive control were observed. Also, she had pruritus, discomfort in the throat, nausea, vomiting, anddyspnea with cough. She was hospitalized and administered mPSL 40 mg every 6 hours, and H1/H2 blocker every 12 hours. Two months laterfrom hospitalization, we attempted to re-examine the specific IgE and basophil activation test (BAT) for potato, but those were negative. Conclu-sion: Although in this case showed an immediate response to raw potato, however, specific IgE and BAT for potato were negative. It was sug-gested this reaction might not be IgE-mediated reaction. It sought to be important to recognize that even prick-to-prick test could be a risk of in-ducing anaphylaxis and it is necessary to examine the mechanisms.

PE6-12 A case of anaphylaxis to Measles-Mumps-Rubella (MMR) vaccine in an Infant with cow’s milk allergy

Rapisa Nantanee1), Pantipa Chatchatee1), Jettanong Klaewsongkram2), Supranee Buranapraditkun2), Jongkonnee Wongpiyabovorn3),Jarungchit Ngamphaiboon1), Narissara Suratannon1) (Pediatric Allergy and Clinical Immunology Research Unit, Division of Allergy and Immunol-ogy, Department of Pediatrics, Faculty of Medicine, Thailand1); Skin and Allergy Research Unit, Division of Allergy and Clinical Immunology, De-partment of Medicine, Faculty of Medicine, Thailand2); Center of Excellence in Immunology and Immune-mediated Diseases, Department of Mi-crobiology, Faculty of Medicine, Thailand3))

Introduction: Hypersensitivity reaction to measles-mumps-rubella(MMR) vaccine is infrequent. The likely causes of allergic reaction were gelatinor neomycin contained in the vaccine. Here, we present an infant with multiple food allergies including IgE-mediated reaction to cow’s milk(CMA) who developed an anaphylactic reaction after receiving a milk-containing MMR vaccine. Case Description: The patient was a 1-year-oldmale infant who had severe atopic dermatitis and multiple food allergies since 5 months old. He had a history of generalized urticaria and contacturticaria after accidental cow’s milk exposure but had never ingested gelatin. Ten minutes after the first dose of MMR vaccination (MMRⓇ; Se-rum Institute of India, Hadapsar, Pune, India), he developed severe anaphylaxis with generalized urticaria, angioedema, cyanosis and hypotensionthat needed intraosseous fluid resuscitation. Adrenaline, chlorpheniramine, and dexamethasone were given with dramatically improvement. Themanufacturer’s vaccine package inserts revealed the components of gelatin and lactalbumin hydrolysate. Skin prick test was performed and re-vealed positive reactions to MMRⓇ; (1:100 dilution)(5 mm), gelatin (4.5 mm), cow’s milk extract (7.5 mm) and negative reaction to other brand ofMMR vaccine which did not contain milk, gelatin and egg (PRIORIXⓇ; GlaxoSmithKline, 1:100 dilution). Specific IgE to cow’s milk was 53.9 kUA/Lwhile specific IgE to gelatin and latex was 0.003 kUA/L and 0.02 kUA/L respectively (ImmunoCAP, Thermo Scientific, Uppsala, Sweden). Baso-phil activation test (BAT)(FlowCAST2, Bhlman, Schnenbuch, Switzerland) to dry skimmed milk powder (100,400 ng/ml concentration) and gelatinpowder (10,40 mcg/ml) were performed. The results confirmed a positive reaction to cow’s milk with a CD63 stimulation index of 2.1 at 100 ng/mlmilk concentration, and negative to gelatin. Conclusion: Although severe allergic adverse events attributable to MMR vaccination are extremelyrare, all serious allergic reactions should be further assessed to detect the likely causative vaccine component. The clinical manifestations andBAT results strongly supported cow’s milk to be the culprit agent for this patient. Specific brand of MMR vaccine should be cautiously used in pa-tients with IgE-mediated CMA especially ones with high levels of specific IgE to cow’s milk.

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PE6-13 Two cases of onion-induced anaphylaxis

Yuki Suzuki1), Yuri Takeshita1), Fuminori Tomyo1), Hikaru Toyota1), Hirokazu Sakasegawa1), Konomi Kobayashi1), Naoya Sugimoto1),Michio Kuramochi1), Risa Shiragami2), Keisuke Aita2), Masaaki Hagiya2), Hiroyuki Nagase1), Masao Yamaguchi2) (Division of Respiratory Medicineand Allergology, Department of Medicine, Teikyo University School of Medicine, Japan1); Division of Respiratory Medicine, Third Department ofMedicine, Teikyo University Chiba Medical Center, Japan2))

We recently experienced two cases presenting anaphylaxis due to onion (Allium cepa). Case 1: 16-year-old male. At first he presented food-dependent exercise-induced anaphylaxis following ingestion of multiple foods including onion. His second exercise-induced anaphylactic episodeoccurred after he took onion plus his ordinary dishes. Onion-specific IgE was 2.15 UA/ml. Avoidance of onion and onion-containing ketchup is ef-fective; he is now free of anaphylaxis. Case 2: 29-year-old female. Her anaphylaxis developed 5 minutes after she cut onion into small pieces. Shepresented eyelid swelling followed by systemic erythema, urticaria, dyspnea and tachycardia. These symptoms improved after treatment at ER.Onion-specific IgE was 0.38 UA/ml. Her basophils failed to show histamine release against onion extract. Onion-induced anaphylaxis is rarely re-ported, and some of the reports mention onion-dependent exercise-induced anaphylaxis. Anaphylaxis induced by cutting onion has not beenknown so far. Onion is widely used for many kinds of dishes; allergy to onion needs to be taken into account when anaphylaxis occurs following in-gestion of various cooked dishes including onion.

PE6-14 The changes in patterns of anaphylaxis over 10 years and the risk factors of severe anaphylactic reactions

Hee-Kyoo Kim, Gil-Soon Choi (Department of Internal Medicine, Kosin University College of Medicine, Republic of Korea)

Background: The causes of anaphylaxis differ by region, season and environment, and the prevalence rate is increasing. This study intended toanalyze factors related to changes in clinical patterns and severe manifestations of anaphylaxis identified in a university hospital.Methods:We in-vestigaed medical records of patients diagnosed with anaphylaxis over the past 10 years retroactively. The main collection information was basicpopulation information, past history, causative materials, clinical aspect and mediality assessments, laboratory testing, and treatment content,post-progress, etc. The causative substances included food, drugs, insect venom, and exercise. The severity of disease was classified as mild tomoderate and severe. Results: A total of 177 people were analyzed, 48.6 years old in average age and 82 men (46.3%). For causative substances,drugs were 79 cases (44.6%), 55 cases (31.1%) in food, 16 cases (9.0%) in insect, and others were 27 cases (14.1%). There were 136 cases (76.8%) ofskin, 111 cases of respiratory tract, 101 cases (57.1%) of cardiovascular system and 53 cases (29.9%) of gastrointestinal tract. Severe cases were 76cases (42.9%). In comparison with the the early and late half five-year period, total number were 61 to 116 cases, the severity rate was 55.3% to32.3%, and foods in causal materials were 26.7% to 36.7%. The risk factors for severe symptoms were age (p<0.001), underlying diseases (p=0.03),drugs (p=0.01), proBNP (p=0.03), and blood total IgE levels (p=0.01). The immediate use of epinephrine in cases were 53 cases (32.1%), followed by28 cases (15.8%). Conclusion: The frequency of anaphylaxis diagnosis has been increasing continuously over the past 10 years. Food has increasedas a causative substance. Also, as a serious risk factor, old age was significant.

PE6-15 Pediatric anaphylaxis: clinical features, inducers and treatment in Latin America and Spain

Jonathan A Bernstein, Edgardo Jares, Victoria Cardona, Alberto J Lavrut, María C Díaz, María V Souza, Mara M Rocha-Feliz,Blanca Morfin-Maciel, Mario Sánchez-Borges, Iris Alé, Nelson Rosario, Pablo Slullitel, Silvana Monsell, Alicia De Falco, Pedro Piraino,Perla Alcaraz-Duarte, Oscar Calderón-Llosa, Oscar Moreno-Laflor, German Ramon, Maximiliano Gómez (SLAAI Anaphylaxis Commitee, Argen-tina)

Background: Information regarding triggers and management of pediatric anaphylaxis in our region is scarce. Methods: A cross-sectional de-scriptive study using an online questionnaire was distributed by investigators at 24 allergy units from 7 Latin American (LA) countries and Spain.Consecutive pediatric patients consulting for anaphylaxis were included from January 2019 to March 2020. Results: 171 pediatric (0-17 years old)anaphylaxis cases were reported (61.4% male, mean age 6.25 years). The most common triggers were food, 55.5%, insect stings 17.5%, drugs, 16.4%,latex, 3.5% and idiopathic 2.9%. Milk (71.6%), hen’s egg (8.4%), nuts (5.2%), and peanuts (4.2%) were the most common foods involved. Milk was theonly reported trigger in infants, and the main anaphylaxis trigger in toddlers (76.9%), followed by eggs (15.4%) and peanuts (7.7%). In the 3 to 10years old group, milk was also the main inducer (73.6%), and eggs (7.5%), peanuts, fruits, other nuts (3.8% each) and fish (1.9%) were additional trig-gers. The anaphylaxis inducers in teenagers were milk (40%), nuts (30%), seafood (20%) and fruits (10%). Fire ants were the main insects involved(86.2%), followed by bees (6.9%), wasps and black ants (3.4% each). NSAIDs were the most frequent drug involved (42.9%), followed by beta lactamantibiotics (39.3%). Severe, moderate and mild reactions occurred in 45.6%, 42.7% and 11.7% respectively. Anaphylaxis began during the first 10minutes in 73.7% of cases, 11 to 30 minutes in 12.3%, and more than 30 minutes in 9.3%. Acute treatment was performed mostly in the ED (71.9%)and hospitalization was required in 15.8% cases (2.9% required admission to an intensive care unit). Systemic corticosteroids were used in 81.9%, H1-antihistamines in 90.6%, and epinephrine in 35.1% (IM 29.2%, SC 5.8%). Conclusion: For pediatric anaphylaxis, foods were the most common trig-gers. Milk was the main food involved, particularly in younger children. Insect induced anaphylaxis was triggered mostly by fire ants. Becauseunderuse of epinephrine is common in LA, medical education should be focused toward ED pediatricians on proper anaphylaxis assessment andmanagement.

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PosterSession

PE6-16 A prefecture-wide survey on the management of anaphylaxis in public schools

Chisa Kumagai, Minako Kawamoto, Tomoko Kaneyama, Saori Kadowaki, Norio Kawamoto (Department of Pediatrics, Graduate School of Medi-cine, Gifu University, Japan; Allergy Center, Gifu University Hospital, Japan)

Background: Children spend a significant amount of time in schools, and some may face threats of allergic reactions. To confirm the current situ-ation of school policies and identify any problems in allergic schoolchildren, a prefecture-wide survey on managing allergies was conducted, andthe questions concerning anaphylaxis were analyzed.Methods: On behalf of each public elementary and junior high school in Gifu Prefecture, thenursing teachers answered a questionnaire-based survey reviewed by the ethical committee. The questionnaire consisted of items on the numberof allergic children, school policy for food allergies, and perception of nursing teachers. Results: All the schools in Gifu Prefecture responded, andthe valid response rate of each question was 65.4100%. The survey covered 561 schools (elementary schools, 364; junior high schools, 172; others,25) with a total of 160,505 schoolchildren (106,544elementary school children and 5,3961 junior high school children). The percentage of childrenwho declared each allergic disease was 6.8%, 0.7%, 4.9%, 3.1%, 18.3%, and 5.7% for food allergies, anaphylaxis, atopic dermatitis, bronchial asthma,allergic rhinitis, and allergic conjunctivitis, respectively. Approximately 0.5% students had an adrenaline auto-injector (AAI, EpiPen), and 58.1%schools had students who needed an AAI. Further, 41.7% schools required allergy treatment within a year, and 7 patients received AAI. Amongthe children who needed care in the school healthcare room, 12.1% had no previously declared food allergy (12.5% in elementary school and 11.2%in junior high school). Furthermore, among the children who needed emergency transport, 36.4% had no previously declared food allergy (44.4% inelementary school and 26.7% in junior high school). Conclusion: Schools also need to prepare the children without declared food allergies. Familymembers, healthcare providers, and schools together must help significantly to manage allergy among children at school.

PE6-17 Safety of prescription of an Adrenaline auto-injector at our hospital

Yukiko Otsuka, Tomonori Kadowaki, Yuki Okada, Kanako Maruta, Kumiko Miyazaki, Koji Tatebayashi, Michinori Funato, Hideo Kaneko (Depart-ment of Pediatrics, National Hospital Organization Nagara Medical Center, Japan)

Background: An Adrenaline auto-injector (AAI) is first line treatment for anaphylaxis, and increasing prescription of an AAI has made it possibleto treat anaphylaxis quickly. However, anaphylaxis is sometimes fatal, so it is very important to prevent it as much as possible.Methods: A retro-spective study was conducted on the safety management of 153 patients who had been prescribed AAIs for the first time in our pediatric depart-ment from January 2016 to December 2019. Results: The cases included 141 cases of immediate-type food allergies caused by cow’s milk (n=37)hen’s egg (n=33), and wheat (n=21). Exercise-related events were 10 cases, oral allergy syndrome was 1 case. There are 12 cases whose currentcausative food were different from them at the time of prescribing AAIs. At the time of prescribing AAIs, 55 cases had a history of anaphylaxis,83 cases were reason for OFC results, 10 cases were reasons for symptoms induced by inhalation or small dose, and 2 cases had high antigen-specific IgE.18 cases suffered from anaphylaxis after prescriptions of AAIs, of which 10 cases administered AAIs. One case missed to use. Inseven cases, the prescription of AAI was discontinued due to remission/mildness of symptoms, but no case induced anaphylaxis after the comple-tion. Conclusions: To perform an oral food challenge at an appropriate timing may prevent inducing anaphylaxis before and after the prescriptionof an AAI. The severity of symptoms and the thresholds of food intake have changed compared to when AAI was prescribed, and it is necessaryto check them regularly. We need to perform oral food challenge with proper timing to ensure safety.

PE6-18 Analysis of EpiPen usage in Japan based on questionnaires about food allergy accidents

Kumi Mizutani1), Erina Kato2), Ayako Saito1), Kaoru Okamoto2), Yuji Mori1), Manabu Kawai2), Yuriko Okubo2), Kenichi Tanaka3), Yoichi Nakajima2),Atsuo Urisu4), Yasuto Kondo1) (Department of Pediatrics, Fujita Health University Bantane Hospital, Japan1); Department of Pediatrics, FujitaHealth University, Japan2); Tanaka Pediatric Clinic, Japan3); Urisu Clinic, Japan4))

Back ground: Patients prescribed epinephrine autoinjector devise (EpiPenⓇ) are taught to use under any of 13 symptoms, commonly known inJapan as“Indications for EpiPenⓇ for General Public”, determined by the Japanese Society of Pediatric Allergy and Clinical Immunology WorkingGroup. Objective: Aim of this study is to clarify if patients and their caregivers can recognize allergic symptoms and use EpiPenⓇ when required,and the problem why EpiPenⓇ is not used properly during allergic accidents by analysis questionnaires. Method: Patients and caregivers an-swered questionnaires about food allergy accidents by mail and internet. Responses from January 2016 to January 2020 were analyzed. Result: Ofthe 619 cases of food allergy accident and incident collected in the responses, 292 cases had symptoms listed in the“Indications for EpiPenⓇ forGeneral Public”. 141 cases were prescribed EpiPenⓇ. 36 patients applied EpiPenⓇ before visiting ER. Of the remaining 105 patients who did notuse EpiPenⓇ even though they had more than one of the 13 symptoms, 28 received epinephrine injection in hospital. Conclusion: In most cases,EpiPenⓇ was not properly administered by patients or their caregivers outside of hospital setting. Education for patients and caregivers on howto identify symptoms of anaphylaxis and the appropriate administration of EpiPenⓇ should be considered.

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PosterSession

PE6-20 Characteristics of anaphylaxis in between children and adults: a prospective observational study

Seiro Oya1), Kosaku Kinoshita2), Hirohisa Kinoshita3) (Department of Emergency Medicine, Shizuoka Medical Center, Japan1); Department of Emer-gency and Critical Care Medicine, Nihon University Itabashi Hospital, Japan2); Department of Emergency and Critical Care Medicine, YokohamaRosai Hospital, Japan3))

Background: Anaphylaxis is a systemic, potentially fatal, allergic reaction. The certain clinical manifestation of anaphylaxis has been reported.However, the characteristics of anaphylaxis between children and adults was not discussed well, particularly in Japan. This study aimed to inves-tigate the comparison of children and adults in patients with anaphylaxis seen in the emergency department. Methods: This was a prospectiveobservational study of anaphylaxis conducted in two emergency medical center from June 2016 through May 2019. All patients who were diag-nosed with anaphylaxis in the emergency department were enrolled in this study. Data were collected regarding patient characteristics, symp-toms and signs, treatments, clinical courses, and suspected triggers. The Student’s t-test or Mann-Whitney U test was used for continuous data,and Chi-squared test or Fisher’s exact test was used for categorical data as appropriate to perform the statistical analysis. Results: A total of 302patients were finally enrolled. Of the 302 patients, children were 95 (31.5%) and adults were 207 (68.5%). In past medical history, the proportion offood allergy was higher in children (53.7% vs 29.5%, p value=0.001). Regarding the symptoms, cardiac system was frequently observed in adult pa-tients (22.7% vs 8.4%, p value=0.01). In severity, adult patients were more severe than children (19.3% vs 4.2%, p value=0.001). In terms of triggers,foods were higher in children (95.8% vs 67.1%, p value=0.001), whereas drugs were higher in adult patients (15.0% vs 2.1%, p value=0.001). Conclu-sion: In this prospective study, we found the certain clinically different manifestation in between children and adults in patients with anaphylaxis.Clinicians need to understand the characteristics of anaphylaxis by age to manage the patients optimally.

PE6-21 What are the culprits in perioperative anaphylaxis? experience from an allergy centre at Wythenshawe Hospital, United Kingdom

Su Xin Lim1), Marina Tsoumani1,2), Susana Marinho1,2), Jia Li Liau1) (Allergy Centre, Wythenshawe Hospital, Manchester University National HealthService Foundation Trust, UK1); University of Manchester, UK2))

Background: Perioperative anaphylaxis is a rare but potentially life-threatening event. Thorough investigations are required to identify theagent responsible and identify safe alternatives for future surgery. Recent data from the United Kingdom showed a change in the trend of rele-vant triggers. We aim to assess the local experience of perioperative anaphylaxis culprits at our centre. Methods: A retrospective analysis of allpatients with perioperative anaphylaxis who completed investigations at our centre from January 2016 to March 2020 were included. Data werecollected from the patient’s electronic medical records. We collected data including patient demographics, perioperative drugs or agents used, se-rum mast cell tryptase levels, previous drug allergies and whether a causative agent was identified. Allergy investigations conducted include se-rum‐specific IgE, skin prick test (SPT), intradermal test (IDT) and drug provocation test. Results: Thirty patients with perioperative anaphy-laxis were included in the study. 70% (n=21) were female patients and 30% (n=9) were male patients. Antibiotics (46.7%, n=14) were the most com-mon cause identified, followed by neuromuscular blocking agents (NMBAs) (30%, n=9) and patent blue (6.7%, n=2). There was 1 case due to thenon-steroidal anti-inflammatory drug (3.3%) and chlorhexidine (3.3%) respectively. The causative agent was not identified in 10% (n=3) of patients.None of our patients showed sensitisation to latex. Teicoplanin was the most common implicated antibiotic (26.7%, n=8), followed by co-amoxiclav(13.3%, n=4), metronidazole (3.3%, n=1) and gentamicin (3.3%, n=1). Among the 9 patients who had reactions to NMBAs, 6 (66.7%) cases were dueto IgE mediated allergy and 3 (33.3%) cases were due to atracurium non-specific mast cell degranulation. Of the 6 patients with IgE mediatedNMBA allergy, 3 patients (50%) had positive IDT to more than 1NMBA. Conclusion: Our data is consistent with the national new changing trendof causative agents in perioperative anaphylaxis with antibiotics identified as the most common culprit, followed by NMBAs. Further studies arerequired to address the diagnostic gap where a cause has yet to be identified despite current comprehensive investigations.

133

PosterSession

Poster Session 7Animal models 1

PE7-1 Macrophages produce histamine through the interaction with antigen specific Th2 cells

Naruhito Iwasaki1,2), Seigo Terawaki1), Hirokazu Sakamoto2), Kishiko Sunami2), Fuminori Tokunaga1) (Department of Pathobiochemistry, GraduateSchool of Medicine, Osaka City University, Japan1); Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, OsakaCity University, Japan2))

Background: Antigen specific Th2 cells play an important role in the pathogenesis of allergic rhinitis. Recent studies have proved that some types of macro-phages, such as M2 macrophages, are related to allergic diseases. In this study, we revealed that macrophages produce histamine through the interactionwith antigen specific Th2 cells. Furthermore, we found that histamine produced from macrophages is involved in the nasal early phase reaction in micemodel.Methods:We developed bone marrow-derived macrophages (BMDM) from WT and histidine decarboxylase-deficient Hdc-/- mice, which cannot syn-thesis histamine. DO11.10 mice-derived naive CD4 T cells, which express an OVA323-339-specific T-cell receptor, were differentiated into Th2 cells (OVA-Th2 cells) in vitro. Then, we co-cultured BMDM and OVA-Th2 cells with or without OVApep, and measured histamine concentration in the culture superna-tant. To investigate the role of histamine production in macrophages in vivo, we created mice model, which were adoptively transferred with in vitro differ-entiated OVA-Th2 cells, then nasally challenged with OVA. In addition to counting the sneezing numbers, we analyzed nasal infiltrations of eosinophils andOVA-Th2 cells using a flow cytometry. Results: In the presence of OVApep, the in vitro co-culture of WT-BMDM and OVA-Th2 cells produced 4 timeshigher amounts of histamine than that of without OVApep. In contrast, the amounts of histamine produced from co-culture of Hdc-/--BMDM and OVA-Th2cells with OVApep were markedly decreased. Moreover, OVA challenge elicited sneezing responses in OVA- Th2transferred mice, but not non-transferredmice in vivo. OVA challenge failed to elicit sneezing in OVA- Th2 transferred Hdc-/- mice. When we depleted macrophages from OVA-Th2transferred andOVAchallenged mice by intraperitoneal injection of clodronate-containing liposomes, it completely abrogated OVAinduced sneezing responses in the OVA-Th2 transfer model. Conclusions:We identified that macrophages interact with antigen specific Th2 cells through antigen, and then produce histamine. Thisnovel histamine production pathway seems to be involved in the nasal early phase reaction, and that implies a target to treat allergic rhinitis.

PE7-2 Effector T cells are able to proliferate in the presence of activated non-cognate Foxp3+ Treg cells

Yoshihiro Oya1,2,4), Hidekazu Futami2), Takuya Nakazawa2), Ryutaro Matsumura2), Hiroshi Nakajima3), Ethan Shevach4) (Laboratory of AutoimmuneDiseases, National Hospital Organization Chibahigashi National Hospital, Japan1); Department of Rheumatology, Allergy & Clinical Immunology,National Hospital Organization Chibahigashi National Hospital, Japan2); Division of Allergy and Immunology, Department of Clinical Cell Biology,Graduate School of Medicine, Chiba University, Japan3); National Institute of Allergy and Infectious Diseases/National Institutes of Health, USA4))

Background/Purpose: Inhibitory function of of Foxp3+ T regulatory cells (Tregs) has been established in allergy, autoimmune and in cancer.However, how they mediate their suppressive function remains unresolved. It is needed to understand how the multiple clones interact with eachother and are suppressed by Treg function in vivo. Methods: Two kinds of antigen-specific naive CD4 T cells (OVA specific and LCMV specific)were intravenously injected into immuno-competent syngeneic recipient mice. Both antigens peptides were pulsed on distinct DC or on the sameDC and were co-injected into the same recipient together with either kinds of antigen-specific Foxp3+ Tregs. Results:When two antigens werepulsed on separate DC, only the Teff specific to the same antigen as Treg recognize were suppressed, but the other Teffs in the same recipientwere proliferated. When two antigens were pulsed on the same DC, still, Teffs specific to the same antigen as Treg recognize were suppressed,but the other Teffs in the same recipient were proliferated in the same recipient. These results were reproduced also in the flip-flop conditions ofthe two antigens and mice. Conclusion: The suppressed Teffs and the non-suppressed proliferating Teffs were able to co-exist in the same envi-ronment even in the presence of activated Tregs. These findings could give insight into the mechanisms of T cell suppression by antigen specificTreg.

PE7-3 Identification of two distinct subpopulations among basophils in the bone marrow

Junya Ito1), Kensuke Miyake1), Shigeyuki Shichino2), Yoshinori Yamanishi1), Hajime Karasuyama1) (Inflammation, Infection and Immunity Labora-tory, Advanced Research Institute, Tokyo Medical and Dental University (TMDU), Japan1); Division of Molecular Regulation of Inflammatory andImmune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Japan2))

Background: Recent studies have illustrated versatile roles for basophils in various immune reactions, including allergic inflammation and protec-tive immunity against parasitic infections. However, it remains to be determined how basophils are differentiated and matured in the bone mar-row. Methods: We compared surface phenotype of basophils isolated from the bone marrow, spleen, and peripheral blood. Each subpopulationidentified was sort-purified and then subjected to microscopic and RNA-seq analysis, 24h-culture in vitro, or activation with various stimuli. Re-sults:We identified two subpopulations (FceRIalo CD49bhi and FceRIahi CD49bint) among CD200R3+c-Kit- basophils in the bone marrow while onlythe former was detected in the spleen and peripheral blood. The former subpopulation showed typical basophil morphology with ring-shaped nu-clei, but the latter exhibited horseshoe-shaped nuclei. RNA-seq analysis revealed that these two subpopulations displayed distinct profiles of geneexpression, and cell proliferation-related genes were downregulated in the FceRIalo CD49bhi subpopulation. These results prompted us to hy-pothesize that the FceRIalo CD49bhi and FceRIahi CD49bint subpopulations represent mature and immature basophils, respectively. In accordancewith this, 24h-culture of sort-purified FceRIahi CD49bint basophil subpopulation led to the appearance of FceRIalo CD49bhi cells, indicating that theformer basophil subpopulation is the precursor of the latter one. We then investigated the activation property of mature and immature basophilsubpopulations. Mature basophils were preferentially activated through stimulation with IgE plus antigens to produce IL-4 while immature baso-phils were preferentially activated via IL-3 and IL-33 stimulation to do so. Conclusion: We identified a novel immature-type basophil subpopula-tion which can be distinguished from mature one by different expression profile and activation property.

134

PosterSession

PE7-4 Risk management of L-Asparaginase-induced allergy: focusing on the influence of concomitant drugs

Ai Nogami-Hara1), Yuta Hori1), Chie Mitsuhata1), Koji Kajiyama1), Kentaro Susuki1), Akira Shimada2), Mitsunobu Mio1) (Laboratory of Pharmacology,School of Pharmacy, Shujitsu University, Japan1); Department of Pediatrics Hematology/Oncology, Japan2))

L-ASParaginase (L-ASP) is a key drug in the treatment of childhood acute lymphoblastic leukemia. L-ASP often causes hypersensitivity reactions.Some anti-cancer drugs, used concomitantly with L-ASP, are known to affect lymphocyte activities, although the role of such drugs on L-ASP hy-persensitivity is not known. We have reported animal and in vitro models of L-ASP allergy and showed its inhibition by anti-IgE antibody. In thisstudy, we examined the effect of cyclophosphamide (CY) and methotrexate (MTX) on L-ASP allergy. Male BALB/c mice were sensitized by L-ASP with Al(OH) 3 gel on days 1 and 15. Then, the right ears of the mice were i.d. sensitized by L-ASP. CY or MTX were i.p. injected on days 1and 13. The serum were collected on 27. Total IgE level in the serum was measured by ELISA. RBL-2H3 cells were sensitized by the serum andstimulated by L-ASP to determine β-hexosaminidase (β -Hex) release in vitro . CY enhanced both L-ASP-induced allergic ear edema and in-crease in serum IgE level at 150 mg/kg but not MTX. On the other hand, at 300 mg/kg of CY, L-ASP-induced ear edema was much lower than150 mg/kg group, though IgE concentration in the serum was as high as CY 150 mg/kg group. When RBL-2H3 cells were sensitized by anti-L-ASP serum, L-ASP challenge induced β-Hex release. Anti-L-ASP serum of CY 150 mg/kg-treated mice induced higher β-Hex release than nor-mal anti-L-ASP serum, though that of CY 300 mg/kg-treated mice did not induce β-Hex release. After removing IgG from the serum of CY 300mg/kg-treated mice using protein G Mag Sepharose, β-Hex release became higher than normally sensitized mice. From the present results, it be-came clear that CY induced biphasic effects on L-ASP allergy in mice, enhancing it at low dosage and attenuating it at high dosage. Since CY re-portedly suppresses Treg function, it may enhance Th2 response so as to alter L-ASP allergy. Focusing on differences in concomitant drug mayhelp manage risk of L-L-ASP-induces allergy.

PE7-5 Eosinophilic inflammation is involved in peritoneal fibrosis

Takehito Kobayashi1,2,3), Kohei Saito1), Toru Noguchi1), Yutaka Ueda2,4), Yoshitaka Uchida2,3), Tomoyuki Soma2,3), Kazuyuki Nakagome2,3),Hidetomo Nakamoto1), Makoto Nagata2,3) (Department of General Internal Medicine, Saitama Medical University, Japan1); Allergy Center, SaitamaMedical University, Japan2); Department of Respiratory Medicine, Saitama Medical University, Japan3); Department of Pediatrics, Saitama Medi-cal University, Japan4))

Rationale: Encapsulating peritoneal sclerosis (EPS) is a complication observed in patients with chronic renal failure, who are treated by perito-neal dialysis. EPS manifests peritoneal fibrosis and can lead to life-threatening intestinal obstruction. We have previously reported that the level offibrosis under different pH of PD solution. The result indicated that the acidity of PD solution was associated with the fibrotic response. As a pos-sible candidate factor which may be involved in the development of such peritoneal fibrosis, eosinophils are inflammatory cells generating fibroticmolecules including TGF-beta. Objective and Method: In this study, we examined the effects of modified potential of hydrogen solution on eosino-philic inflammation using a mouse model of peritonitis. Solution of pH: 3.5, 5.0, and 6.5 were injected intraperitoneally for 14 consecutive days usingBALB/c mice. On day 14, pathological evaluation was performed. Results: Eosinophil infiltration was observed in those peritoneal tissue, and itwas significantly enhanced by stimulation with pH 3.5 solution. Fibrotic change of the peritoneal tissue was also significantly recognized by pH 3.5stimulation. Thus, eosinophilic inflammation due to strong acid stimulation was associated with induction of peritoneal hyperplasia. Namely, therewas an association between fibrosis and eosinophilic infiltration in the peritonitis tissues. Conclusion: These results suggest that eosinophilic in-flammation and their associated mediators may be involved in post-inflammatory remodeling and tissue repair in peritoneum. Eosinophilic inflam-mation would be a possible therapeutic target in preventing EPS during peritoneal dialysis therapy.

PE7-6 Intranasal irradiation with narrowband-ultraviolet B suppresses nasal symptoms and up-regulation of histamine H1receptormRNA in the nasal mucosa of rat model of allergic rhinitis

Seiichiro Kamimura1), Yoshiaki Kitamura1), Tatsuya Fujii1), Hiroyuki Fukui2), Hiroyuki Mizuguchi3), Noriaki Takeda1) (Department of Otolaryngol-ogy, Tokushima University Hospital, Japan1); Molecular Studies for Incurable Diseases, Tokushima University Graduate School, Japan2); Labora-tory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Japan3))

Background: Narrowband-ultraviolet B (NB-UVB) phototherapy was clinically used for the treatment of atopic dermatitis. In the present study,we investigated the effect of intranasal irradiation with NB-UVB on nasal symptom, up-regulation of histamine H1 receptor mRNA and inductionof DNA damage of nasal mucosa in rat model of allergic rhinitis (AR). Methods: Levels of H1R mRNA of the nasal mucosa was measured usingreal-time quantitative RT-PCR, and DNA damage were evaluated using cyclobutane pyrimidine dimers (CPD) immunostaining. Results: In tolu-ene 2,4-diisocyanate (TDI)-sensitized rats, TDI provoked sneezes and up-regulation of H1R mRNA of the nasal mucosa. Intranasal pre-irradiationwith NB-UVB at doses of 600 and 1400, but not 200 mJ/cm2 significantly suppressed the number of TDI-induced sneezes and the up-regulation ofH1R mRNA. CPD-positive cells appeared in the nasal mucosa after intranasal irradiation with NB-UVB at a dose of 1400mJ/cm2, but not 200 and600 mJ/cm2. The suppression of TDI-induced sneezes and up-regulation of H1R mRNA lasted 24 h, but not 48 h after irradiation at a dose of 600mJ/cm2. Conclusions: Intranasal pre-irradiation with NB-UVB dose-dependently suppressed up-regulation of H1R mRNA of the nasal mucosa, re-sulting in the suppression of nasal symptom in AR model rats. The suppression after irradiation at a dose of 600 mJ/cm2 was reversible withoutinduction of DNA damage. There findings suggested that phototherapy with NB-UVB at a low dose could be effectively and safely applied for thetreatment of AR in a clinical setting.

135

PosterSession

PE7-7 Cyclooxygenase inhibition in mice heightens adaptive- and innate-type responses against inhaled protease allergen and IL-33

Seiji Kamijo1), Kei Matsuno4), Norihiro Harada4), Susumu Nakae5), Takehiko Yokomizo3), Hideoki Ogawa2), Shigaku Ikeda1,2), Ko Okumura1),Toshiro Takai1) (Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Japan1); Department of Dermatology and Al-lergology, Juntendo University Graduate School of Medicine, Japan2); Department of Biochemistry, Juntendo University Graduate School of Medi-cine, Japan3); Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Japan4); Laboratory of Systems Biology,Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Japan5))

Background: Cyclooxygenases (COXs) are responsible for the formation of prostanoids such as prostaglandins and thromboxanes. Nonsteroidalanti-inflammatory drugs (NSAIDs), which inhibit COX activity, provoke aspirin-exacerbated respiratory disease, and inhibition or deficiency ofCOXs exacerbates allergic asthma in murine models where ovalbumin (OVA) is used for immunization, although the mechanism has not beenfully elucidated. Environmental allergen sources, such as house dust mites, fungi, and pollen, contain proteases, which are frequently allergens.Method: In the present study, we used a protease papain as a model allergen, which is more relevant to natural allergen exposure than OVA, andexamined whether COX inhibition promotes adaptive-type and innate-type responses in IL-33-mediated protease-dependent models. Results:Wefound that NSAID treatment heightened both the adaptive-type and innate-type allergic responses against inhaled papain or rIL-33. We demon-strated that COX inhibition by NSAID treatment promoted airway inflammation, airway mucus production, airway hyperresponsiveness,antigen-specific Th development, and IgE production in the adaptive papain model and exacerbated allergic airway inflammation in the innate pa-pain model and innate IL-33 model. Conclusion: This study suggested that NSAID administration makes mice, which have been sensitized or notto allergens, more sensitive to stimulation with exogenous proteases or IL-33-inducing stimuli via involvement in IL-33-responsive Th cells andILC2. Additionally, the models described in the present study may assist in elucidating the roles and mechanisms of prostanoid-mediated regula-tion of adaptive- and innate-types of allergic airway diseases.

PE7-9 Modulatory effects of diazinon on mast cell activation

Miyoko Matsushima, Kazuko Atsumi, Moeko Ohara, Masahiro Takekoshi, Yuka Tsubosaki, Goki Inoue, Ko Iwaki, Yuki Hayashi,Teppei Yamashita, Tsutomu Kawabe (Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine,Japan)

Diazinon, one of the organophosphorus (OP) insecticides, is widely used not only in agriculture but also home and garden in Japan. We previouslyreported that diazinon induced the activation of macrophages, suggesting that diazinon can modify the pro-inflammatory response. Furthermore,it has been reported that OP insecticides, including diazinon, cause airway hyperreactivity. In this study, we focused on mast cells and investi-gated the effects of diazinon on mast cell activation. We used rat basophilic leukemia (RBL)-2H3 cells. Exposure to diazinon for 1 h inhibited mastcell degranulation induced by A23187 or IgE-cross linking. A23187-induced intracellular calcium influx was not altered by diazinon. Diazinon in-hibited Tnfa , but not Il4 gene expression induced by A23187 at the concentration of 150 µM. However, at the concentration of 15 µM, diazinonrather enhanced the expression levels of Il4 gene whereas there was little effect on Tnfa expression. These results suggested that diazinon inhib-ited degranulation and modulated cytokine expression in RBL-2H3 cells.

PE7-10 Antigen sensitization and intestinal infiltration of eosinophils by oral administration of aluminum salt as a food additive

Ayako Wakabayashi1), Atsuko Owaki1), Masumi Shimizu1), Ken Iwatsuki2), Rimpei Morita1) (Department of Microbiology and Immunology, NipponMedical School, Japan1); Department of Nutritional Science and Food Safety, Tokyo University of Agriculture, Japan2))

Background: Aluminum salts have an immunoadjuvant effects (Marrack P et al. Nat Rev Immunol 2009). Aluminum salts such as aluminum po-tassium sulfate or aluminum ammonium sulfate used as food additives may induce food allergies and allergic intestinal inflammation. In this study,we examined whether oral administration of aluminum salt triggers the damage of intestinal epithelial cells (IECs) and induces antigen-specifichyperactive immune responses and intestinal infiltration of eosinophils. Methods: C57BL/6 mice were orally administered with aluminum potas-sium sulfate or aluminum ammonium sulfate with or without ovalbumin (OVA). Innate immune cells such as IECs, dendritic cells (DCs), macro-phages and eosinophils were isolated from the small intestine of mice and analyzed by flow cytometory. T cell proliferation and OVA-specific Igproduction in mice were also assessed. Results: Oral administration of aluminum salt significantly increased dying AnnexinV+ Zombie+ cells inEpCAM+ IECs. We also observed enhanced cytoplasmic HMGB1- and IL-33-expression in both viable Zombie- and dying Zombie+ EpCAM+ IECsby the oral administration of the aluminum salt. The oral aluminum salt markedly enhanced expression of MHC class II and co-stimulatory mole-cules on CD11chi DCs and CD64+ macrophages and increased infiltration of Siglec-F+ CCR3+ eosinophils in the intestinal lamina propria (LP). Fur-thermore, oral administration of OVA plus the aluminum salt significantly enhanced proliferation of CD4+ and CD8+ T cells, secretion of IL-4 andIFN-γ, and production of OVA-specific plasma IgG1 and fecal IgA. Conclusion: These results suggest that oral administration of aluminum saltused as a food additive triggers the damage of IECs and cytoplasmic HMGB1- and IL-33-expression in the IECs. Released HMGB1 and IL-33 mayactivate intestinal DCs, macrophages, and eosinophils. Antigen-captured and activated DCs may contribute antigen sensitization and activatedeosinophils and macrophages may be involved in allergic inflammation.

136

PosterSession

PE7-11 Examination of antifibrotic effect of resolvin E series belonging to ω3 fatty acid metabolite

Masakiyo Yatomi1), Yasuhiko Koga1), Haruka Aoki-Saito1), Makiko Sato1), Tsurumaki Hiroaki1), Kenichiro Hara1), Noriaki Sunaga1),Toshitaka Maeno1), Satoshi Shuto2), Takeshi Hisada3) (Division of Allergy and Respiratory Medicine, Integrative Center of Internal Medicine,Gunma University Hospital, Japan1); Faculty of Pharmaceutical Sciences, Hokkaido University, Japan2); Gunma University Graduate School ofHealth Sciences, Japan3))

Background: Resolvin is an anti-inflammatory ω-3 polyunsaturated fatty acid metabolite that is transiently produced in vivo. In recent years, themechanism by which resolvin actively controls inflammation related to host defense has been elucidated. However, there are many unclear pointsabout the antifibrotic effect, and there are few reports on comparative studies of resolvins. Here we focused on the EPA-derived resolvin E series(RvE1, RvE2, RvE3), and examined the effects on fibrosis-forming factors using pulmonary fibrosis model mice. Methods: Using 8-week-old C57BL/6 female mice, osmotic pump was implanted and bleomycin was continuously subcutaneously injected. RvE1, RvE2, and RvE3 were intraperi-toneally administered for five consecutive days from day 0, and bronchoalveolar lavage fluid (BALF) was collected on day 14, and RNA was ex-tracted from lung tissue. Cell fraction in BALF and TGF-β1 and CTGF mRNA in lung tissue were measured. Results: The resolvin E seriesshowed a significant decrease in the number of neutrophils in BALF. In the RvE2 and RvE3 administration groups, a significant decrease in TGF-β1 mRNA and CTGF mRNA was observed as compared with the positive control group. Conclusion: The results suggest that RvE2 and RvE3may have antifibrotic effects in lung fibrosis model mice.

PE7-12 Effects of non-steroidal anti-inflammatory drugs on sensitization to the egg-white allergen ovalbumin in rats

Takahiro Fukushima1), Tomoharu Yokooji1,2), Taiki Hirano1), Yuta Kataoka1), Takanori Taogoshi1), Hiroaki Matsuo1) (Department of PharmaceuticalServices, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan1); Department of Frontier Science for Pharmacother-apy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan2))

Background: Enhancement of oral absorption of food allergens by non-steroidal anti-inflammatory drugs (NSAIDs) is considered an exacerbatingfactor in the development of food allergies. In this study, we examined the effects of NSAIDs on oral and percutaneous sensitization to egg-whiteallergen, ovalbumin (OVA), and its intestinal absorption in rats.Methods: The absorption of OVA was evaluated by measuring the plasma concen-tration of OVA after oral administration by gavage. To evaluate the effects of NSAIDs (aspirin, diclofenac, indomethacin and meloxicam) and sper-mine, an enhancer of allergen absorption, on the oral and percutaneous sensitization to OVA, plasma levels of immunoglobulin (Ig) E and IgG1 anti-bodies (Abs) specific to OVA were determined by enzyme-linked immunosorbent assay after initiation of sensitization. Results: High-dose aspirin(30 mg/kg) increased oral OVA absorption and plasma levels of OVA-specific IgE Ab compared with those observed in vehicle-treated rats. Incontrast, low-dose aspirin (3 mg/kg) exerted no changes in either absorption or sensitization. Spermine increased the oral absorption of OVA tonearly the same extent as high-dose aspirin, whereas the plasma levels of OVA-specific IgE and IgG1 Abs exhibited no significant differences be-tween spermine- and vehicle-treated rats. Among the NSAIDs, diclofenac and indomethacin enhanced sensitization to OVA, similar to high-doseaspirin, but meloxicam exerted no effects on Ab levels. In the percutaneous sensitization study, aspirin significantly increased plasma levels ofOVA-specific IgE, but the other NSAIDs did not affect it. Conclusions: High-dose aspirin enhanced both oral and percutaneous sensitization toOVA. Our study suggests that enhanced sensitization to OVA can be ascribed not to increased absorption of OVA from the intestinal tract. Al-though the mechanisms underlying this enhancement of sensitization are not clear yet, our study suggests that modification of cytokine produc-tion due to impairment of the intestinal barrier function and inhibition of cyclooxygenase-1 activity by aspirin may be involved.

137

PosterSession

Poster Session 8Animal models 2

PE8-1 Deficiency of a principal cysteine persulfide synthase aggravated airway allergic inflammation in a mouse model of asthma

Yusaku Sasaki1), Tadahisa Numakura1), Mitsuhiro Yamada1), Ayumi Suzuki1), Rie Tanaka1), Naoya Fujino1), Tomohiro Ichikawa1), Akira Koarai1),Takaaki Akaike2), Naoto Ishii3), Hisatoshi Sugiura1), Masakazu Ichinose1) (Department of Respiratory Medicine, Tohoku University Graduate Schoolof Medicine, Japan1); Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Japan2);Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Japan3))

Introduction: Asthma is a common disease usually characterized by chronic airway inflammation associated with type 2 immune responses. Asthma has been con-sidered to be an eosinophilic inflammatory disease that is caused by the adaptive immune system including type 2 T helper cells. It has been revealed that someeosinophilic inflammation is also controlled by type 2 innate lymphoid cells. Recent studies highlight cell metabolism as a crucial regulator to initiate clonal expansionand the effector differentiation of T cells. To further understand the pathogenesis of asthma and look for a new drug target, we focused on reactive persulfide species,recently recognized endogenous antioxidants. We have recently clarified that mitochondrial cysteinyl-tRNA synthetase (CARS2) is a principal cysteine persulfidesynthase (CPERS) in vivo and controls mitochondrial bioenergetics. Objective: To elucidate the roles of CARS2 and its products, reactive persulfide species, in airwayallergic inflammation like asthma. Methods: To investigate the roles of CARS2/CPERS in airway allergic inflammation, we performed in vivo experiments using amouse model of asthma. House dust mite (HDM) extracts were administered intranasally for 2 weeks to both C57BL/6 background wild-type mice and Cars2 het-erozygous deficient mice. Twenty-four hours after the last HDM challenge, bronchoalveolar lavage fluid, lung tissues and blood samples were harvested. We also per-formed ex vivo experiments using nave CD4+ T cells purified from spleens of each mouse by magnetic cell sorting and stimulated the cells under Th2-polarized condi-tion for 3 days. Results: Cars2 +/- mice showed aggravation of eosinophilic airway inflammation and enhanced type 2 immune response and hyperplasia of goblet cells.The amounts of serum IgE were increased in Cars2 +/- mice. In vitro differentiation experiments showed that heterozygous deficiency of Cars2 enhanced the activa-tion, proliferation and differentiation into Type 2 helper T cells from nave CD4+ T cells. Conclusion: Heterozygous deficiency of CARS2/CPERS in mice may exacer-bate airway allergic inflammation through enhanced activation, proliferation and differentiation into Type 2 helper T cells from nave CD4+ T cells.

PE8-2 Involvement of IL-5 produced from type 2 Innate Lymphoid Cells (ILC2) in acquisition of steroid resistance in a severe asthmamodel of mice

Takeshi Nabe, Masaya Matsuda, Hayato Shimora, Kennosuke Hashimoto, Mari Minagawa, Naoki Takemoto, Miku Nomura, Ryogo Terakawa,Maki Matsuo, Ayaka Mori, Takumi Ishikawa, Kazuyuki Kitatani (Department of Immunopharmacology, Pharmaceutical Sciences, Setsunan Uni-versity, Japan)

Background: It has been known that 5-10% of asthma patients are resistant to steroid therapy. However, mechanisms underlying acquisition ofsteroid resistance have been unclear. We have reported that when sensitized mice were challenged with a high dose of antigen, asthmatic re-sponses were resistant to dexamethasone. Objectives of this study were to elucidate whether IL-5/eosinophils are involved in the acquisition ofsteroid resistance, and which type of cells is a main source of IL-5 in the steroid resistant model.Methods: OVA-sensitized BALB/c mice were in-tratracheally challenged with OVA at 5 or 500 g/animal four times. Eosinophil infiltration into the lung was assessed by BAL after the 4th chal-lenge. Development of airway remodeling (airway epithelial thickening, mucus accumulation and subepithelial fibrosis) were histologically evalu-ated. Dexamethasone (1 mg/kg) and/or anti-IL-5 mAb (50 g/animal) were intraperitoneally administered during the challenges. ILC2 and CD4+

cells were purified from lung cells by Dynabeads and/or flow cytometer, and then stimulated with IL-33/TSLP and/or anti-CD3/CD28 to checkIL-5 production. Results: (1) Airway eosinophil infiltration, and development of airway remodeling in 5 g OVA-induced model were significantlysuppressed by dexamethasone, whereas those in 500 g OVA-induced model were not inhibited by dexamethasone. (2) Under the treatment withanti-IL-5 mAb, in which the eosinophil infiltration was strongly reduced, the steroid resistance in the development of airway remodeling waspartly but significantly cancelled. (3) ILC2 isolated from the steroid resistant model produced IL-5 in response to a combination treatment with IL-33 and TSLP, and the amount was larger than that of ILC2 derived from the steroid sensitive model. In contrast, CD4+ T cells produced merelysmall amounts of IL-5 in response to anti-CD3/CD28, and hardly responded to IL-33 and TSLP. Conclusion: It was suggested that mechanisms as-sociated with IL-5 produced from ILC2 is involved in the acquisition of steroid resistance probably through activation of eosinophils in the severeasthma model. Clinical effectiveness of anti-IL-5 and anti-IL-5Ralfa antibodies in asthma patients may be associated with improvement of sensitiv-ity to corticosteroids.

PE8-4 Deletion of elongation of very long chain fatty acids family member 6 (Elovl6) enhances OVA-induced type 2 and non-type 2 al-lergic airway inflammation in mice

Kazufumi Yoshida, Yuko Morishima, Hirofumi Sakurai, Hajime Osawa, Kai Yazaki, Mingma Sherpa, Masayuki Nakajima, Masashi Matsuyama,Takumi Kiwamoto, Yosuke Matsuno, Yukio Ishii, Nobuyuki Hizawa (Department of Pulmonary Medicine, University of Tsukuba, Japan)

Background: Elongation of very long chain fatty acids family member 6 (Elovl6) is a microsomal enzyme that specifically catalyzes the elongationof C12-16 saturated and monounsaturated fatty acids. Elovl6 expression was shown to be significantly downregulated in the skin of atopic derma-titis; however, to date, the involvement of Elovl6 in asthma has not been investigated. In the present study, we generated an OVA-inducedasthma model using Elovl6-deficient mice and evaluated whether fatty acid imbalance contributes to the development of allergic airway inflam-mation.Methods:We subcutaneously sensitized wild type (WT) and Elovl6-deficient (Elovl6-/- ) mice of C57BL/6 background with 100 µg of OVAon days 1 and 15, and challenged intranasally with 10 µg of OVA on day 29. Forty-eight hours after the last OVA challenge, the mice were sacri-ficed and evaluated. Results: As expected, the lungs of the OVA sensitized/challenged Elovl6-/- mice accumulated palmitic (16:0) and palmitoleic(C16:1) fatty acids, and contained less stearic (C18:0) and oleic (C18:1) fatty acids. Elovl6-/- mice exhibited marked inflammatory changes and en-hanced goblet cell hyperplasia in the airway epithelium compared to WT mice following OVA sensitization and challenge. Consistent with the re-sults of histopathological observation, the numbers of both eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF) and the mRNAlevels of IL-5, IL-6, IL-13, IL-17A and MUC5AC in the lungs were increased in the OVA sensitized/challenged Elovl6-/- mice when compared withcorresponding WT mice. The elevated serum levels of OVA specific IgE were also detected in the OVA sensitized/challenged Elovl6-/- mice.However, the mRNA levels of epithelial cell-derived cytokines, TSLP, IL-25 and IL-33, did not make a difference in the lungs between OVA-sensitized/challenged Elovl6-/- and WT mice. Conclusion: Our findings revealed that the deletion of Elovl6 resulted in the unbalanced fatty acidprofile in the lungs and significantly augmented type 2 and non-type 2 inflammatory responses, both of which are important in the pathogenesis ofrefractory asthma. We therefore suggest that Elovl6 may be a potential novel therapeutic target for the treatment of severe asthma.

138

PosterSession

PE8-5 Nerve growth factor exacerbates airway hyperresponsiveness via epithelial damage by neutrophils-derived singlet oxygen in amouse model of asthma with mixed inflammation

Hirohisa Ogawa1), Masahiko Azuma2,3), Aya Umeno4,5), Mayuko Shimizu1), Takaaki Tsunematsu1,7), Mayo Kondo3), Kazutoshi Murotomi6),Koichi Tsuneyama1), Yasuhiko Nishioka3) (Department of Pathology and Laboratory Medcine, Graduate School of Medical Science, TokushimaUniversity, Japan1); Research Center for Education of Health Bioscience, Graduate School of Medical Science, Tokushima University, Japan2); De-partment of Respiratory Medicine and Rheumatology, Graduate School of Medical Science, Tokushima University, Japan3); Health Research Insti-tute, National Institute of Advanced Industrial Science and Technology, Japan4); Department of Ophthalmology, Shimane University Faculty ofMedicine, Japan5); Biomedical Research Institute, Advanced Industrial Science and Technology, Japan6); Department of Oral Molecular Pathology,Graduate School of Medical Science, Tokushima University, Japan7))

Background: Bronchial asthma is an obstructive respiratory disease caused by allergic airway inflammation due to Th2 reactions. Refractoryasthma has recently become a problem and the several contributing factors including neutrophils have been reported. We previously reportedthat nerve growth factor (NGF) involved in neurogenic allergic inflammation and airway hyperresponsiveness (AHR). Therefore, we focused onthe relationship between neutrophils and neurogenic allergic inflammation as a mechanism of refractory asthma. In this study, we examined theroles of neutrophils and NGF in the mechanisms of refractory asthma using a mixed neutrophil infiltration model.Material and Methods:We es-tablished a chronic mixed mouse model of asthma using intranasal house dust mite antigen sensitization. After euthanized, AHR, NGF productionand hyperinnervation in lungs were examined. Singlet oxygen marker, 10- and 12-(Z, E)-hydroxyoctadecadienoic acids (HODE) in the lungs weremeasured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: NGF production and hyperinnervation were increased inthe mixed model of asthma compared to an eosinophilic model. AHR was positively correlated with NGF concentration in the mixed model ofasthma. These asthmatic parameters were inhibited by NGF neutralizing antibody, IL-17 neutralizing antibody and myeloperoxidase (MPO) in-hibitor. 10- and 12-(Z, E)-HODE as a singlet oxygen marker were increased in the lungs of the mixed model of asthma. 10- and 12-(Z, E)-HODEwere positively correlated with MPO activity and NGF production. In vitro, NGF was produced by bronchial epithelial cells stimulated by singletoxygen. Conclusions: Present findings suggested that singlet oxygen-derived oxidative stress produced by neutrophil MPO may be related toNGF-derived airway hyperresponsiveness.

PE8-6 BALF Lysophosphatidylcholine (16:0) is a possible universal biomarker for bronchial asthma by several mouse model

Yusuke Nakamura1), Yasuo Shimizu1), Yasuhiro Horibata2), Yusuke Kitazawa3), Nobuhio Uchida1), Hiroko Morita4), Ryo Arai1), Kazuyuki Chibana1),Akihiro Takemasa1), Kenjiro Matsuno3), Hiroyuki Sugimoto2) (Department of Pulmonary Medicine and Clinical Immunology, Dokkyo UniversitySchool of Medicine, Japan1); Department of Biochemistry, Dokkyo Medical University, Japan2); Department of Anatomy (Macro), Dokkyo MedicalUniversity, Japan3); Department of Respiratory Medicine, Kanazawa University, Japan4))

Background: Lysophosphatidylcholine (LPC) is physiologically active phospholipid that associate with eosinophil migration and relate to allergydiseases including bronchial asthma. The purpose of this study is to elucidate LPCs in several BA mouse model. Methods: Ovalbumin, alternariaand IL-33 BA mouse model was prepared and BALF, serum and lung tissue’s phospholipids are measured by liquid chromatography-mass spec-trometry. Similarly, cigarette smoking (CS) mouse model was also analyzed. Results: Ovalbumin, alternaria and IL-33 BA mouse presented eosino-philic in BALF. LPC (16:0) was increased in all BA model mouse group. LPC (16:0) was not in lung tissue and serum. CS mouse BALF also showedslightly elevated LPC (16:0) compared with BA mouse. Conclusion: BALF LPC (16:0) could be a good universal biomarker in BA mouse model.

PE8-7 Comprehensive gene expression analysis using RNA-seq in airway of alternaria-induced asthma mice model

Hideki Inoue, Megumi Matsuda, Kaho Akimoto, Megumi Jinno, Teru Haba, Tetsuya Homma, Shin Ohta, Shintaro Suzuki, Akihiko Tanaka,Hironori Sagara (Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University, Japan)

Background: Alternaria inhalation induces airway epithelial damage by its protease activity, which leads to eosinophilic airway inflammation, ex-cessive mucus secretion, and airway remodeling in allergic asthma mice model. Comprehensive gene expression analysis in mice airway upon al-ternaria exposure has not been conducted.Methods:Mice received an intranasal instillation 20 µL of 50 µg alternaria extract or PBS (n=3, respec-tively). Each mouse received the intranasal administration of alternaria or PBS twice a week for 6 weeks. For RNA-seq analysis, trachea and cen-tral brochi were resected and immediately immersed with RNAlater. Total RNA was extracted using RNeasy-Mini spin column as manufacture’sinstruction. RNA concentration and RNA Integrity Number (RIN) was measured using 2200 TapeStation (Agilent). Sequencing was performed us-ing NovaSeq 6000 (Illumina). The expression data were normalized using transcripts per million (TPM). Differentially expressed genes (DEGs)were identified by using threshold of 1.5 fold-change and adjusted P -value less than 0.05. Pathway analysis was performed using Gene Set Enrich-ment Analysis (GSEA). The gene expression analysis was performed by Genble Inc., Fukuoka, Japan. Results: There were 403 up-regulated and108 down-regulated genes after 6-week alternaria exposure. Most significant up-regulated genes were IGHG1, MCPT1, and Ighv1-54 with P -valueless than 1E-06. Those of down-regulated genes were SFTPA1, SPRR2F, SPRR2D, and FLG with P -value less than 0.05. In Gene Ontology (GO)analysis, up-regulated gene functions were immunoglobulin receptor binding, immunoglobulin production, inflammatory response, and T cell acti-vation. Down-regulated gene functions were keratinization, cellular response to interferon-beta, and defense response to other organism. GSEArevealed positive enrichment of several pathways including T cell receptor complex, mast cell activation, and immunoglobulin receptor binding,and negative enrichment of several pathways of keratinization, desmosome, myofilament in alternaria exposure mice relative to control one. Con-clusion: RNA-seq analysis reveals that alternaria exposure induces immune reaction related inflammatory response and impaired defense mecha-nisms in mice airway epithelium. The control for abnormal airway inflammation and restoration of epithelial barrier might be a treatment strat-egy for fungus-induced allergic asthma.

139

PosterSession

PE8-9 Repeated inhalation of salbutamol induced the development of M2 macrophages in OVA-induced mouse model of asthma

Megumi Jinno, Shin Ohta, Haruna Sato, Tomoki Uno, Yoshitaka Uchida, Tomoyuki Kimura, Kuniaki Hirai, Yoshito Miyata, Yasunari Kishino,Hideki Inoue, Tetsuya Homma, Mayumi Yamamoto, Sojiro Kusumoto, Yoshio Watanabe, Shintaro Suzuki, Akihiko Tanaka, Hironori Sagara (De-partment of Medicine, Division of Respiratory Medicine and Allergology, Showa University, Japan)

Background: It is well known that treating with β2 agonist alone as a maintenance treatment, worsen the clinical condition of asthma. However,the mechanism is still unclear. The purpose of this study is to investigate whether bronchodilation caused by salbutamol inhalation induce the de-velopment of M2 macrophages and airway inflammation in mouse model of asthma.Methods: Groups of mice (Balb/c, female) were sensitized andchallenged with OVA to generate the asthma model. After the last OVA challenge, the mice were treated with salbutamol by nebulizer twice aday for 7 days. Twenty-four hours after the last salbutamol treatment, BALF and lung tissue were collected. The number of total and differentialcells in BALF was counted. Whole lung cells were harvested from the lung tissues. The lung cells were analyzed by flow cytometry to investigatethe number of CD68 positive macrophages and expression of Arginase-1 and Relm-α, which are markers for M2 macrophages. Additionally, his-tological analysis was performed with lung tissues. Results: The total cells, macrophages and eosinophils in BALF were significantly induced inOVA-sensitized and challenged mice before salbutamol treatment compared with control mice. In addition, this model also induced goblet cellmetaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, the the number of BALF total cells,macrophages and eosinophils were significantly decreased and airway inflammation was reduced in both with and without salbutamol treatment.The lung cells were gated by CD68 positive cells, and analyzed the expression of Arginase-1 by mean fluorescence intensity. The expression ofArginase-1 was significantly induced in salbutamol treated mice compared to control mice and OVA-sensitized and challenged mice. Additionally,the thickness of airway smooth muscle was significantly increased and also the percentage of goblet cells was induced in salbutamol treated micecompared to untreated mice. Conclusion: These results indicate that the repeated bronchodilation by salbutamol inhalation induced the develop-ment of M2 macrophage and worsen the airway remodeling in mouse model of asthma.

PE8-10 Establishment of a human severe asthma model using humanized mice

Shiho Yamada1), Shuichiro Maruoka1), Asami Fukuda1), Yusuke Kurosawa1), Shota Toyoshima3), Yoshimichi Okayama3), Ryoji Ito2), Mamoru Ito2),Yasuhiro Gon1) (Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Japan1); Central Insti-tute for Experimental Animals, Japan2); Allergy and Immunology Research Project Team, Research Institute of Medical Science, Nihon Univer-sity School of Medicine, Japan3))

Background: Asthma is the chronic airway inflammation and characterized by variable airway constriction and coughing as clinical symptoms.Although inhaled corticosteroids are effective treatment for asthma, 10% of asthmatics called‘severe asthma’, who have corticosteroid resis-tance, are profoundly impaired by uncontrolled and frequently exacerbated asthmatic symptoms. In recent years, IL-33 and thymic stromal lym-phopoietin (TSLP), derived from the bronchial epithelial cells, have been reported to be involved in corticosteroid resistance in the mouse model ofasthma, and attention has been paid to the pathogenesis of severe asthma regulated by innate immunity. Although murine models have enabledinvestigation of the pathogenic role of inflammatory cells, few in vivo models recapitulate the corticosteroid resistant asthmatic responses medi-ated by human immune cells. Humanized mice are widely used for investigation of various immune diseases. The aim of this study is to establish ahuman severe asthma model using IL-3/GM-CSF/IL-5 triple transgenic mice (Triple-Tg mice) that possess human immune cells.Methods: At the14th to 18th week after humanization of Triple-Tg mice, human IL-33 and/or human TSLP was intratracheally administered at day 1 to 3, anddexamethasone or PBS was intraperitoneally administered at day 0 to 3. We collected bronchoalveolar lavage fluids (BALFs), lung tissues tomeasure airway eosinophilia, mucus overproduction and cytokines at day 7. Results: Administration of the humanized mice with hIL-33 signifi-cantly increased in the number of human eosinophils (h eosinophils) and human IL-5 (hIL-5) in the BALFs. Dexamethasone suppressed these hIL-33-induced accumulation of h eosinophils and h IL-5 in the BALFs. By contrast, dexamethasone did not suppress hIL-33-induced accumulation of heosinophils and hIL-5 in the BALFs of hIL-33 and hTSLP-administrated mice. Conclusions:We developed a novel human severe asthma model us-ing hIL-33 and TSLP-treated humanized mice. The humanized mice model reported herein will improve our understanding of the pathophysiol-ogy of steroid resistance and facilitate the preclinical development of new therapeutics for human severe asthma.

PE8-11 Differential role of TLR4 in distinct induction of house dust mite-mediated allergic airway inflammation

Takashi Ishii1,2), Yusuke Murakami1), Tomoya Narita1), Hiroki Nunokawa1), Takahide Nagase2), Naomi Yamashita1) (Department of Pharmacother-apy, Research Institute of Pharmaceutical Sciences, Musashino University, Japan1); Department of Respiratory Medicine, Graduate School ofMedicine, The University of Tokyo, Japan2))

Background: Previous studies revealed toll-like receptor 4 (TLR4) has a crucial role in house dust mite (HDM)-mediated allergic airway inflamma-tion. However, it remains to be elucidated whether TLR4 has consistently exhibit aggravated role in asthma. In this study, we clarified the role ofdifferential role of TLR4 in the pathogenesis of HDM-induced allergic airway inflammation. Methods: C57BL/6N and TLR4KO mice were sub-jected to intranasal instillation of HDM extract on distinct schedules (short-term and long-term with high dose, long-term with low dose). Bron-chial alveolar lavage fluid (BALF) and lung tissue were collected. Extracted mRNA was examined using qPCR. In some experiments, functions ofCD11b+ Gr-1+ myeloid-derived suppressor-like cells (MDSCs) and dendritic cells (DCs) were measured. Expression of mediators were also evalu-ated in primary airway epithelial cells (AECs) stimulated by HDM extract. Results:While TLR4KO mice exhibited suppressed airway inflamma-tion compared with WT mice in short-term model, aggravated inflammation was observed in long-term with high dose model and almost equiva-lent inflammation in long-term with low-dose model. Mediators in TLR4KO AECs were suppressed compared with WT. IL-13 concentration inBALF was elevated in TLR4KO, long-term with high dose model. Although DC function was comparable between wild and TLR4KO, MDSCsfrom TLR4KO showed suppressed IL-10 expression in long-term model. Conclusion: TLR4 may play a distinct role in HDM-induced airway in-flammation, which depends on the dose and period of HDM sensitization, in addition, depends on cell types.

140

PosterSession

PE8-12 Regulatory effect of fungal oligonucleotide in a mouse model of bronchial asthma through suppressing Th2 immune response

Shugo Suzuki1), Tomomitsu Miyasaka2), Ko Sato3), Jun Kasamatsu3), Keiko Ishii1), Kaori Kawakami2), Tomoko Takahashi2), Isao Ohno4),Kazuyoshi Kawakami1,3) (Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Ja-pan1); Division of Pathophysiology, Department of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan2); Departmentof Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, Japan3); Center for Medical Education, Faculty ofMedicine, Tohoku Medical and Pharmaceutical University, Japan4))

Objective: Shifted Th1/Th2 immune balance toward Th2 response is deeply involved in the pathogenesis of allergic type bronchial asthma, andtherefore, modulation of this balance toward Th1 response has been expected as an alternative strategy for a novel therapy of this disease. Previ-ously, we found a novel Th1 immunostimulating oligodeoxynucleotide (ODN) in a fungal yeast cells, Cryptococcus neoformans , named ODN112,which contains a cytosine-guanine (CG) sequence, but not any canonical CpG motif. In this study, we examined the effect of ODN112 and controlODN without any immunomodulatory activity, ODN112GC or ODN123, on Th2 immune response and development of bronchial asthma in amouse model. Methods: C57BL/6 mice were sensitized intraperitoneally with OVA and Alum and then challenged intratracheally with OVAtwice with one day interval. Mice were treated intratracheally with ODN112, ODN112GC or ODN123, or CpG1826, a classical immunomodulatoryCpG-ODN, at the challenge phase. Airway hyperresponsiveness, number of eosinophils in BALF, airway mucin production, synthesis of variouscytokines in lungs, and production of antigen-specific IgE and IgG1 were analyzed. Results: In mice treated with ODN112 as well as CpG1826, butnot with control ODN, airway hyperresponsiveness, eosinophil infiltration, mucin production, and synthesis of Th2 cytokines and OVA-specificIgE/IgG1 in lungs were decreased, whereas opposite results were obtained in the synthesis of Th1 cytokines. Additionally, in ODN112-treamedmice, inflammatory responses were milder than those in CpG1826-treated mice. Discussion: These results showed that ODN112 as well as CpG1826 improved Th2 immune response and development of bronchial asthma and suggest that ODN112 could be a candidate agent for the novelimmunotherapy in this disease.

PE8-13 Examination by age of mice in Df -induced asthma model

Shin Ohta, Tomoko Kawahara, Hatsuko Mikuni, Tomoki Uno, Haruna Sato, Yoshitaka Uchida, Tomoyuki Kimura, Megumi Jinno, Yoshito Miyata,Kuniaki Hirai, Yasunari Kishino, Hideki Inoue, Tetsuya Homma, Mayumi Yamamoto, Yoshio Watanabe, Sojiro Kusumoto, Shintaro Suzuki,Akihiko Tanaka, Hironori Sagara (Department of Medicine, Division of Respiratory Medicine and Allergology, Showa University, Japan)

Background: It has been known that majority of the patients develop bronchial asthma for the first time in childhood or young to middle-aged.However some of the patients develop asthma in elderly aged. The pathogenesis of the older onset asthma is still unclear. In this study, we investi-gated the conditions of Dermatophagoides farinae (Df )-induced asthma models by dividing mice according to age. Methods: Group of mice (C57BL/6, male) at the age of 6 weeks, 6 months, 1 year, and one-and-a-half years old were used to develop the asthma model. The mice were chal-lenged with 5 µg of Df intra-nasally, twice a week for 3 weeks. Twenty-four hours after the last Df challenge, bronchoalveolar lavage fluid (BALF)and lung tissue were collected. The BALF were analyzed for total and differential cell counts and measurement of cytokines production. TheLung tissues were stained with H&E, PAS, α-SMA, and Masson’s trichrome stain and analyzed for thickness of airway smooth muscle, goblet cellmetaplasia, and lung fibrosis. Results: The number of total cells and eosinophils in BALF were significantly increased in Df -induced asthma modelusing 6 weeks old mice compared to control group. The number of total cells and eosinophils were decreased by about half in Df -induced asthmamodel using either 6 months old mice or 1-year old mice compared to 6 weeks old mice. Furthermore by using one-and-a-half years old mice forthe asthma model, almost none of the eosinophil was observed in the BALF. From the histological analysis, there was also similar trends in thick-ness of smooth muscle and goblet cell metaplasia. Conclusions: The present study show that the airway inflammation was reduced when themice used for asthma model was older. Especially, the eosinophilic airway inflammation hardly occurred when the mice were between 1 year andone-and-a-half years old. From these results, we expect that even older patients who develop asthma may have predisposing factor for asthma de-velopment at an early age.

PE8-14 Angiotensin-converting enzyme 2 (ACE2) activator attenuates house dust mite-induced allergic inflammation in mice

Asami Fukuda, Shuichiro Maruoka, Shiho Yamada, Yusuke Kurosawa, Yutaka Kozu, Yasuhiro Gon (Division of Respiratory Medicine, Depart-ment of Internal Medicine, Nihon University School of Medicine, Japan)

Background: House dust mite (HDM) is a natural allergen and related to the onset of bronchial asthma. Angiotensin-converting enzyme 2 (ACE2)is one of the ACE family molecules regulating a renin-angiotensin system. ACE2 has an anti-inflammatory activity to involved in innate immunityof inflammatory lung diseases, including pulmonary fibrosis, acute lung injury, acute respiratory distress syndrome, pulmonary hypertension(PH), asthma, and chronic obstructive pulmonary disease. However, little is known about the role of ACE2 in HDM-induced allergic airway inflam-mation. Here we hypothesized that intraperitoneal administration of ACE2 activator, diminazene aceturate (DIZE) might attenuate HDM-inducedallergic airway inflammation in mice. Methods: C57BL/6J mice were intratracheally exposed to HDM or phosphate-buffered saline (PBS) as con-trol on days 0, 7, and 14. We collected bronchoalveolar lavage fluid (BALF) and lung tissues on day 17 to evaluate eosinophilia and T-helper type 2cytokines in the BALF, airway inflammation and mucus hyperproduction in the lung tissues after HDM exposure. We also measured the airwayhyperresponsiveness to the bronchoconstrictor methacholine on day 17. We next administered intraperitoneally DIZE or vehicle on days 10 to 16during HDM sensitized and challenged phase. Then we measured eosinophilia and T-helper type 2 cytokines in the BALF, airway inflammationand mucus hyperproduction in the lung tissues and airway hyperresponsiveness on day 17. Results: Administration of DIZE reduced HDM-induced airway eosinophilia when compared with vehicle-treated mice. This was accompanied by a reduction in IL-5 and IL-13 concentration inthe BALF, and IL-13 and CCL20 concentration in the Lung, while by a rise in IL-10 concentration in the BALF. And Tissue histology showed thatDIZE treatment decreased the peribronchovascular infiltrates and goblet cell hyperplasia. Finally, DIZE suppressed the airway hyperresponsive-ness to the bronchoconstrictor methacholine when compared with vehicle-treated mice. Conclusion: These results suggest that ACE2 might beinvolved in HDM-induced asthma-like phenotypes in the airway of mice. ACE2 may represent a new therapeutic target for asthma.

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PE8-15 Inhibition of IL-23 attenuates airway hyperresponsiveness and inflammation in a murinemodel of neutrophilic asthma

Satoru Senoo1), Akihiko Taniguchi1), Junko Itano1), Lili Guo2), Naohiro Oda1), Akihiko Yoshimura3), Katsuyuki Kiura1), Yoshinobu Maeda1),Nobuaki Miyahara1,3) (Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medi-cine, Dentistry, and Pharmaceutical Sciences, Japan1); Department of Medical Technology, Okayama University Graduate School of Health Sci-ences, Japan2); Department of Microbiology and Immunology, Keio University School of Medicine, Japan3))

Rationale: Neutrophilic asthma is one of the phenotypes of asthma which is characterized by severe disease and steroid resistance. IL-17A is rele-vant to the pathophysiology of neutrophilic asthma, inducing neutrophilic inflammation and airway hyperresponsiveness. Because IL-23 is a proin-flammatory cytokine that induces production of IL-17A, it may play an important role in neutrophilic asthma. In this study, we determined therole of IL-23 in a murine model of neutrophilic asthma. Methods: C57BL/6 mice were intra-tracheally administered ovalbumin (OVA) withlipopolysaccharide (LPS) or phosphate buffered saline (PBS) only on day 0 and 6 for sensitization. The mice were challenged by inhalation expo-sure to aerosols with OVA on day 13. Anti-IL-23p40 antibody or control rat IgG was administered after OVA nebulization. On day 15, airway hy-perresponsiveness (AHR) was assessed by measuring changes in lung resistance in response to increasing doses of inhaled methacholine. Afterassessing AHR, the lungs were lavaged, and BAL fluid was assessed. The lungs were fixed by 10% formalin and evaluated histologically. Results:Sensitization with OVA/LPS and airway challenge with nebulized OVA induced increased neutrophil numbers in BAL fluid and higher AHR,compared to sham-sensitized mice. The asthmatic mice treated with anti-IL-23p40 antibody had lower AHR compared to the mice treated withcontrol antibody. Conclusions: These data suggest that IL-23 plays an important role for the development of neutrophilic asthma, and that con-trolling IL-23 is a promising therapeutic strategy for neutrophilic asthma.

PE8-16 Conventional type 2 lung dendritic cells in asthma mouse model significantly induce follicular helper T cells than conventionaltype 1

Shogo Sakurai1), Kazuki Furuhashi1,2), Ryo Horiguchi3), Masato Karayama1), Yuzo Suzuki1), Hironao Hozumi1), Noriyuki Enomoto1),Tomoyuki Fujisawa1), Yutaro Nakamura1), Naoki Inui1), Takafumi Suda1) (Second Division, Department of Internal Medicine, Hamamatsu Univer-sity School of Medicine, Japan1); Department of Laboratory Medicine, Hamamatsu University School of Medicine, Japan2); Advanced Research Fa-cilities and Services, Hamamatsu University School of Medicine, Japan3))

Rationale: Follicular helper T cells (Tfh) presents one of CD4+ T cell subtypes in lymphoid follicles and contributes to antibody production. Re-cently, Tfh has been reported an important role in the asthmatic immune response. However, it is not clear how to be induced Tfh differentiationin asthmatic lungs. On the other hand, dendritic cells have CD4+ T cell differentiation ability, especially two subtypes of lung dendritic cells(LDC), conventional type 1 (cDC1; XCR1＋CD172a－DC) and type 2 (cDC2; XCR1－CD172a＋DC), differentially induce distinct CD4+ T cell sub-types. But, it is unknown which LDC subtype induces Tfh differentiation in asthmatic lungs. We examined functional difference in inducing Tfhdifferentiation between cDC1 and cDC2, and assessed specific immunoglobulins eliciting by Tfh in asthma mouse models.Methods:We observedTfh and two LDC subtypes in C57BL/6 mice immunized ovalbumin (OVA). cDC1 and cDC2 were highly purified from enzymatically digested sen-sitized lungs of OVA asthma mouse model by MoFlo Astrios cell sorter. The isolated cDC1 and cDC2 were co-cultured with nave OT-II CD4+ Tcells in the presence of OVA peptide for 7days. The cultured CD4+ T cells and supernatant were collected and analyzed Tfh differentiation. In ad-dition, Tfh were isolated from mediastinal lymph nodes (MLN) of OVA asthma model, and co-cultured with nave germinal center B cells (GCB) inthe presence of OVA for 7days. The supernatants were collected, and measured specific immunoglobulin levels by ELISA. Results: Numbers ofTfh in MLN and LDC increased in OVA asthma model. Percentages of cDC2 mainly increased day 7 after sensitization. CD4+ T cells co-culturedwith cDC2 significantly induced percentages of Tfh than those with cDC1 (3.9±1.1 vs 0.8±0.2%, p<0.05). Tfh from MLN of OVA asthma modelelicited OVA specific IgG1 (53.2±9.2 ng/mL) and IgE (62.0±27.3 pg/mL) in supernatants co-cultured with GCB. Conclusions: These data suggestthat cDC2 preferentially induced Tfh and asthmatic immune response compared to cDC1.

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PosterSession

Poster Session 9Atopic dermatitis 1

PE9-1 Long-term outcomes of 0.1% tacrolimus eye drop in eyes with severe allergic conjunctival diseases

Hiroyuki Yazu1,2), Kazumi Fukagawa2,3), Eisuke Shimizu2), Hiroshi Fujishima1,2,3) (Department of Ophthalmology, Tsurumi University School of Den-tal Medicine, Japan1); Department of Ophthalmology, Keio University School of Medicine, Japan2); Ryogoku Eye Clinic, Japan3))

Purpose: To evaluate of long-term results of 0.1% tacrolimus eye drops in the treatment of severe allergic conjunctival diseases. DESIGN: Retro-spective, observational study.Methods: Two hundred and seventy eyes of 135 patients diagnosed with atopic keratoconjunctivitis (AKC) or ver-nal keratoconjunctivitis (VKC) from April 2004 to April 2014 were screened, and finally 24 eyes of 12 patients who were treated with 0.1%tacrolimus eye drops were studied. Severity of objective signs and intraocular pressure (IOP) were observed at baseline, after 2 weeks, 1, 2, 3, 6,and 12 months, and every 1 year thereafter (average use period; 101.0±34.4 months). Ten objective signs for the palpebral and bulbar conjunc-tiva, limbus, and cornea were assessed. Safety was assessed based on the severity and the incidence of adverse events. Results: The total score ofthe clinical signs significantly decreased after 2 weeks and remained effective thereafter. Treatment was gradually tapered, with increasing inter-vals between applications. Tacrolimus eye drops elicited a statistically significant difference in the mean total clinical scores and IOP over thetime course of treatment (<0.001). 6 eyes were mainly aggravated by spring or poor compliance. Elevated IOP was observed in 4 eyes and cornealinfection in 1 eye, which were controlled completely with medical treatment. Conclusion: The results of this study suggest that topical tacrolimusmay effectively and lengthy improve clinical signs of severe AKC and VKC cases refractory to standard conventional treatment.

PE9-2 Successful topical treatment with ketoconazole for facial rashes refractory to dupilumab in patients with atopic dermatitis

Naoko Okiyama1), Ken Igawa2) (Department of Dermatology, University of Tsukuba, Japan1); Department of Dermtology, Dokkyo Medical Univer-sity School of Medicine, Japan2))

Dupilumab is a human monoclonal antibody blocking the signalling pathways of interleukin (IL)-4 and IL-13 to treat patients with moderate-to-severe atopic dermatitis (AD). Some AD patients develop refractory facial erythematous lesions, which may be an adverse effect of topical corti-costeroids. A report based on data from three phase III clinical trials indicated that dupilumab improved AD across different anatomical regions,however, resulted in inferior improvements for the head/neck. Here, we report four AD male cases with facial rashes refractory to dupilumabtreatment, which were successfully treated with topical ketoconazole. Case 1 (26 year-old), Case 2 (35 year-old), Case 3 (47 year-old) and Case 4 (46year-old) presented with severe AD since their childhood. Their Eczema Area and Severity Index (EASI) for the head/neck and EASI for thebody excluding head/neck were 3.75 - 4.75 and 20.4 - 22.5, respectively. They were treated with dupilumab (300 mg biweekly after a loading doseof 600 mg subcutaneously). AD significantly improved in their bodies and extremities after 9 - 10 months of dupilumab treatments, however, theirfacial rash did not improve despite combination therapy with mild-class topical corticosteroids and tacrolimus ointment. Physical examinations re-vealed erythema on the forehead, eyebrows, nasolabial folds, cheeks, and lower jaw excluding areas around the eyes. Due to discrepancy in theimprovement between the face and the rest of the body, and the distribution of the facial rash, a seborrheic dermatitis-like condition was consid-ered in each case. Additional topical treatment with a ketoconazole cream (twice daily) to dupilumab treatments improved EASI for the head/neck, which were closer to those in the body and extremities after a 2-month treatment with ketoconazole cream. In conclusion, topical ketocona-zole should be considered as an additional treatment option for AD patients with a seborrheic dermatitis-like facial rash that is refractory to dupi-lumab treatment.

PE9-3 Dupilumab treatment for atopic dermatitis leading to unexpected development of arthritis and enthesitis with increased serum IL-6: a case report

Takuya Nakazawa1), Hidekazu Futami1), Yoshihiro Oya1), Kazuyuki Ishijima1), Keiko Umemiya1), Emiko Tanabe2), Ryutarou Matsumura1) (Depart-ment of Rheumatology, Allergy & Clinical Immunology, National Hospital Organization Chibahigashi National Hospital, Japan1); Department ofDermatology, Asahicho Clinic, Japan2))

Background: Dupilumab, a fully human monoclonal antibody that blocks (interleukin) IL-4 and IL-13 signaling, is the first biologic for refractoryatopic dermatitis(AD). Despite the counter-regulatory relationship between Th1 and Th2 cytokines, cumulative cohort studying the comorbidityof Th2 mediated diseases such as asthma or AD, and Th1/Th17 mediated diseases such as rheumatoid arthritis (RA) did not come to a unanimousconclusion. Here we report a case of AD, who developed arthritis after the administration of Dupilumab. Case Report: A 59-year-old male withadult-onset severe AD having used topical steroid for 12 years began dupilumab to alleviate skin atrophy, side effect of steroid. On dupilumab, hisatopic condition improved remarkably, but 8 weeks later, pitting edema of bilateral ankle, and arthralgia of hand, elbow and shoulder were devel-oped. He had no history of joint disease, but his mother had RA. His renal function was normal but blood examination revealed a slight increase ofC-reactive protein (CRP) 0.37mg/dl and ESR 12mm/hr. Ultrasonography examination revealed mild active enthesitis of bilateral achilles tendonsand synovitis of fingers and shoulders. Mild collections of Gallium67 were observed in bilateral shoulders and knees. Although rheumatoid factor(RF) and anti-CCP antibody were both negative, serum IL-6 was elevated to 5.0pg/mL (reference value <4.0pg/mL). Prednisolone(15mg) wasstarted for the arthritis and enthesitis, which rapidly improved in a week with stable AD. Serum IL-6 level was also reduced to 1.0pg/mL a monthafter the cessation of dupilumab. Discussion: Our case developed arthritis and enthesitis, with elevated serum IL-6 following the blockade of Th2cytokines by dupilumab. To date, adverse events (AEs) of arthritis/joint pain described on phase III studies of dupilumab, was equivalent to pla-cebo group, whereas three cases of arthritis/enthesitis, occurring after dupilumab initiation was reported in the literature. Although cumulativecohort analysis of comorbidity of AD and RA did not come to a unanimous conclusion, comorbidity of AD and arthritis in these cases might be areplication of counter-regulartory relationships between arthritis related cytokines and Th2 cytokines in a clinical setting.

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PosterSession

PE9-4 The contribution of L-type amino acid transporter 1 in activated Th2 cells for the development of atopic dermatitis

Osamu Kaminuma1,3,5), Keitaro Hayashi2), Tomoe Nishimura3), Mayumi Saeki3), Takachika Hiroi3), Yohei Iwata4), Kazumitsu Sugiura4), Akio Mori3,5)(Department of Disease Model, Hiroshima University, Japan1); Department of Pharmacology and Toxicology, Dokkyo Medical University School ofMedicine, Japan2); Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Japan3); Department of Dermatology, FujitaHealth University School of Medicine, Japan4); Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Japan5))

Background: The role of L-type amino acid transporter 1 (LAT1) in the development of atopic dermatitis (AD) was investigated.Methods: Immu-nohistochemical analysis was performed to analyze the expression of LAT1 on CD4+ T cells in the skin of the patients with AD. The contributionof LAT1 to antigen-induced skin inflammation was examined by employing antigen-specific Th2 cell-transferred mice and a LAT1-specific inhibi-tor. LAT1-mediated cellular events in human and mouse T cells were investigated in vitro. Results: LAT1 expression was strongly augmented onskin-accumulated CD4+ T cells of AD patients. Obvious inflammatory responses in the skin associated with eosinophil accumulation, Th2 cytokineexpression and increased serum IgE were developed in ovalbumin-specific Th2 cell-transferred mice upon antigen challenge. Antigen-inducedskin inflammation in not only immunized mice but also Th2-transferred mice was significantly suppressed by the treatment with the LAT1 inhibi-tor. LAT1-mediated amino acid starving responses including glycolysis, oxidative phosphorylation, and activating transcription factor 4-drivenChaC glutathione specific gamma-glutamylcyclotransferase 1 expression were crucial for activation-induced cytokine production and proliferationof Th2 cells. Conclusion: Activated Th2 cells play a crucial role in the pathogenesis of AD through LAT1-dependent mechanisms. The possiblemanagement of AD patients by targeting LAT1 is suggested.

PE9-5 Differences of duration of effect of each moisturizer to dry skin surface

Katsuhito Iikura (Department of Pediatrics, National Hospital Organization Nishisaitama Chuo National Hospital, Japan)

Introduction: Moisturizer is usually prescribed many kinds of skin disorder in children such as atopic dermatitis and dry skin. However, thereare many moisturizers, effective time after application to skin of those are not clearly. In this study we sought to determine the effective times ofeach moisturizer by using skin impedance method.Methods: Four volunteer subjects with dry skin were enrolled in this study. Water content ofskin surface which was applied moisturizers was analyzed by impedance sensor (Mobile Moisture HP10-N) at pre-application, 30min, 1h, 3h, and 6h. Six moisturizers were used in this study (Hirudoid Lotion (HL), Hirudoid Soft Ointment (HSO), Vaseline, Nivea Cream (Nivea), Heparinoid fromanimal organs (HF), HSO-Vaseline Mixture). Effectiveness of each moisturizer was evaluated by the change rate of impedance values from base-line and those were compared among used moisturizers. Results: Water contents were increased after all moisturizer compared to control areawhich was not applied no moisturizer. At 30min, change rate of impedance showed maximum value, HF (58.7%), Vaseline (46.9%), Nivea (46.3%),HSO (46.2%), HSO-Vaseline Mixture (46.0%), and HL (43.4%) and following gradually decreased. At 6h, change rate of impedances of HF (46.4%),HSO (35.7%), and HL (31.5%) were higher compared to those of HSO-Vaseline-Mixture (26.2%), Vaseline (20.3%), and Nivea (16.2%). Conclusions: Ef-fectiveness of moisturizer was evaluated by skin impedance methods. At 6 h later, moisturizers continuously maintained the water contents of ap-plied area. HF, HSO, and HL were kept its effect 6 hours, but Vaseline and Nivea were weak in its continuous effect. Additionally, in the case ofmixing the moisturizers with each others, its effect might be diminished.

PE9-6 The effect of hospitalization on a year-long prognosis of moderate to severe atopic dermatitis

Masataka Suehiro, Akio Tanaka, Michihiro Hide (Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima Uni-versity, Japan)

Background: Hospitalization is recommended for patients with moderate to severe atopic dermatitis (AD), especially when they are chronic, se-vere and have not responded to standard therapies or when nonadherence is suspected as a cause of treatment failure. Hospitalization may do of-fer an opportunity of adequate and sufficient amount of education to the patients and their families, and assess the patient’s understanding and ac-ceptance of the treatment plan. However, little has been investigated about the effects of hospitalization on the course of AD, especially after thedischarge. In this study, we investigated retrospectively whether hospitalization has an impact on the clinical course of AD over a year.Methods:The data was extracted from the medical information of 86 patients with AD who first visited the Department of Dermatology, Hiroshima Univer-sity Hospital from January to December 2018. We investigated EASI scores of the patients at the first consultation, changes of serum TARC lev-els, the status of consultation, and complications that occurred over a year. We compared data of the patients who were hospitalized, patients whowere recommended to do but not actually admitted, and patients who were not recommended hospitalization. Results: Out of 86 cases, 23 patientswere recommended hospitalization by dermatologists, and 14 patients, 8 men and 6 women, with a mean age of 32.9 years, were admitted. Pa-tients who did not accept hospitalization were higher in the proportion of men, EASI score and serum TARC levels at the first consultation thanthose who accepted hospitalization. Serum TARC levels decreased rapidly in a few months in both groups, but the proportion of patients main-taining reduced TARC levels was higher in the patients who accepted hospitalization. Complications of acne, folliculitis, and dyshidrotic eczemaduring treatment were more common among the patients who were recommended hospitalization than the patients who were not. Conclusion:Hospitalization may be more effective in maintaining remission for a year. Women were more tolerant toward hospitalization, regardless of thedisease severity.

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PosterSession

PE9-7 Efficacy and fastness of antigen specific intradermal immunotherapy using Maximum Intradermally Tolerated Dose (MITD) in pa-tients with refractory atopic dermatitis

Kyoko S Nishikage1,2), Takeharu Yamanaka2) (Yokohama Nishikage Clinic: kids and Allergies, Japan1); Department of Biostatistics, School of Medi-cine, Yokohama City University, Japan2))

Background: The efficacy of antigen specific immunotherapies (e.g., subcutaneous injections) on atopic dermatitis has been controversial. We de-veloped an intradermal immunotherapy using MITD that seems to be more effective and fast-acting. We report on two cases who responded tothe therapy.Methods: First, patients’ offending antigens were confirmed, and antihistamine drugs were suspended for skin testing. Second, eachantigen’s MITD was found: 1. performed skin prick test (SPT) of the series of 5-fold dilutions of each antigen’s extract; 2. started intradermal test-ing with 0.05 ml of a weaker dose of the former examined SPT threshold; by giving progressively weaker doses, a certain dose terminated theslight systemic and skin reactions that had been induced. That was the treatment dose, MITD. Third, MITD was injected intradermally twice aweek for 6 months, and once a week thereafter. We have assessed the efficacy with patient questionnaires, doctor’s evaluation sheets, and somebiomarkers. We also evaluated accuracy of MITD with the results of basophil activation test (BAT) on the MITD concentration. Results: BetweenApril 2019 and March 2020, intradermal immunotherapy using MITD was administered to 2 patients from the single medical center; median age,42 (range, 36-48), 1 male. The phenotypes of the dermatitis were lichenified eczema for the male, and prurigo nodularis for the female. The causa-tive antigens were dust mites, candida, and yeast for the male, and Japanese cedar pollen and dust mites for the female. Both patients startedshowing favorable results in the first three months. There were over 70% improvements in Eczema Area and Severity Index and DermatologicalLife Quality Index for both patients. Thymus and activation-related chemokine levels showed a large decrease in the male patient, from 6025 to252, and a moderate one in the female, 689 to 560. Levels of s-IgE showed moderate reductions in most of the antigens. In BAT, basophils lost theiractivation on MITD concentrations. Conclusion: Antigen specific intradermal immunotherapy using MITD was effective and fast-acting to treatrefractory atopic dermatitis.

PE9-8 The plasma miR223 level might be a useful diagnostic biomarker for severe atopic dermatitis

Risa Tamagawa-Mineoka, Risa Yasuike, Naomi Nakamura, Koji Masuda, Norito Katoh (Department of Dermatology, Graduate School of MedicalScience, Kyoto Prefectural University of Medicine, Japan)

Background: MicroRNAs (miRNAs) are small non-coding RNAs, containing 1925 nucleotides, which bind to specific mRNAs to regulate theirtranslation or accelerate mRNA degradation. miRNAs have been identified not only in cells, but also in bodily fluids, such as plasma, serum, andurine. It is considered that the miRNAs in bodily fluids might be useful as non-invasive biomarkers for detecting disease. It was recently reportedthat close relationships exist between miRNAs and allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis (AD).Methods: A totalof 21 adult AD patients (10 males, 11 females; median age: 43 years old, range: 2262 years old) were randomly selected and registered for thisstudy. Ten patients with urticaria (2 males, 8 females; median age: 38.5 years old; range: 2361 years old) were randomly selected and registered forthis study. The control group was 13 healthy volunteers (5 males, 8 females; median age: 36 years old; range: 2254 years old) who had not takenany medication for at least 2 weeks. miRNAs were detected in the subjects’ plasma samples using specifically primed RT-PCR. Results: Based onthe eczema area and severity index (EASI) score, the 21 AD patients were divided into 3 groups: the mild (7 patients; score: <10), moderate (7 pa-tients; score: 1020), and severe (7 patients; score: >20) groups. The plasma miR223 levels of the severe AD patients were significantly higher thanthose of the mild AD patients, urticaria patients, and healthy controls. In addition, the plasma miR223 levels of the AD patients were positivelycorrelated with their serum TARC levels, but not with their blood eosinophil counts, serum IgE levels, or serum LDH levels. Conclusion: Ourfindings demonstrate that miR223 is significantly associated with the mechanisms underlying worsening AD, and indicate that the plasma miR223level might be a useful diagnostic biomarker for severe AD.

PE9-9 High-throughput screening for potent inhibitor of Staphylococcus aureus derived from atopic dermatitis

Tomofumi Numata, Kazumasa Iwamoto, Ryu Miyake, Michihiro Hide (Department of Dermatology, Graduate School of Biomedical & Health Sci-ences, Hiroshima University, Japan)

Background: S. aureus derived from atopic dermatitis (AD strains) compared with standard strains of S. aureus (standard strains) were selec-tively internalized into the lysosomes of keratinocytes, and induced Th2-immune responses via Langerhans cells. We explored inhibitors otherthan disinfectants or antimicrobials to block the internalization of AD strains. Methods:We cultured HaCat cells at 96-well plates overnight, andadded 1453 reagents, which are clinically available drugs, to each well. After cultured at 37 ℃ for 24 hours, we added heat-killed AD strains andstandard strains. After the stimulation of S. aureus for 22 hours, two immunostaining methods were performed; direct stain of S. aureus byfluorescent-labeled S. aureus antibody (S. aureus Antibody method) or via lysosomes in HaCat cells by using Cell Navigator ™ Lysosome stainingKit (Lysosome method). We calculated fluorescein isothiocyanate (FITC) spots per 100 HaCat cells treated with 1453 reagents by a high-throughput screening system. Results: In the first screening, 1453 reagents were tested at 2 µM and narrowed down to 70 reagents based on thehighest inhibition rate (IR;={1 FITC spots per 100 cells/FITC spots per 100 cells (positive control)} x 100 (%)). They consisted of 50 reagentsscreened by the Lysosome method (IR>31.3%) and 20 reagents by the S. aureus Antibody method (IR>56.2%). The ratio of cell death was 3.85%and the range of whole IR was -158.6% to 90.3%. Then, we performed two rounds of the second screening for the 70 reagents at 2 to 10 µM by theLysosome method. Finally, we classified reagents into 12 pharmaceutical groups. Conclusion: We found 59 potential reagents against AD strainby using the high-throughput screening system. Further study is in process to establish the optimal concentration of the reagents for their bio-logical activities against alive AD strains, and to elucidate the mechanism of such actions.

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PE9-10 Critical windows of air pollution exposure during pregnancy on offspring’s atopic dermatitis: COCOA study

Song-I Yang1), Hae Ran Lee1), Hyo-Bin Kim2), So-Yeon Lee3), Hwan-Cheol Kim4), Min Ji Park3), Hyeon-Jong Yang5), Kangmo Ahn6), Kyung Won Kim7),Youn Ho Shin8), Dong In Suh9), Soo-Jong Hong3) (Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College ofMedicine, Republic of Korea1); Department of Pediatrics, Inje University Sanggye Paik Hospital, Republic of Korea2); Department of Pediatrics,Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, Republic of Korea3); Department of Occupational and Envi-ronmental Medicine, Inha University School of Medicine, Republic of Korea4); Department of Pediatrics, Soonchunhyang University School ofMedicine, Republic of Korea5); Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Ko-rea6); Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Republic of Korea7); Department of Pediat-rics, CHA Gangnam Medical Center, CHA University School of Medicine, Republic of Korea8); Department of Pediatrics, Seoul National UniversityCollege of Medicine, Republic of Korea9))

Background: Prenatal period is considered as critical period for the effects of air pollution exposure on the development of allergic diseases. Littleis known regarding the critical windows of air pollution exposure during pregnancy on offspring’s AD. The aim of our study was to determine thecritical windows during pregnancy for the effects of air pollution in relation to offspring’s AD. Methods: Mother-child pairs were enrolled fromCOCOA birth cohort. PM2.5, PM10 and NO2 were estimated by land-use regression models. AD diagnosis was based on parental report of a phy-sician’s diagnosis. We applied a Bayesian distributed lag interaction model to identify critical windows during pregnancy for the effects of prena-tal air pollution in relation to offspring’s AD. Results: During 1-9 weeks and 1-4 weeks of gestation were critical windows for the effect of PM2.5and PM10 on AD at 1year of age, respectively. NO2 exposure during pregnancy did not increase the risk of AD at 1 year of age. PM2.5 exposureduring 1-9 weeks of gestation still increased AD at 1year of age after adjusting for PM10 and NO2. However, PM10 during pregnancy did not in-crease the risk of AD at 1 year of age after adjusting for PM2.5 and NO2. Conclusion: Higher PM2.5 during 1-9 weeks of gestation affect off-spring’s AD after adjusting for the effects of other air pollutants. Avoidance of PM2.5 exposure from the early pregnancy may prevent offspring’sAD.

PE9-11 Gut linoleic acid is associated with the severity of atopic dermatitis and sensitization to egg white/milk in infants

So-Yeon Lee1), Yoon Mee Park2,3), Hyun Ju Yoo4), Dong In Suh5), Youn Ho Shin6), Kyung Won Kim7), Kangmo Ahn8), Soo-Jong Hong2) (Department ofPediatrics, Asan Medical Center, Republic of Korea1); Department of Pediatrics, Childhood Asthma and Atopy Center, Republic of Korea2); AsanInstitute for Life Sciences, University of Ulsan College of Medicine, Republic of Korea3); Department of Convergence Medicine, Asan Institute forLife Sciences, Asan Medical Center, University of Ulsan College of Medicine, Republic of Korea4); Department of Pediatrics, Seoul National Univer-sity College of Medicine, Republic of Korea5); Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Re-public of Korea6); Department of Pediatrics, Yonsei University College of Medicine, Republic of Korea7); Department of Pediatrics, Samsung Medi-cal Center, Sungkyunkwan University School of Medicine, Republic of Korea8))

Background: Serum linoleic acid has been shown to exert anti-allergic and anti-inflammatory effect on atopic dermatitis. However, the relation-ship between gut linoleic acid and atopic dermatitis remains unknown. Objective: We investigated whether gut linoleic acid in six-month-old in-fants could be associated with the severity of atopic dermatitis and sensitization to egg whites or milk. Methods: We analyzed the non-targetedmetabolomic profiles of gut metabolites by using fecal samples from 39 healthy infants, 10 infants with mild atopic dermatitis, and 22 infants withmoderate to severe atopic dermatitis. The Scoring Atopic Dermatitis index was calculated in infants at six months of age and serum IgE specificfor milk and egg white was measured at 12 months of age. Results: Linoleic acid metabolism in the gut varied according to the severity of atopicdermatitis. The levels of gut linoleic acid and 13-oxo-octadecadienoic acid were significantly reduced in the moderate to severe atopic dermatitisgroup compared with the healthy control and mild atopic dermatitis groups (P<0.05). Gut linoleic acid negatively correlated with Scoring AtopicDermatitis and IgE specific for egg or milk (P<0.05). Conclusion: Gut linoleic acid may be associated with the severity of atopic dermatitis andsensitization to egg white or milk during infancy.

PE9-12 Moderate-intensity aerobic exercise reduces allergic inflammation in a mouse model of atopic dermatitis

Young Yoo1,2), Wonsuck Yoon1), Dasarang Kim1), Jaehoon Lim1), In Soon Kang1), Hyo Sun Lee1), Seunghyun Kim1), Dae Jin Song1,2) (Allergy Immunol-ogy Center, Korea University, Republic of Korea1); Department of Pediatrics, Korea University College of Medicine, Republic of Korea2))

Background: Earlier reports have indicated that aerobic exercise improves the overall physical fitness and health in patients with atopic dermati-tis (AD). However, the mechanisms underlying the benefits of aerobic exercise in AD are not well understood. The aim of this study was to inves-tigate effects of accumulated and continuous aerobic exercise activities in modulating inflammatory responses associated with AD in a mousemodel. Methods: Mice were treated with DNCB to develop dermatitis symptoms, similar to patients with AD at the age of 7 weeks. The micewere randomly assigned to one of the following 3 groups: (1) those which were treated with DNCB and not subjected to aerobic exercise (CNgroup, n=6), (2) those which were treated with DNCB and subjected to accumulated aerobic exercise (AA group, n=6) and (3) those which weretreated with DNCB and subjected to continuous aerobic exercise (CA group, n=6). The exercise was given using a treadmill device for 30 min/day at a speed of 16 m/min for 9 days. Results: Dermatitis symptoms were ameliorated in the AA and CA groups compared to the CN group.There were no significant differences in dermatitis scores between the AA and CA groups. The thickness of epidermis/dermis was reduced, andimmunocyte infiltration was decreased in the AA and CA groups compared to the CN group. The serum levels of IgE, MCP-1, and TSLP weresignificantly reduced in the AA and CA groups compared to the CN group. However, the serum levels of MDC and IL-31 showed a significant de-crease in the AA group, but not in the CA or CN groups. Conclusions: Moderate-intensity aerobic exercise decreased dermatitis symptoms, cy-tokine production and eosinophil infiltration in the DNCB-treated AD-like mouse model. The results of this study suggest that moderate-intensityaerobic exercise can be used as an alternative therapy in AD.

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PosterSession

PE9-13 Role of toxocariasis in formation and course of atopic dermatitis

Revaz Sepiashvili1), Sopio Gamkrelidze2), Manana Chikhladze2,3), Darejan Khachapuridze2,3) (Peopels Friendsip University of Russia, Russian Fed-eration1); National Institute of Allergology, Asthma and Clinical Immunology, Georgian Academy of Sciences, Georgia2); Akaki Tsereteli State Uni-versity, Faculty of Medicine, Georgia3))

We studies of the patients with atopic dermatitis.. The results of the studies revealed a high percentage of helminthiasis among the etiological fac-tors of atopic dermatitis. Aim of the Study:Monitoring the patients with atopic dermatitis caused by toxocariasis and evaluation of the clinical ef-fects of the course of targeted treatment. 33 patients (16 women and 17 boys), 12 to 75 years of age, with toxocariasis, atopic dermatitis of variousseverity of the clinical course were involved in the study. The monitoring diagnostic program in these patients included :total IgE test measuringIgE level in the blood serum to determine the allergenization degree; serological immunoenzymatic tests on helminths: toxocari, ascarid, lamblia;.Analysis of the obtained results showed that the total IgE level was higher than the norm in 86% of 33 patients examined, an average index - 400se/ml ; diagnosis of helminths revealed epidemically high frequency and high correlation with allergenization degree on toxocara in all 33 pa-tients. Ascariasis was diagnosed in 6 and lamblia in 2 patients, respectively; a high degree of correlation between toxocariasis titer and high levelsof total IgE and, consequently, severe clinical course of the disease was observed as well. Treatment included a 10-day course of albendazole ther-apy repeated at 3 week-interval. In parallel, the patients used long-term antihistamine therapy. Monitoring of patients showed the need to repeatthe treatment of toxocariasis - 2-3 full course at 6-month intervals, in parallel with the monitoring of blood glucose (blood sugar) levels. A high cor-relation between the clinic of atopic dermatitis and high titer of toxocara in the blood was also confirmed. The clinical effect was achieved only af-ter the level of toxocara in the blood returned to the norm. This study indicates to the necessity of producing epidemiological statistics onhelminths, consequently, applying targeted strategic preventive measures undoubtedly will determine the reliable clinical outcomes at atopic der-matitis. The publication has been prepared with the support of the“RUDN University Program 5-100”.

PE9-14 Epidemiologic alpeculiarities of allergic dermatitis in children and adolescents in the population of Georgia

Revaz Sepiashvili1), Darejan Khachapuridze2,3), Manana Chikhladze2,3), Nino Adamia4), Maya Maglaperidze1) (Peopels Friendship University of Rus-sia, Russian Federation1); National Institute of Allergology, Asthma and Clinical Immunology, Georgian Academy of Sciences, Georgia2); AkakiTsereteli State University, faculty of Medicine, Georgia3); Tbilisi State Medical University, Georgia4))

The aim of our study was an investigation of epidemiological peculiarities of allergic dermatitis in children and adolescents in the population ofGeorgia. The study group included 2699 children, from 3 months to 15 years of age (girls - 1721 and boys - 978) living in Kutaisi, Tbilisi and Batumi.On the first stage of study, the survey was completed by direct with the parents. The clinical verification of diagnosis was carried according toISAAC. The studied three groups: the first group - from 3 months to 3 years of age, the second group -to 9 years and the third group 9 - 15 years.During 24 months the episodes of recurrent itching was revealed in 12.9% of studied population, 39.7% of which consisted of the second group,11.6% -first age-group, 48.7%-to the third age-group. The rate of distribution of the symptoms of allergic dermatitis was relatively higher amongthe boys in comparison with the girls (P<0.05) In 5.8% of cases, these symptoms were accompanied with various skin inflammatory diseases whichwere identified in 9.8% of the population. Atopic dermatitis was diagnosed in 24.8% of cases; urticaria- 5.9%; angioedema- 2.4% of the studied popu-lation; contact dermatitis in 2.9%; seborrheic dermatitis 3.2%; psoriasis - in 1.8% (P<0.05). Late and hypo-diagnosis of allergic dermatitis remains aproblem. By skin prick-tests, the prevalence (61.2% P<0,05) of food allergy and sensitization (21.0% P<0.05) of allergic eosinophilic esophagitis inadult population have been confirmed. IgE proved to be high in 79% of patients. The allergen-specific IgE antibodies should be always found inblood serum. Approximately 79% of patients have high blood serum IgE levels and peripheral blood eosinophilia (P<0.05). The allergen- specificblood serum IgE-antibodies will be always detected, as it was proved by our study. The current study requires paying more attention to the pro-spective monitoring of the mentioned groups of the child population and studying the peculiarities of the further manifestations of allergic atopicdermatitis. The publication has been prepared with the support of the“RUDN University Program 5-100”.

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PosterSession

Poster Session 10Atopic dermatitis 2

PE10-1 A case of iatrogenic cushing’s syndrome due to corticosteroid and antihistamine combination therapy for pediatric atopic derma-titis

Mai Yokoyama, Norio Kawamoto, Chisa Kumagai, Saori Kadowaki, Tomohiro Hori, Takahiro Yamamoto, Kazuo Kubota, Takeshi Kimura,Minako Kawamoto, Hidenori Ohnishi (Department of Pediatrics, Graduate School of Medicine, Gifu University, Japan)

Background: The primary treatment for atopic dermatitis is topical corticosteroids; however, administration of systemic corticosteroids maycause adverse effects. We report a case of Cushing’s syndrome caused by corticosteroid and anti-histamine administration in a child. Case: A 9-year-old girl with short stature was referred to our hospital. She had been suffering from atopic dermatitis since she was 2 years old, and she in-termittently took a betamethasone (0.25 mg) and dextrochlorpheniramine (2 mg) combination tablet for 18 months because of the insufficient ef-fect of topical corticosteroid therapy. Physical examination revealed a moon face and a buffalo hump, presence of papules on the cubital fossa andwrists, lichenification and melanosis on the forehead, neck, trunk, and lower legs, which was not well controlled. Her Eczema Area and SeverityIndex (EASI) score was 19.5. Blood test results showed normal thyroid function and a low cortisol level. Her height was 116.8 cm (-2.45 standarddeviation), and her weight was 31.5 kg; the body mass index was calculated to be at the 97.1 percentile for her age and sex. Her growth started toslow down at 8 years of age. After systemic corticosteroid discontinuation, her endocrinological assessment suggested adrenocortical insuffi-ciency. Therefore, she was diagnosed with iatrogenic Cushing’s syndrome. Because she had a risk of adrenal crisis, she began taking a physiologi-cal dose (10 mg per day) of hydrocortisone replacement therapy. Atopic dermatitis improved with appropriate skin care and ointment application,and then the EASI score declined to 5.4 in 2 weeks. Hydrocortisone therapy was decreased gradually over four months and then discontinued.Moreover, her growth velocity had improved. Her skin condition was well maintained after she started appropriate skin care. Conclusion: Thiscase suggests the importance of skin care and topical therapy and reveals the risk of adrenocortical insufficiency with continuous oral corticoster-oid therapy, especially for children in the growth period.

PE10-2 Close association of dog exposure and the exacerbation in two cases of atopic dermatitis with dog allergy

Kanako Ogura, Haruhi Yamada, Ayaka Ariyoshi (Department of Dermatology, Kobe City Hospital Organization Kobe City Medical Center WestHospital, Japan)

Background: There is few evidence that dogs increase the risk of atopic dermatitis (AD) in contrast to cat epithelia exposure. Here, we reporttwo cases of AD that were suspected to have deteriorated disease associated with sustained contact to their domestic dogs. Case 1: A 2-year-oldboy had been diagnosed with AD at 6 months of age, which continued to worsen rapidly after the age of 2 years. He had been in contact with hisfamily pet dog since birth. Laboratory evaluations were as follows: TARC>30,000 pg/ml, total IgE 4530 IU/mL, sIgE to Dermatophagoides ptero-nyssinus : 0.39 UA/mL, to cedar: 0.6 UA/mL, to cat epithelia: 0.79 UA/mL, to dog dander: 89.9 UA/mL, to egg white: 19.6 UA/mL, and to ovomucoid:4.27 UA/mL. Inpatient treatment was followed by the removal of the dog from the home, which improved his AD. Case 2: A 29-year-old man pre-sented to our hospital for treatment with dupilumab to improve his eczema. His symptoms had undergone remission during the overseas stay forbusiness, and worsened upon return. He had kept a dog at home for 5 years. Laboratory evaluations were as follows: TARC 11,895 pg/ml, totalIgE 2524 IU/mL, sIgE to D. pteronyssinus : 9.79 UA/mL, to cedar: 8.59 UA/mL, to cat epithelia: 6.7 UA/mL, to dog dander: 97.3 UA/mL, to candida :4.02 UA/mL, and to pityrosporium : 4.90 UA/mL. He separated his living environment from the dog in parallel with starting dupilumab treatment.His symptoms rapidly improved and he has maintained good control since. His dog dander sIgE level was significantly reduced compared withother allergens. Conclusion: Dog allergen exposure by keeping a dog indoors may have close association with the exacerbation of AD with dog al-lergy. The identification of individual trigger factors is crucial for the management of AD.

PE10-3 Dietary habits in adult Japanese patients with atopic dermatitis

Naoko Kanda1), Michiko Ito2), Takashi Morita1), Shizuka Okazaki1), Mototaka Koto1), Yuri Ichikawa1), Ryoko Takayama2), Toshihiko Hoashi2),Hidehisa Saeki2) (Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Japan1); Department of Dermatology, Nippon Medi-cal School, Japan2))

Background: Atopic dermatitis (AD) is a chronic eczematous disease characterized by abnormal immune responses skewed to Th2-phenotype,pruritis, and skin barrier impairment. Dietary habits can modulate the pathogenesis of AD. We evaluated these habits in adult Japanese AD pa-tients.Methods: Seventy adult AD patients (43 men and 27 women) answered a validated, brief-type self-administered diet history questionnaire,and the intakes of energy, food items, and nutrients were calculated based on the answers. The results of the patients were compared to those ofage- and sex-matched healthy controls, using Wilcoxon signed rank tests. The AD patients were divided into the severe group (severity scoring ofatopic dermatitis [SCORAD] ≧ 33) and mild group (SCORAD<33), and the differences between the groups were analyzed by Mann-Whitney Utests. The correlations between SCORAD and each variable were evaluated, using Spearman’s rho correlation coefficients. Results: Patients withAD showed higher intakes of carbohydrate and potatoes and lower intakes of alcohol, niacin, meat and oils/fats compared to those of the healthycontrols. The results of logistic regression analysis, adjusted for age, sex, and body mass index, showed that the intake of alcohol was negativelyassociated with AD (odds ratio 0.905; 95% confidence interval 0.832 - 0.983; p=0.0181). The intakes of vitamin B6 and fruit were positively corre-lated with SCORAD. Multiple regression analysis, adjusted for age, sex, and body mass index, revealed that vitamin B6 intake was a predictor ofSCORAD (β=26.98508709, t=2.3995292, p=0.01933781). The intakes of vegetable fat, n-6 polyunsaturated fatty acid, and confections were lower inthe severe AD group than those in the mild group. Conclusion: AD is negatively associated with alcohol intake, and intake of vitamin B6 is a pre-dictor of SCORAD. The intake of n-6 polyunsaturated fatty acid is lower in the severe AD group than that in the mild group. Further study iswarranted on the relationships of these results with abnormal immune responses, impaired skin barrier, or pruritus in AD.

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PosterSession

PE10-4 A survey of clinical practice of atopic dermatitis for dermatologists in Japan

Sakae Kaneko1), Takeshi Nakahara2), Hiroyuki Murota3), Akio Tanaka4), Yoko Kataoka5), Takeyasu Kakamu6), Norito Kato7) (Department of Derma-tology, Shimane University Faculty of Medicine, Japan1); Division of Skin Surface Sensing, Department of Dermatology, Graduate School of Medi-cal Sciences, Kyushu University, Japan2); Department of Dermatology, Nagasaki University Graduate School of Medicine, Japan3); Department ofDermatology, Graduate school of Biomedical & Health Sciences, Hiroshima University, Japan4); Department of Dermatology, Osaka HabikinoMedical Center, Japan5); Department of Hygiene & Preventive Medicine, Fukushima Medical University School of Medicin, Japan6); Departmentof Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan7))

Atopic dermatitis (AD) is treated by various strategies based on the experience of doctors, the needs of patients, and the motivations of patientsto treat each other. The actual condition of medical care was investigated for the purpose of“Improving skills in AD treatment”in the AD specialsubcommittee of Japanese Society for Cutaneous Immunology and Allergy. From October 2019 to January 2020, 284 responses were received andthe response rate was 22.5%. Cronbach’s alpha was 0.78 after removal of data with obvious errors, to ensure internal validity. Although 18 prob-lems in AD treatment were listed and divided into 3 groups according to the degree of problems, no significant differences were found in affili-ation, age, presence or absence of specialists, etc., and the percentage of patients who answered“recovering from AD”,“be satisfied with thetreatment of”, or“Prospects and disease states of the treatment are explained.”was significantly higher in the group without difficulties in medi-cal care. Those who had criteria for discontinuing proactive therapy were younger, more likely to be allergic specialists, and more likely to readthe guidelines and refer to them in their practice. These results suggest that the goals of treating patients with AD as an incurable disease are dif-ferent from those described above, and that the feeling of difficulty in treatment may increase. Therefore, support for such groups of physicians isnecessary.

PE10-5 Dupilumab induces eight categories of facial responses in atopic dermatitis: a long-term, single-center, observational study

Yoko Kataoka, Rai Fujimoto, Sachiko Sakamoto, Ayaki Shigyo, Hirohiko Shirai, Eiji Kawasaki (Department of Dermatology, Osaka Habikino Medi-cal Center, Japan)

Background: Dupilumab is well-known to improve symptoms in moderate-to-severe atopic dermatitis patients. However, dupilumab leads toslow facial lesion improvement and occasional development of new facial lesions that prompts physicians to judge whether dupilumab should bediscontinued or combined with other treatments. Methods: Clinical changes in the facial lesions of 65 moderate-to-severe adult atopic dermatitispatients (male:female, 58:7) who had been receiving dupilumab for over one year at our department were retrospectively analyzed. Facial Investi-gator’s global assessment (F-IGA) score was graded by a physician. Dermoscopic photographs were taken by DermliteDL3 every 4 months. Biop-sies were taken for some typical cases. Total EASI score, POEM, DLQI, and blood biomarkers including peripheral eosinophils, LDH, TARC, andtotal IgE were recorded simultaneously. Results: F-IGA scores of 0, 1, 2, 3, and 4 changed from 3%, 21%, 13%, 41%, and 22% to 30%, 27%, 7%, 27%,and 0%, respectively, after one year. Changes in facial lesion were categorized into eight types: 1. no lesion ever since (9%); 2. rapidly disappearing(14%); 3. gradually improving (25%); 4. persistent flushing with dermoscopic telangiectasia (26%); 5. persistent refractory facial lesion requiring ad-ditional medication (8%); 6. newly developed rosacea-like dermatosis, red face (12%); 7. exfoliative erythema due to abrupt cessation of topicalmedication (6%); and 8. complication with contact dermatitis (1%). Histologically, type 5 showed sebaceous gland hyperplasia with follicular spongi-osis with lymphocytic infiltration with some eosinophils. Type 6 showed marked vasodilatation of the upper dermis with perivascular lympho-cytic infiltration. Systemic metronidazole was useful to relieve this dermatosis. Dermoscopically, type 4 showed telangiectasia that often increasedin degree with continuous administration of dupilumab, but decreased with prolonged dupilumab interval after remission of extra-facial lesionswas achieved. Conclusions: The pathogenesis and clinical features of adult facial lesion of atopic dermatitis are complex. Facial responses to dupi-lumab varied in each pathogenesis. Recognition of each category, additional treatment with or without topical or systemic medication, and adjust-ment of dupilumab frequency were needed for higher patient satisfaction and successful treatment outcome.

PE10-6 Dupilumab for a girl with severe asthma, atopic dermatitis, and school refusal

Satoshi Yamada1), Yutaka Nishida1), Shun Takahashi1), Naoya Arakawa1), Toru Uchida1), Koichiro Sato2), Satomi Hagiwara1,3), Hisako Yagi1),Hirokazu Arakawa1), Takumi Takizawa1) (Department of Pediatrics, Gunma University Graduate School of Medicine, Japan1); Department of Pedi-atrics, Takasaki General Medical Center, Japan2); Shigeta Child Allergy Clinic, Japan3))

We used dupilumab, an antibody against interleukin-4 receptor α, for a child who had not attended school owing to severe asthma and atopic der-matitis (AD). A 13-year-old girl, who developed atopic asthma at the age of six, sensitized to multiple inhalant allergens antigens, required exerciserestriction even with a salmeterol/fluticasone combination (50/100 µg twice daily) therapy. She also had severe AD with dry and inflamed skinwith generalized lichenification; the AD brought her appearance-related bullying at school. This, in addition to her and her family’s mental prob-lems, caused her school refusal. Hence, she was hospitalized after starting dupilumab. Two weeks later, the rash and itchiness had started improv-ing. Two months later, SCORAD, serum total IgE level, and TARC improved from 69.8 to 10.3, 7641 to 228 IU/mL, and 2454 to 247 pg/mL, respec-tively. Dmin with AstographⓇ increased from 0.304 to 1.531 units, and the fraction of exhaled nitric oxide decreased from 44.0 to 17.5 ppb, suggest-ing that airway hyperresponsiveness and inflammation had been ameliorated. She resumed school because she was less anxious about her ap-pearance because of the improvement in her skin symptoms. Exercise restrictions were also reduced. Dupilumab improved not only the physicalillness but also likely promoted psychological and social development by fostering self-efficacy and improving quality of life; hence, starting treat-ment during childhood is important.

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PosterSession

PE10-7 Continued treatment with dupilumab (LIBERTY AD OLE) provides clinical benefits in most adults with moderate-to-severeatopic dermatitis not achieving optimal response to short-term treatment

Joo Young Roh1), Young Lip Park2), Chun Wook Park3), Zhen Chen4), Arima Kazuhiko5), Oh EunSil6), Brad Shumel4), Ana B Rossi7) (Gachon Univer-sity, Gil Medical Center, Republic of Korea1); Soonchunhyang University, College of Medicine, Republic of Korea2); Hallym University, College ofMedicine, Republic of Korea3); Regeneron Pharmaceuticals, Inc., USA4); Sanofi K.K., Japan5); Sanofi-aventis, Republic of Korea6); Sanofi Genzyme,USA7))

Background: Previous data have suggested that continued treatment with dupilumab may benefit patients with moderate-to-severe atopic der-matitis (AD) who do not optimally respond to initial short-term treatment (Deleuran M, et al. 2020). Here, we report dupilumab efficacy up toWeek 100 in an open-label extension (OLE) study (LIBERTY AD OLE, NCT01949311) in adults with moderate-to-severe AD who did not have aclinically relevant improvement in either AD signs, symptoms, or quality of life at the end of their parent study.Methods: LIBERTY AD OLE en-rolled adult patients (18 years) with moderate-to-severe AD who had previously participated in a dupilumab clinical study. All patients receiveddupilumab 300 mg weekly, and long-term safety and efficacy were assessed. This analysis was performed on a subset of patients treated withdupilumab in the parent study and who did not achieve a 50% improvement from baseline in Eczema Area and Severity Index (EASI-50), or aver-age Pruritus Numerical Rating Scale (PNRS) score <4, or Dermatology Life Quality Index (DLQI) <6 at the end of the parent study, and had as-sessments for all these endpoints at Week 100 in the OLE study. Results: Of 918 adult OLE patients who had been treated with dupilumab intheir parent study and had not achieved EASI-50 or had PNRS score 4 or with DLQI score 6 at the end of their parent study, assessments for all 3endpoints at Week 100 were available for 226 patients. At Week 100 of OLE, 224 of 226 (99.1%) achieved either EASI-50, or PNRS <4, or DLQI <6.Dupilumab was well tolerated, and safety data were consistent with the known dupilumab safety profile. Conclusion: Continued long-term treat-ment with dupilumab (up to 100 weeks) in patients with moderate-to-severe AD provides clinically relevant improvements in AD signs, symp-toms, or quality of life in almost all patients who did not optimally respond to short-term treatment, regardless of the dosage received in the par-ent study.

PE10-8 Difference between the characteristics of inpatients with skincare for Atopic Dermatitis (AD) in 2009 and 2018 in our department

Yoko Murakami1), Masaaki Kawano1), Daisuke Yasunari1), Takeshi Oki1), Koki Okabe1), Kento Fukushima1), Mihoko Iwata1), Masatoshi Wakatsuki1),Naohiko Taba1), Hiroshi Matsuzaki1), Chikako Motomura1), Satoshi Honjyo1,2), Akiko Sugiyama1,2), Hiroshi Odajima1) (Department of Pediatrics, Na-tional Hospital Organization Fukuoka Nartional Hospital, Japan1); Department of Dermatology, National Hospital Organization Fukuoka NationalHospital, Japan2))

Background:We made an inpatient skincare educational program (basically 2 nights 3 days) for children with AD in 2009 and reported its effec-tiveness (Murakami Y, JJACI 2017). Aim: To identify of the characteristics of AD children with recent hospitalization.Method: The subjects wereinpatients for skin care. We compared clinical characteristics of group 1 (previous report; August 2009 to June 2011, n=49) with those of group 2(January 2018 to December 2019, n=82). Results: Patients in group 2 than group 1 had a higher average age (2y0m vs 7y8m), longer duration ofAD (19.6 vs 82.2m), more receiving skincare education before hospitalization (28.6 vs 61.0%), longer hospital stays (4.2 vs 4.8 days), less complica-tions with food allergy (85.0 vs 51.2%) and lower mean Eczema Area and Severity Index (EASI) at admission (27.8 vs. 17.3). EASI was reduced dur-ing admission in both groups. Discussion: The group 2 patients were older and more poorly controlled. It may be, thus, speculated that youngerpatents are fairly controlled with the improved recent skincare at outpatient clinic. Conclusion: A characteristic of AD patients requiring recenthospitalization was that of school-age children with poorly controlled.

PE10-9 The case series study for the specific phenotypes of atopic dermatitis with rapid response to the treatment with dupilumab

Rai Fujimoto, Hidefumi Kawasaki, Sachiko Sakamoto, Ayaki Shigyo, Hirohiko Shirai, Yoko Kataoka (Department of Dermatology, Osaka HabikinoMedical Center, Japan)

Background: In the treatment with dupilumab for atopic dermatitis, some patients show rapid disappearance of symptoms, then they have beenmaintaining remission with less topical corticosteroids on a long-term basis. Seeking these high responders is beneficial to select the most appro-priate patients for dupilumab treatment who have high possibility of the best cost-effective long-term control by further reduced minimum dos-age. It is presumed that such patients have common clinical appearances of atopic dermatitis. Method: 125 patients of atopic dermatitis treatedwith dupilumab from April 2018 to October 2019 were included. Patients, who have achieved IGA 0 or1 at 16weeks and have been maintaining re-mission more than a year without additional anti-inflammatory treatments, were defined as a“rapid responder”group for dupilumab. Thechanges in EASI score, serum TARC levels, and serum IgE levels were compared with other patient groups. The changes in POEM scores wereassessed for stratification in phenotypes of atopic dermatitis. Then, the clinical characteristics of each patient in the rapid responder group werereviewed. Results: 13 patients were classified for the good responder group. Though serum IgE levels were significantly decreased in the com-parison of other patients, there were no significant differences in the changes in EASI score and serum TARC levels. For the clinical characteris-tics, isomorphic nodules or edematous erythema with severe scalp eczema were featured in the rapid responder group. Conclusion: Patients clas-sified as the rapid responder group have specific phenotypes. Precise classification of phenotypes could make it easy to carry out precision medi-cine in the treatment of atopic dermatitis.

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PosterSession

PE10-10 Different preferences between patients and physicians for the treatment of atopic dermatitis in Japan

Yukari Okubo1), Kerrie-Anne Ho2), Simon Fifer2), Hiroyuki Fujita3), Yasuyo Oki3), Yurie Taguchi3) (Department of Dermatology, Tokyo Medical Uni-versity, Japan1); Community and Patient Preference Research Pty Ltd (CaPPRe), Australia2); Sanofi K.K., Japan3))

Background: Emollients and both topical and systemic anti-inflammatory agents are traditional treatment options for atopic dermatitis (AD).More recently, a new biologic has been approved as an additional option. However, it is unclear whether or how patients and physicians differ intheir preferences for treatment because of paucity of research.Methods: A discrete choice experiment methodology was used to quantify patientand physician preferences for treatment. Participants were presented with a series of choice scenarios where they were asked to choose theirpreferred treatment options that were described using the following attributes: add-on or replacement treatment, efficacy of improving rashesand itching, time until response, place of administration, injection site reaction, risk of mild to moderate and severe side effects, frequency of ad-ministration and cost. Participants completed the study via an online survey. Results: 76.7% of physicians and 46.2% of patients opted-in to thenew treatment in the scenarios presented. There were also differences in the treatment preferences among the patients and physicians whoopted-in to treatment. Physicians were more likely to value the efficacy of the treatments in treating rashes and were more concerned about thecost of treatment than patients. In contrast, patients preferred an add-on treatment and were against self-administering the treatment at home.Conclusion: Overall, there are differences between patients and physicians in their preferences for AD treatments. These findings have implica-tions for shared decision-making and treatment discussions in clinical practice and subsequently better treatment outcomes.

PE10-11 A real-world treatment landscape of atopic dermatitis in Japan

Kazumasa Kamei1), Hidehisa Saeki2), Takanori Tsuchiya1), Tomohiro Hirose1), Eduardo Kawasaki1), Fumihiro Matsumoto1), Noritoshi Yoshii1),Shinichi Imafuku3) (Pfizer Japan Inc., Japan1); Department of Dermatology, Nippon Medical School, Japan2); Dermatology, Fukuoka University, Ja-pan3))

Background: This study is aimed to assess how therapeutic approaches for atopic dermatitis (AD) have been changing with the course of time,and how medical facilities differ on the selection of AD-related treatment. Methods: The JMDC (Tokyo, Japan) claims database was analyzed inthis study. Patients with AD were defined as patients who had at least once confirmed diagnosis based on ICD10 code between January 2005 andDecember 2018, an identifiable medical care start date for AD after January 2005 and at least twice prescription claims of AD-related treatmentson separate dates. The number of patients and population ratio in total were compiled and analyzed in each year by gender, age, medical facilities,laboratory tests, AD-related treatments and medical expenses. Results: In total, 406,840 subjects were qualified for this analysis. Gender ratio wasapproximately 1:1 in each year, but the median age increased year after year. Dermatologists and clinics were the main specialty and medical fa-cility, respectively, for AD-related treatment prescriptions in any period. There were no significant differences in the proportion of patients whoreceived antihistamine/antiallergic agent, and weak to strong topical corticosteroid (TCS) in each year. On the other hand, the proportion of pa-tients who received thymus and activation-regulated chemokine (TARC) test, moisturizer, topical calcineurin inhibitor (TCI), very strong tostrongest TCS, cyclosporine, phototherapy and AD-related medical expenses increased with the course of time. In 2017, 49.5% patients receivedvery strong to strongest TCS or systemic treatments at least once a year. Interestingly, the ratio of patients who received weak to very strongTCS was higher in clinics, and for those who received strongest TCS, TCI and systemic treatments was higher in university hospitals than inother type of facilities. In regard to medical specialists, dermatologists prescribed more TCS and TCI than pediatricians, internal medicine doctorsor others including allergists. Conclusion: Highly effective treatments tended to be selected and prescribed to patients over the course of time,and in addition, AD therapeutic approaches might differ from medical facilities.

PE10-12 Dupilmab is effective for the treatment of intractable prurigo in adult atopic dermatitis

Satoshi Takeuchi, Mari Kiyomatsu-Oda (Department of Dermatology, Federation of National Public Service Personnel Mutual Aid Associations,Hamanomachi Hospital, Japan)

Background: Atopic dermatitis (AD) with prurigo are very refractory and use of the existing effective treatment such as systemic cyclosporinecould be difficult depending on the patients conditions (renal insufficiency, cancer-bearing, specific medication such as statins). Thus the purposeof the study was to examine the clinical effects of Dupilmab for the treatment of AD with prurigo. Methods: Dupilmab was administered for 20adult patients with intractable atopic dermatitis (AD) (mean age: 44.4y, male/female=16/4, illness period: 30.1y, NRS-itch: 7.1, EASI: 36.9, BSA: 74.5,IGA: 3.90, TARC: 2469 pg/ml, total IgE: 8160 IU/ml, eosinophil counts: 804/µl), and its clinical effects were compared between AD with prurigo (n=13) and those without (n=7) using mean % reduction from the baseline values. Results: NRS-itch (prurigo: -59.2%, non-prurigo -72.5%), EASI (-49.3%, -68.7%), TARC (-68.8%, -88.2%), total IgE (-33.9%, -32.3%) were significantly (p=0.05) reduced from the baseline in both clinical types at 2months after the start of administration, but the degree of % reduction of EASI and TARC were significantly lower in AD with prurigo comparedto those without. Conclusion: Dupilmab was effective for the treatment of intractable nodular prurigo in AD, but the relief speed of diseases se-verity appeared slower in AD with prurigo than those without.

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PosterSession

PE10-13 Increased incidence of conjunctivitis with dupilumab treatment in adolescents appears to be specific to atopic dermatitis

Marjolein De Bruin-Weller1), Eric L Simpson2), Amy S Paller3), Elaine C Siegfried4,5), Jonathan Corren6), Zhen Chen7), Ana B Rossi8),Kazuhiko Arima9), Faisal A Khokhar7), Ashish Bansal7) (University Medical Center, The Netherlands1); Oregon Health & Science University, USA2);Northwestern University Feinberg School of Medicine, USA3); Saint Louis University, USA4); Cardinal Glennon Children’s Hospital, USA5); DavidGeffen School of Medicine at UCLA, USA6); Regeneron Pharmaceuticals, Inc., USA7); Sanofi Genzyme, USA8); Sanofi K.K., Japan9))

Background: To report the incidence of conjunctivitis in adolescents treated with dupilumab or placebo in clinical trials for atopic dermatitis(AD) or asthma.Methods: Patients aged≧12 to <18 years received subcutaneous (SC) dupilumab 300mg every 4 weeks (q4w; n＝83), 200/300mgevery 2 weeks (q2w; n＝82), or placebo (n＝85) for 16 weeks for moderate-to-severe AD in the randomized, placebo-controlled LIBERTY ADADOL trial (NCT03054428); or add-on SC dupilumab 200mg q2w (n＝34), 300mg q2w (n＝34), or placebo (n＝39) for 52 weeks for uncontrolledmoderate-to-severe asthma in the randomized, placebo-controlled LIBERTY ASTHMA QUEST trial (NCT02414854). Conjunctivitis events (Med-DRA Preferred Terms: conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, adenoviral conjunctivitis, atopic kerato-conjunctivitis) during the treatment period were summarized. Results: The proportion of patients with ≧1 conjunctivitis event was 4.7%/10.3%in the placebo/combined dupilumab (300mg q4w or 200/300mg q2w) groups in the AD ADOL trial, and 2.6%/2.9% in the placebo/combined dupi-lumab (200mg or 300mg q2w) groups in the ASTHMA QUEST trial. 2.4%/7.9% of patients (placebo/combined dupilumab) in the AD ADOL trialhad ≧1 conjunctivitis event considered related to study drug; no events were considered related to study drug in the ASTHMA QUEST trial.Conjunctivitis cases in both trials were mostly mild or moderate in severity, most resolved during the treatment period, and none resulted in per-manent discontinuation of study treatment. Dupilumab demonstrated significant efficacy and acceptable safety vs placebo in the AD ADOL andASTHMA QUEST trials. Conclusion: A higher incidence of conjunctivitis was observed in adolescents treated with dupilumab than with placeboonly in the AD clinical trial, whereas the incidence of conjunctivitis in adolescents in the asthma clinical trial was low and similar between dupi-lumab and placebo. Similar results were reported in adults.

PE10-14 Oral immunosuppressants in pediatric patients with moderate or severe atopic dermatitis

Joaquin Pimentel1), Mirna Toledo2), Omar Saucedo1) (Department of Allergy and Immunology, Hospital Infantil de Mexico Federico Gomez (WAOCenter of Excellence), Mexico1); Department of Dermatology, Hospital Infantil de Mexico Federico Gomez, Mexico2))

Background: Atopic dermatitis can affect 20% of pediatric patients and 3% of adults. In pediatric patients with moderate or severe atopic derma-titis refractory to first and second-line treatment, there is no established scheme for oral immunosuppressants such as cyclosporine and azathio-prine, in addition, the evidence of the efficacy and safety of these drugs in pediatric patients with atopic dermatitis is scarce.Method: a retrospec-tive, single-center study was conducted, which included pediatric patients with moderate or severe atopic dermatitis according to the SCORADindex, refractory to first and second-line treatment and who had received treatment with cyclosporine or azathioprine for at least 4 weeks. Initialobjective SCORAD, at 4, 12, 24 weeks, and 12 months, adverse events and the percentage of patients who had a decrease ≧25% in objective SCO-RAD were reported. Results: A total of 44 patients were enrolled in the cyclosporine group, comparing the means of the objective SCORAD, astatistically significant reduction was obtained at 4 (p<0.000001), 12 (p<0.0001), 24 weeks (p<0.001) and at 12 months (p<0.0005) and 60% of the pa-tients reduced ≧25% the objective SCORAD at 4, 12, 24 weeks and 12 months. A total of 13 patients were enrolled in the azathioprine group, astatistically significant reduction in the objective SCORAD was obtained at 4 (p<0.01), 12 (p<0.009), 24 weeks (p<0.006) and 12 months (p<0.001)and 87.5% of the patients reduced ≧25% the objective SCORAD at 12 months. In the cyclosporine group, 33.3% of the patients reported adverseevents, but only one required drug suspension. In the azathioprine group, none of our patients presented myelosuppression or liver damage in thefirst 12 months of treatment. Conclusion: cyclosporine and azathioprine are effective options in pediatric patients with moderate or severe atopicdermatitis refractory to first and second-line treatment and where systemic steroid treatment was also not effective. Clinical trials are needed toverify these findings.

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PosterSession

Poster Session 11Case report: asthma and airway disease

PE11-1 A case of chronic cough caused by protracted bacterial bronchitis in a patient with long-term management of asthma

Rieko Higashijima1,2), Natsuko Masumoto2), Momoko Sakurai2), Junichiro Tezuka3) (Department of Pediatrics, Tagawa Municipal Hospital, Japan1);Department of Pediatrics, National Hospital Organization Fukuoka-Higashi Medical Center, Japan2); Department of Allergy and Pulmonology,Fukuoka Children’s Hospital, Japan3))

Background: Cough often occurs in children who have long-term management of bronchial asthma, and the causes are generally acute exacerba-tion of bronchial asthma, infection, and allergic rhinitis. We report a case of cough during the long-term management of bronchial asthma, whichwas difficult to diagnose. Case: An 11-year-old girl developed bronchial asthma at the age of 5 years and initiated long-term management. Omali-zumab was administered at the age of 7 years as the most severe persistent type, and the control was good thereafter. At 11 years of age, she de-veloped wet cough with purulent sputum. Acute exacerbation of bronchial asthma was suspected, short-term treatment was added, and theomalizumab dose was increased according to weight gain, but no improvement was achieved. The cough persisted for 3 months or more, and weconsidered infection, allergic rhinitis, sinusitis, foreign bodies, gastroesophageal reflux disease, and bronchiectasis as differential diagnoses for thechronic cough. Examination and treatment were performed, but they were not effective. The wet cough persisted for more than 4 weeks, and inthe sputum, eosinophils were not found, neutrophils were predominant, and Haemophilus influenzae was detected in sputum culture. Thus, pro-tracted bacterial bronchitis was diagnosed, and ampicillin was administered for 14 days, with continuation of low-dose clarithromycin, followingwhich she showed an improvement in the symptoms. Discussion: Protracted bacterial bronchitis is considered a common cause of chronic wetcough in infancy, but its frequency in Japan has not been clarified. Although this case involved a school-aged child, the persistent cough needed aconsideration of protracted bacterial bronchitis.

PE11-2 Exercised-induced laryngeal obstruction and low end-expiratory lung volume in an asthmatic adolescent

Tai Q Tran, Huyen TK Dang, Lan TT Le (Department of Respiratory Functional Exploration University Medical Center, Viet Nam)

Inducible laryngeal obstruction and dysfunctional breathing are differential diagnoses of asthma according to the GINA guideline. Cardiopulmon-ary exercise testing (CPET) is an advanced method that evaluates cardiovascular, respiratory, and neuromuscular systems simultaneously duringvigorous exercise. Flow measurement during CPET can provide further evidence of exercised-induced laryngeal obstruction (EILO) and abnor-mal breathing strategy. An 11-year-old male patient was diagnosed with asthma and allergic rhinitis 6 years ago. He has a history of recurrentbreathlessness, wheezing, productive cough, and sometimes cyanosis at night. Spirometry results over last year were normal. He was currentlyprescribed with fluticasone/salmeterol 25/125 mcg 2 puffs bid/day for his partly controlled asthma. Clinical examination showed enlarged tonsilsand no wheezing. CPET was conducted with cycle ergometer. The protocol was as followed: 3 min warming at 25W, increasing workload at 13W/min, and finally 2 min recovery at 25W. The duration of the patient’s test was 14 minutes in total. Maximal exercise criteria were fulfilled withmaximal heart rate at 88% predicted, respiratory exchange ratio at 1.29, and peak minute ventilation at 80% MVV. VO2peak was 1.15 L/min andspecific VO2peak was 27 mL/kg/ph. Ventilation threshold 1 is 27% as compared to VO2max predicted. Airflow measurement was recordedevery 2 minutes throughout the protocol and repeated when abnormal findings were observed in end-expiratory lung volume (EELV). At 2:15min, airflow curve was recorded moving to the right at residual volume level (low EELV) and expiratory airflow limitation was observed. At an in-creasing workload, tidal volume and flow surged consistently. Subsequently, at 07:36 min, fixed airway obstruction pattern was seen and becameclearly at peak exercise at 07:56 min. In the recovery stage, this pattern disappeared slowly with increasing EELV and became normal at the endof the test. This CPET results revealed evidence of EILO and breathing strategy at low EELV. These conditions can contribute to the respiratorysymptoms and partly controlled asthma of this patient, which need to be investigated in the future.

PE11-3 An asthmatic case of psoriasis vulgaris caused by administration of dupilumab

Hideyasu Yamada1,2), Takashi Matsuda1), Norihito Hida2), Nobuyuki Hizawa1) (Division of Respiratory Medicine, Faculty of Medicine, University ofTsukuba, Japan1); Division of Respiratory Medicine, Hitachi Ltd, Hitachinaka General Hospital, Japan2))

Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL-4 receptor alpha chain and inhibits type 2 inflammation. It is suitable foratopic dermatitis and asthma therapy. Some side effects reported to date are injection site reactions, conjunctivitis, and rarely anaphylaxis. Wepresent a patient with severe asthma who experienced the onset of psoriasis after treatment with dupilumab. A 60s male had been diagnosedwith asthma and treated with an inhalation therapy of inhaled corticosteroids (ICS), long-acting beta agonist (LABA), and long-acting muscarinicantagonist (LAMA) for 6 years at our hospital. Despite these treatments, his respiratory symptoms were not well controlled, and short-term sys-temic corticosteroid administration was often required. In May 20XX, he started dupilumab. Asthma symptoms and Th2-related inflammatoryparameters improved dramatically. However, by July, skin rashes on his knees and right condyle precipitated a dermatology visit at our hospitalfor the first time. These rashes, erythemic with keratinous proliferation and scales, were suspected as psoriasis and were treated with steroidcream. By August, his skin rashes had spread from his knees and right condyle to his hands, elbows, and face. We then stopped dupilumab. Theleft knee skin rash was biopsied in September where hyperkeratosis, thinning and disappearance of the stratum granulosum, and neutrophilic in-filtration into the stratum corneum were observed in the epidermal tissue. This led to a diagnosis of psoriasiform dermatitis. By September, onemonth after stopping dupilumab, the skin rashes were less visible and the scaling had decreased. We hypothesized that inhibition of IL-4/IL-13signaling by dupilumab may have stimulated the Th1 and Th17 differentiation that mechanistically promoted the psoriasiform dermatitis seen inour case. We report the first case of psoriatic eruption caused by the use of dupilumab in a patient with bronchial asthma, with some literatureconsiderations.

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PosterSession

PE11-4 Ultrasound “humidifier lung” caused by rare fungal pathogens identified in vitro: two case reports

Kai Ryu1,2), Kiyoshi Sekiya1), Akemi Saito1), Kentaro Watai1), Yosuke Kamide1), Yuma Fukutomi1), Takanori Numata2), Kazuyoshi Kuwano2),Katsunori Kamei3), Masami Taniguchi1,4) (Clinical Reserch Center for Allergy and Rheumatology National Hospital Organization Sagamihara Na-tional Hospital, Japan1); Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Japan2); My-cology Research Center, Chiba University, Japan3); Department of Allergy, Shonan Kamakura General Hospital, Japan4))

Background: Assays for detecting the presence of HP-causing pathogens in the domestic environment have been lacking. Case Reports: Case 1was a 72 year-old man with fever, dry cough, and shortness of breath admitted in our hospital. A chest radiograph (CXR) showed slight bilateralinterstitial infiltration in the upper segment, while a chest CT showed bilateral, patchy, ground-glass opacities and emphysema. We therefore per-formed provocation test for the humidifier in the hospital’s private room. The test results were positive based on Otani’s criteria of environmentalprovocation test. Therefore, we concluded the diagnosis to be hypersensitive pneumonitis without biopsy based on 4 items listed in Vasakova’scriteria for diagnosing humidifier lung. After humidifier use was avoided, no other external changes were required for improving the patient’scondition. We performed precipitation studies using humidifier water samples and the patient’s serum samples, and the result was positive forfungal pathogens. The causative pathogen was identified as a species belonging to the Fusarium oxysporum species complex. Case2 was a 61-year-old man diagnosed with abnormal lung opacities after performing thoracic CT. He was introduced to our hospital for suspected HP as he pre-sented persistent symptoms of dry cough, shortness of breath, and fever. Chest X-ray showed bilateral ground grass opacities in the upper lobes.Chest CT showed pale, grand grass opacities in the bilateral upper lobes. We repeated the provocation test in a private room in our hospital andthe results obtained correlated with the parameters considered in Otani’s criteria. After the patient avoided using the humidifier, no other envi-ronmental changes were required for improving the patient’s condition. Precipitating antibody reactions were positive for Aureobasidium pullu-lans based on the standard 30 antigens used for the assay. Identified the two causative microorganisms to be Purpureocillium illicium and Acre-monium sclerotigenum/egyptiacum. Conclusion:We reported two cases of humidifier lung wherein the following antigens were identified in nov-elty, through precipitating antibody test, using fungal antigens cultured from the humidifier water and the sera of the patients.

PE11-5 A case of refractory allergic bronchopulmonary aspergillosis successfully switched from mepolizumab to benralizumab

Chiyako Oshikata1,2), Takeshi Kaneko2), Naomi Tsurikisawa1,2) (Department of Allergy and Respirology, Hiratsuka City Hospital, Japan1); Depart-ment of Pulmonology, Yokohama City University Graduate School of Medicine, Japan2))

Introduction: Patients with allergic bronchopulmonary aspergillosis (ABPA) have frequent disease exacerbations (DE) owing Th2 hypersensitiv-ity to Aspergillus fumigatus colonization in bronchioles. Although these patients typically receive standard asthma treatment supplemented withsystemic corticosteroids and antifungal agents, this therapy fails to sufficiently control disease symptoms and DE in many patients. Therefore, animproved therapeutic strategy is needed. Case presentation: Our patient is a 47-year-old woman who has had unremitting, persistent, severeasthma since she was 2 years of age. At 26-year-old, she was diagnosed as ABPA according to Rosenberg’s criteria: history of asthma, peripheraleosinophilia, positive serum precipitation antibody reaction to Aspergillus , increased total serum-IgE, history of transient or fixed lung infiltratesand proximal bronchiectasis. Despite treatment with salmeterol-fluticasone propionate, a leukotriene receptor antagonist, and itraconazole over aperiod of 3 years, she continued to have chronic wheezing, bronchiectasis, and mucus-plugged bronchioles. She presented to our hospital at theage of 41-year-old. Consequently she received a short course of systemic corticosteroids, a second dose of fluticasone propionate was add to hertreatment regimen, and her antifungals was changed to voriconazole. In addition, she followed good allergen avoidance practices in her bedroom.However, because of her persistent, frequent DE over the next 2 years, she began receiving omalizumab monthly; nevertheless, she needed sys-temic corticosteroids eight times during the first year of this treatment, and her peripheral blood eosinophil count (Eos) was continuously high(maximum, 5050/µL). Consequently, after 26 months, omalizumab was discontinued, and she began to receive 100mg of mepolizumab monthly.During the first year of mepolizumab therapy, she had fewer DE (i.e., four), and Eos was decreased and stable (69-878/µL). However, after this firstyear, she experienced three DE in four months even though Eos did not increase (mean, 439.4µL[240-846/µL]). Therefore, mepolizumab was ex-changed for 30mg of benralizumab. During the first year of benralizumab therapy, she had only one DE with systemic corticosteroids, and herEos decreased markedly (mean, 29.6/µL[0-316/µL]). Conclusion: Benralizumab may be a good treatment option for severe ABPA.

PE11-6 A case of a patient with eosinophilic otitis media with progressing sensorineural hearing loss despite treatment with biologicalproducts

Wakako Nakanishi1), Michiko Uchiyama2), Wayo Kawawaki1), Hiroko Monobe1) (Department of Otolaryngology, Japanese Red Cross Medical Cen-ter, Japan1); Tokyo Metropolitan Police Hospital, Japan2))

Background: In recent years, it has become possible to use biological agents as therapeutics for severe bronchial asthma. As a result, suppressionof asthma attacks, reduction in emergency hospitalization and decreased steroid use have become possible. In addition, aspirin intolerance inbronchial asthma, eosinophilic sinusitis, and eosinophilic otitis media has also seen improvements in symptoms. However, we encountered onecase in which the progression of sensorineural hearing loss due to eosinophilic otitis media could not be suppressed even with various biologicaldrugs. Method: This is a case report of a 66-year-old woman who was diagnosed with severe aspirin-induced asthma at the age of 33 years. Shehas been treated in our respiratory internal medicine department since she was 52 years. At the age of 59 years, she was treated with omalizu-mab but used betamethasone frequently for asthma attacks. At the age of 62 years, mepolizumab treatment was initiated, but it was stopped dueto the development of rash. After that, she was treated with omalizumab and benralizumab, but she developed rashes again. At the age of 65years, she was treated with dupilumab. Her asthma symptoms improved but hearing loss progressed. Her pure tone hearing level reached Rt./Lt.=88.8/93.8 dB. We started treatments of dripping betamethasone. After that, her hearing level improved, and we gradually reduced the amount ofcorticosteroids. However, her hearing worsened again after the suspension of betamethasone. We reinitiated dripping betamethasone treatmentand continued low-dose oral steroids. Her hearing level maintained at Rt./Lt.=67.5/90.0 dB. Consideration: She was treated with several biologicalproducts, but bilateral sensorineural hearing loss progressed gradually. After the start of dupilumab, her asthma control improved, but a rapidprogression of sensorineural hearing loss was observed. As a result, she needed to take copious amounts of steroids. We experienced a difficultcase in maintaining hearing by long-term steroid administration. Even in healthy conditions of eosinophilic inflammation in the airway, differencesin drug sensitivity for each organ are widely considered to be involved.

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PosterSession

PE11-7 The effect of mepolizumab in asthmatic patients with chronic eosinophilic pneumonia

Haruna Sato, Hideki Inoue, Yoshito Miyata, Tetsuya Homma, Tomoki Uno, Yoshitaka Uchida, Hitomi Ida, Tomoyuki Kimura, Yousuke Fukuda,Megumi Jinno, Kuniaki Hirai, Shin Ohta, Mayumi Yamamoto, Yoshio Watanabe, Shintaro Suzuki, Akihiko Tanaka, Hironori Sagara (Showa Uni-versity School of Medicine, Department of Medicine, Division of Respiratory Medicine and Allergology, Japan)

Objective: IL-5 is a cytokine involved in eosinophilic inflammation. Mepolizumab, a humanized anti-IL-5 monoclonal antibody, has shown efficacyin asthma and eosinophilic granulomatosis with polyangiitis (EGPA). but until recently only some case reports are available and the treatmentconsensus of mepolizumab for asthmatic patients with CEP had not been well established. So we report five case series of a series of asthmaticswith corticosteroid-resistant CEP treated with mepolizumab and their steroid tapering effect in these patients and clinical trials.Methods:We ret-rospectively investigated medical records of our university hospital about the effectiveness of mepolizumab, especially in SC reduction effect, inasthmatic patients with CEP. We examined clinical data including age, sex, onset time of asthma and CEP, duration of illness, SC dose and dura-tion, comorbidities, reduction effect of SC, improvement of chest radiological findings, presence of complications, and side effects. Results:We re-viewed clinical data of 5 asthmatic patients with CEP who visited our university hospital from 2002 through 2019. Mean age among those patientswas 50.4±23.7 years old, and mean disease duration of CEP was 5.4±2.5 years. The means of peripheral blood eosinophil differentials and abso-lute numbers on the first mepolizumab administration were 16.5±7.2% and 3940±5827 cells/µl, respectively. Those after 1 month treatment ofmepolizumab were 0.98±0.68% and 66±48/µl, respectively. Mean serum total IgE before mepolizumab administration was 261±335 IU/mL. Themean of eosinophil differentials in bronchoalveolar lavage fluid among 4 patients who performed bronchoscopy was 45±32.8%. The mean steroiddosage of the initial and the time before mepolizumab treatment was 25±7.1 mg and 5.4±0.9 mg, respectively. All cases were successfullytreated by mepolizumab. None of patients experienced recurrence of CEP during mepolizumab treatment period albeit SC was being tapered.Conclusions: In asthma cases with CEP, mepolizumab showed steroid-sparing effect in all 5 cases at our university hospital. Considering less ad-verse event during mepolizumab treatment, mepolizumab could be an alternative treatment option for CEP patients, especially who receive long-term SC treatment.

PE11-8 A case of chronic hypersensitivity pneumonitis potentially due to past bird-raising and feather quilt use

Toshiyuki Kita1), Tomoyuki Araya1), Tamami Sakai1), Keigo Saeki2) (Respiratory Medicine, National Hospital Organization Kanazawa Medical Cen-ter, Japan1); Respiratory Medicine, Kanazawa University Hospital, Japan2))

Our patient was a 73-year-old woman with the chief complaints of dyspnea on exertion (mMRC 1) and a productive cough. She kept wild birds in-side her home from the age of 43 to 60 years. After renovating her home at the age of 61 years, she no longer kept any wild birds. The patient hadno smoking or dust exposure history. The patient had been aware of a productive cough for the previous year. She had dyspnea on exertion(mMRC 1) and weight loss (4 kg over 6 months) for the previous six months. On February 5, 2020, she presented to our department with a referral.She reported using a feather quilt. Her body temperature was 36.6℃, and SpO2 was 96% (room air). Fine crackles were heard on inspiration in thebilateral lungs on auscultation. Granular and patchy shadows were observed in the bilateral lung fields on a chest X-ray. Diffuse, centrilobulargranular shadows, reticular shadows, and ground-glass opacities were observed in the bilateral lungs on computed tomography. Lactate dehydro-genase (LDH) level was 266 IU/L, and Krebs von den Lungen 6 (KL-6) level was 8958 U/mL. The patient tested negative for anti-Trichosporonasahii monoclonal antibody and Mycobacterium tuberculosis interferon-γ. She also tested negative for all bird-specific antibodies, with a budgeri-gar immunoglobulin G (IgG) antibody level of 4.35 µg/mL, a pigeon IgG antibody level of 9.80 µg/mL, and a parrot IgG antibody level of 6.39 µg/mL. Cell count, lymphocyte proportion, and CD4/CD8 ratio in bronchoalveolar lavage fluid (right B5) were high at 4.4×105/mL, 91%, and 13.3, re-spectively. A granuloma was observed on a transbronchial lung biopsy (right B8). The patient was hospitalized and underwent two weeks of bedrest. Thereafter, the LDH, KL-6, and 6-minute walking test results (SpO2) slightly improved. The patient was diagnosed with chronic hypersensi-tivity pneumonitis based on her past history of bird-keeping and the use of a feather quilt. Oral prednisolone 20 mg/day was started, and thetreatment continues today.

PE11-9 A case of severe asthma controlled by dupilumab based on serum IL-4 levels

Takahiko Nakamura1), Soichiro Ikeda1), Sho Mitsuya1), Tomoya Funamoto1), Kiyoe Kanaoka1), Hiroyuki Tsuji1), Ninso Matsunaga1),Kenjiro Tsuruoka1), Shuhei Yoshida1), Yousuke Tamura1), Masafum Imanishi1), Yasuhito Fujisaka1), Akihisa Imagawa2) (Department of RespiratoryMedicine and Thoracic Oncology, Osaka Medical College Hospital, Japan1); Department of Internal Medicine, Osaka Medical College Hospital, Ja-pan2))

Case:Woman in 40s. Asthma Control Test (ACT) scored 6 points, indicating poor asthma control. Peripheral blood eosinophils count was 123/µL,serum IgE was 141 U/mL, and specific IgE against ticks, cedars, and hinoki were high. Fractioned exhaled nitric oxide (FeNO) was 13 ppb. Treat-ment: Her symptoms was not improved by treatment with high-dose inhaled corticosteroid, long-acting beta agonist, Long-acting muscarinic an-tagonists, and leukotriene receptor antagonist. We administered Omalizumab for 3 months, but her symptoms were poorly improved, and asthmaattacks requiring systemic steroid were often observed. As the levels of IL-4 was high but IL-5 was not elevated, we administered dupilumab. Bythe treatment of dupilumab, ACT improved to 15 points. Discussion: In this case, asthma symptoms were poorly controlled, but IgE, peripheralblood eosinophils, and FeNO, which indicate the presence of Type 2 inflammation, were low. Selection of antibody preparation based on the serumcytokine concentration was effective to control the patient’s asthma symptoms. In routine clinical practice, there are few opportunities to measureserum cytokines, but measuring IL-4 and IL-5 may enable to select the appropriate antibody preparation.

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PosterSession

PE11-10 Two cases of chronic eosinophilic pneumonia successfully long-term treated with benralizumab

Seiko Soeda, Ryuta Tsuzuki (Department of Allergy and Respiratory Medicine, The Fraternity Memorial Hospital, Japan)

Background: Chronic eosinophilic pneumonia (CEP) is an inflammatory disease characterized by eosinophilic infiltration in the lung. Once ex-pressed, many patients with CEP require systemic corticosteroids (SCSs). Long-term SCSs treatment can evoke adverse events such as weightgain, sleep disturbance, and infections. Therefore, safer and more effective agents are preferable for CEP treatment. Case:We report two cases ofCEP successfully long-term treated with benralizumab, which is a monoclonal antibody against the alpha submit of the IL-5 recepter. Case 1. Thepatient was a 71-year-old Japanese woman who visited our hospital with cough, fever, and abnormal chest radiograph findings. She had treatedwith ICS/LABA for her bronchial asthma (BA). Her laboratory data showed eosinophilia, and chest CT revealed infiltrative shadows. Bronchoal-veolar lavage fluid (BALF) included elevated eosinophils. We diagnosed CEP, and benralizumab was initiated for the treatment of the patient’sasthma with CEP because she refused SCSs use. After treatment with benralizumab, her symptom, laboratory data and radiograph findings ofCEP improved immediately. She received benralizumab treatment for 20 months and had no relapse of CEP. Case 2. The patient was a 77-year-oldJapanese woman who had been diagnosed as bronchial asthma 4 year earlier and CEP 2 year earlier. We diagnosed relapse of CEP because of theperipheral eosinophilia, elevated eosinophil percentages of BALF, and the infiltrative shadows on chest CT. SCSs and benralizumab were initiatedfor the treatment of CEP with BA. She received SCSs for only 2 weeks, because of her own experience of serious adverse events on CEP diagno-sis 2 years earlier. After treatment with benralizumab, her symptoms disappeared, and her peripheral eosinophil levels decreased. The abnormalshadows on chest CT disappeared after 3 months of the start of benralizumab treatment. She has experienced no relapse of CEP up to now withthe 18 months benralizumab treatment. Conclusion:We have reported two cases of CEP with successful long-term benralizumab treatment. Ben-ralizumab has fewer adverse effects than SCSs, so that it could be a widely accepted to treat CEP.

PE11-11 Acute eosinophilic pneumonia associated with COVID-19

Koji Kuronuma, Koutaro Murao, Atsushi Saito, Hirofumi Chiba (Department of Respiratory Medicine and Allergology, Sapporo Medical Univer-sity School of Medicine, Japan)

We report a case of acute eosinophilic pneumonia (AEP) triggered by COVID-19 infection. A 77-year-old man experienced left chest pain andshortness of breath. RT-PCR for SARS-CoV-2 was positive and he was treated with favipiravir, ciclesonide and lascufloxacin, but he had poor im-provement. On the other hand, CT Images were atypical for COVID-19 and blood tests showed the elevation of eosinophils. Although pathologicalexamination was not possible, we clinically diagnosed as AEP. The administration of prednisolone dramatically improved the clinical conditionand chest radiograph, which was consistent with the clinical course of AEP. This case suggested that it is necessary to consider complications ofAEP when treating patients of COVID-19.

PE11-12 A case of successful switching from omalizumab to mepolizumab for severe asthma with allergic bronchopulmonary mycosis

Kana Oshinden, Tsuyoshi Oguma, Naoki Okada, Shigeaki Hattori, Jun Tanaka, Asako Kitahara, Katsuyoshi Tomomatsu, Koichiro Asano (Divisionof Pulmonary Medicine, Tokai University School of Medicine, Japan)

Introduction: Our study of patients treated with an anti-IgE monoclonal antibody (omalizumab) for allergic bronchopulmonary mycosis (ABPM)with severe asthma in Japan showed that 80% of the cases presented with improved subjective symptoms, but improvement in radiographic im-aging were observed only in 54% cases. The clinical benefits of anti-IL-5 (or anti-IL-5 receptor) monoclonal antibody for ABPM have not been as-sessed in detail. Case: A 60-year-old female with a history of asthma and chronic rhinosinusitis with nasal polyps was referred for persistentcough, phlegm, and shortness of breath. She had been treated with inhaled corticosteroids for 13 years, but her respiratory symptoms were wors-ened 3 years ago, accompanied by peripheral blood eosinophilia and elevation of total serum IgE levels. A chest radiograph and a computed to-mography (CT) scan showed central bronchiectasis with high attenuated mucoid impaction. Laboratory data showed increased numbers of pe-ripheral blood eosinophils (574/L) and elevated total serum IgE (559 IU/mL). This case satisfied our new diagnostic criteria of ABPM. She wastreated with itraconazole and oral prednisolone, but the treatment was abandoned due to adverse effects. Intravenous Administration of omalizu-mab (600 mg every 4 weeks) was started. Although her symptoms were improved after the 16 week-treatment with omalizumab, FEV1 was de-creased from 1.56 to 1.24 L/second and mucoid impaction on chest CT was worsened. Although oral prednisolone improved her symptoms andchest CT findings, they deteriolated shortly after the reduction of oral prednisolone dose. An anti-IL-5 monoclonal antibody, mepolizumab (100 mgevery 4 weeks), was initiated. Mepolizumab improved respiratory symptoms, pulmonary functions, and imaging findings including mucus plug,and no recurrence was observed thereafter. Conclusion:We reported a case of successful switching from omalizumab to mepolizumab for severeasthma with ABPM. Mepolizumab improved not only subjective symptoms, but also radiographic findings.

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PE11-13 The first case of allergic bronchopulmonary mycosis caused by bjerkandera adusta

Kazuya Tone1), Haruhiko Ogawa2,3), Mina Gochi1), Yuko Nagano4), Susumu Saito1), Takuya Akutsu1), Atsuki Furube1), Shunsuke Inaki1),Masamichi Takagi1), Kazuyoshi Kuwano5), Koichi Makimura6) (Department of Respiratory Medicine, The Jikei University School of Medicine, Ka-shiwa Hospital, Japan1); Division of Internal Medicine, Jinchikai Hospital, Japan2); Department of Environmental and Preventive Medicine, Ka-nazawa University, Japan3); Clinical Central Laboratory, The Jikei University School of Medicine, Kashiwa Hospital, Japan4); Division of Respira-tory Medicine, Department of Internal Medicine, The Jikei University School of Medicine, Japan5); Graduate School of Medicine, Teikyo Univer-sity, Japan6))

The filamentous basidiomycete, Bjerkandera adusta , is often isolated from respiratory specimens of patients with unexplained chronic cough.These findings may develop in response to colonization in respiratory tracts with B. adusta and the cough symptom could be improved by itra-conazole in such cases; this disease phenomenon was first proposed by our group in 2009 and is called as fungus-associated chronic cough (Ogawaet al. J Asthma 2009). However, it was not clear whether this fungus was associated with other respiratory diseases. We report here the first caseof allergic bronchopulmonary mycosis caused by B. adusta . A 67-year-old Japanese man with a history of bronchial asthma presented with wors-ening dyspnea and productive cough. He reported a 30-year history of dyspnea that was unrelieved by standard asthma therapy. Findings onchest auscultation included wheezing and attenuated breath sounds. The peripheral blood eosinophils count and total IgE level were both ele-vated, although tests for fungus-specific IgEs, including those for Aspergillus or Candida , were negative. Chest computed tomography revealedbronchial dilatation with mucous impaction and increased bronchial wall thickness in both lung fields. Bronchoscopy was notable for viscous mu-cus impaction observed predominantly both upper lobe bronchi. Grocott’s methenamine silver (GMS) and hematoxylin and eosin (H&E) stainingrevealed Y-shaped septate hyphae and inflammatory cells including eosinophils or neutrophils, respectively, in the bronchoscopy specimen. Myce-lia were isolated from the specimen and identified as B. adusta by direct sequencing of the internal transcribed spacer (ITS) region of the ribo-somal RNA gene. To the best of our knowledge, this is the first patient clinically diagnosed with allergic bronchopulmonary mycosis caused by B.adusta . Symptoms and radiological findings improved in response to oral corticosteroid therapy. Although specific pathogenicity associated withfilamentous basidiomycetes has not been widely recognized, this pivotal case report reveals that B. adusta can result in bronchopulmonary myco-sis. As such, we note that this pathogen is associated with multiple respiratory diseases.

PE11-14 A case of eosinophilic granulomatosis with polyangiitis presenting with central retinal artery occlusion

Hirono Nishiyama1), Tomoko Tajiri1), Shinya Tamechika2), Katsuya Suzuki3), Ryota Kurokawa1), Norihisa Takeda1), Kensuke Fukumitsu1),Yoshihiro Kanemitsu1), Satoshi Fukuda1), Takehiro Uemura1), Hirotsugu Ohkubo1), Ken Maeno1), Yutaka Ito1), Masaya Takemura1), Taio Naniwa2),Akio Niimi1) (Department of Respiratory Medicine, Allergy and Clinical Immunology, Japan1); Department of Rheumatology, Nagoya City Univer-sity, Japan2); Department of Ophthalmology, Japan3))

Introduction: Ophthalmic involvement is infrequent in eosinophilic granulomatosis with polyangiitis (EGPA). Here, we report a case of EGPA pre-senting with central retinal artery occlusion (CRAO). Case Report: A 53-year-old man had been diagnosed with atopic asthma three years agoand was treated with inhaled corticosteroids (ICS) and long-acting β2-agonist (LABA) combination at a primary care clinic. Despite high-doseICS/LABA treatment, the patient often experienced asthma exacerbations which required oral corticosteroids (OCS). The patient was referred toour respiratory clinic 10 months ago. Although step 5 treatment of GINA including leukotriene receptor antagonist, theophilline and maintenanceOCS was initiated, the patient’s asthma remained poorly controlled. As a result of having nasal congestion and dysosmia, the patient was diag-nosed with chronic rhinosinusitis with nasal polyps as a comorbidity and was administered intranasal corticosteroids. However, the patient’sasthma remained poorly controlled. Two months ago, the patient complained of acute diplopia due to abducens nerve palsy of his right eye. No ab-normalities were detected in the eyes or in an MRI imaging of the brain, except for blood vitamin B12 deficiency and worsened eosinophilia (3444/µL). In order to treat diplopia and improve asthma control, vitamin B12 and an anti-interleukin-5 receptor monoclonal antibody, benralizumab 30mg, were administered. Despite improvement of blood eosinophilia (0/µL), the patient complained of acute loss of vision in his left eye, bilateral legpain, lower extremity weakness, and purpura. Fluorescein angiograms revealed CRAO, and a nerve conduction study revealed polyneuropathy.The patient tested positive for myeloperoxidase-antineutrophil cytoplasmic antibody. A skin biopsy for purpura revealed vasculitis. Based on theAmerican College of Rheumatology criteria, the patient was diagnosed with EGPA. Glucocorticosteroids and cyclophosphamide have been admin-istered to treat it. Conclusion: Here, we report a rare case of EGPA presenting with CRAO. CRAO associated with EGPA often has a poor visualoutcome, partly because of delay in diagnosis and treatment. Physicians should consider EGPA as a differential diagnosis of CRAO complicatingeosinophilic asthma.

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Poster Session 12Case report: clinical immunology

PE12-1 Intestinal tissue cytokines analysis in case of a 10 years old boy diagnosed with eosinophilic gastroenteritis

Masako Chiyotanda1), Shigeo Nishimata1), Taro Miura2), Ryuhei Nagao1), Yasuyo Kashiwagi1), Hisashi Kawashima1) (Department of Pediatrics, To-kyo Medical University, Japan1); Department of Pediatrics, Tokyo Medical University Hachioji Medical Center, Japan2))

Introduction: There are reports of analysis of serum cytokines in eosinophilic gastroenteritis in infants, but studies focused on biopsy tissues areless well reported. In this study, we attempted analysis of homogenized tissue cytokines and immunohistochemical analysis of cytokines in biopsytissues of patient diagnosed with eosinophilic gastroenteritis. Case: The case was a 10 year old boy. The patient had abdominal pain, increasedstool frequency and blood stools for one year. Symptoms were exacerbated by ingestion of some food, but the food which caused pain could not beidentified. For this reason, he was referred to our hospital for scrutiny of abdominal pain. His blood tests showed an increase in eosinophil counts,the milk-specific IgE value increased to 0.82 kUA/L and the skin prick test was negative. In the subsequent oral food challenge test, hen’s egg andwheat were negative. Reproducibility of the symptoms was observed in the cow’s milk, and there for was removed. In endoscopy, macroscopicfindings were not observed. Endoscopic biopsy of the colonic mucosa showed eosinophilic infiltration of 20 to 30 cells/HPF in the ileocecal to supe-rior colon. Result: We performed cytokine/chemokine analysis of colorectal mucosal biopsy tissue by a multi-cytokine assay. Cytokine analysisduring the symptomatic period showed a significant increase in IL-5, 7, and 10. Conclusion: In this analysis, IL-5 related to eosinophils and IL-10related to gastrointestinal inflammation varied in homogenized tissue. IL-10, which is known to decrease in ulcerative colitis, increased in thisstudy. We also compared the biopsy tissue cytokines analysis before and after treatment, and consider it with the previous studies.

PE12-2 Identification of allergens causing reactions at the sites of venous access using delayed hypersensitivity assays

Slawomir M Kosinski1), Roberto V Nachajon2) (Division of Allergy and Immunology, St Joseph’s University Medical Center, USA1); Division of Pedi-atric Pulmonology, St Joseph’s University Medical Center, USA2))

We repot two cases of patients who developed skin lesions at the sites of venous access. In both cases the lesions consisted of erythematous, pru-ritic patches involving the area around the catheter and upper part of the extremity. The lesions were not improving after treatment with antihis-tamines, topical or systemic corticosteroids, but resolved within a week after infusions were stopped. In both cases we used patch test of our owndesign in which we incubated the filter paper in saline with pieces of catheters for various length of time before placing the paper in Finn cham-bers on the patients’ back. We used polyurethane catheter (same brand as used in vivo) and silicon catheter as a control. The test was read after48 hours. In case #1 the test was positive with polyurethane, but negative with a silicon. The patient had no more reactions when we started us-ing silicone catheters for subsequent infusions. In case #2 the patch test was negative with both materials. Thus, we performed skin tests withthe disinfectant used to prep the skin before insertion of catheter, which contained chlorohexidine gluconate and isopropyl alcohol. Percutaneousskin test with dilutions of chlorohexidine gluconate from 0.002% to 0.5%, and intradermal skin test with chlorohexidine 0.0002% were negativewhen read after 15 min. However, two days later the patient called us reporting a pruritic skin rash at the site of the test. Thus, we started usingchlorohexidine-free solution prior to subsequent infusions and the patient had no more reactions. In summary, we identified one problematic aller-gen by a patch test, which is recognized as a delayed hypersensitivity assay, and another allergen by a delayed reaction to the percutaneous skintest (PST), which is not considered as a delayed hypersensitivity assay. Nevertheless, the PST is known to trigger delayed reactions, althoughtheir clinical significance is not universally recognized. In addition, we used an innovative method to prepare an allergen for a patch test.

PE12-3 Serum TARC levels before and after treatment for pruritic ordinary scabies

Yukiyasu Arakawa, Risa Tamagawa Mineoka, Koji Masuda, Norito Katoh (Department of Dermatology, Kyoto Prefectural University of MedicineGraduate School of Medical Science, Japan)

Scabies can resemble Th2 immunity-related dermatological diseases, such as atopic dermatitis (AD) and prurigo nodularis (PN). Elevated serumimmunoglobulin E (IgE) levels have been reported during scabies infections, which reduced after the scabies was treated. Here, we report, for thefirst time, a case of pruritic ordinary scabies, involving elevated serum thymus and activation‐regulated chemokine (TARC) levels, which de-creased after the scabies was treated. The patient was an 84-year-old male with with normal IgE levels. Two months before his visit, he developedmarked pruritic rashes and severe itching, resistant to topical corticosteroid therapy and oral anti-histamine treatment, and he was referred toour department. Erythematous nodules were seen all over his body. His serum IgE (488 IU/L (normal range: 0358)) and TARC (1426 pg/mL (nor-mal range: 0449)) levels were elevated, and AD was suspected. Histopathology showed a scabies mite within the epidermis and the perivascularinfiltration of eosinophils within the dermis. The diagnosis of a scabies infection was made. The patient was systemically treated with oral iver-mectin once a week for a total of 4 weeks. At 1 month post-treatment, the prurigo lesions had improved, but he still had persistent itching. How-ever, his serum IgE (462 IU/L) and TARC (763 pg/mL) levels had reduced. At 3 months post-treatment, his itching was finally relieved, and fur-ther reductions in his serum TARC (381 pg/mL) and IgE (350 IU/L) levels were observed. Th2 immunity predominates in human ordinary sca-bies lesions and is accompanied by epidermal expression of TSLP. Eosinophils secrete Th2-inducing cytokines (IL-4), which affect resident den-dritic cells (DCs), enhancing DC activation and promoting a Th2-inducing phenotype. As scabies is frequently misdiagnosed as AD or PN, elevatedserum TARC levels could further delay diagnosis. Thus, clinicians must consider ordinary scabies when examining patients with pruritic noduleswho exhibit elevated serum TARC levels, and the serum TARC level might be a useful marker of the efficacy of treatments for scabies.

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PE12-4 PD-1 blockade might induce eosinophilic pneumonia like eosinophilic granulomatosis with polyangitiis feature

Masanori Harada, Hyogo Naoi, Keisuke Morikawa, Yutaro Ito, Namio Kagoo, Tsutomu Kubota, Koshiro Ichijo, Eisuke Mochizuki,Norimichi Akiyama, Masahiro Uehara, Shun Matsuura, Masaru Tsukui, Naoki Koshimizu (Department of Respiratory, Fujieda Muninciple Gen-eral Hospital, Japan)

Back ground: Immune checkpoint inhibitor (ICI) has been a promising anticancer treatment. Although ICI could have inflammatory side effectsthat involve wide range organs related to the CD4 positive T cell immune reactions, the matter about allergic inflammation has been rarely re-ported. Case: 65-year-old man was diagnosed with kidney carcinoma. Left kidney resection was conducted and then chemotherapy was started.Although several adverse events seemed make it difficulty to be continued, the nivolumab was treated for its good responces. 9 months later,bronchial asthma attack was occurred and then gradually peripheral eosinophil and FeNO was increased. Chest CT scan showed bilateral abnor-mal shadow. Pathological findings with bronchoscopy from lung revealed eosinophil infiltration and severe alveolar haemorrhage, and then abronchial mucosal biopsy from the secondary carina showed smooth muscle hyperplasia and thickened basement membrane with eosinophil. Aparanasal sinus level CT scan showed sinusitis. His nerve conduction study was also indicated the decrease in his right ulnar nerve conduction ve-locity. Finally, EGPA was diagnosed. After steroid therapy was initiated, bronchial asthma and bilateral infiltration on the chest CT scan were im-proved. To be restarted nivolumab treatment, steroids therapy was gradually tapered and then biweekly mepolizumab was administered forEGPA with nivolumab and there have been no bronchial attacks and CT abnormality until now. Conclusion: This was the rare case that was di-agnosed with EGPA by pathological eosinophilic angiitis after ICI treatment. The blockade of PD-L2 or PD-L2/PD1 signaling cascade might be acause of allergic inflammation. The precise mechanisms about allergic inflammation after PD-1 blockade have not been understood, so it needs tobe clarified in the future.

PE12-6 Two cases of interstitial pneumonia with anti-MDA5 antibody in this hospital

Kentaro Tamura1), Ayako Kojima1), Masahiro Yoshida1), Zenya Saito1), Kazuyoshi Kuwano2) (Department of Internal Medicine, Division of Respira-tory Medicine, Atsugi City Hospital, Japan1); Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medi-cine, Japan2))

Introduction: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5a) is specific for clinical amyopathic dermatomyositis(CADM). Most patients with this antibody display rapid progressive interstitial pneumonia and poor prognosis. Methods: We report herein twocases of patients with anti-MDA5a treated in this hospital from October 2016. Results: Case 1 involved a 67-year-old woman who presented withacute dyspnea on exertion, dry cough and fever. She showed mild hypoxemia at rest and Gottron’s sign, but mild myalgia of the proximal upperlimbs without evidence of myositis. C-reactive protein (CRP) was 9.49 mg/dl, creatine kinase (CK) was 269 U/l, ferritin was 721 ng/ml, and anti-MDA5a titer was 2490. Computed tomography (CT) of the chest showed non-segmental multiple consolidations and ground-glass opacities withbronchiectasis showing a subpleural distribution. We diagnosed CADM. As concurrent steroid pulse therapy and tacrolimus proved ineffective,we added cyclophosphamide and direct hemoperfusion using a polymyxin B-immobilized fiber column. However, these therapies proved ineffec-tive, and she died 12 days after admission. Case 2 involved a 46-year-old man with abnormalities on chest X-ray during routine medical examina-tions. He had complained of fever and skin rashes. He showed desaturation on exertion, Gottron’s sign, and mild weakness of the proximal lowerlimbs with evidence of mild myositis. CRP was 0.85 mg/dl, CK was 513 U/l, ferritin was 650 ng/ml, and anti-MDA5a titer was 1680. Chest CT re-vealed many consolidations with bronchiectasis showing a subpleural distribution, and partly along bronchovascular bands. We diagnosed der-matomyositis. Combination therapy with steroid and tacrolimus proved effective. We encountered two patients with anti-MDA5a following oppo-site clinical courses. The difference between cases was that CRP, CK, ferritin, anti-MDA5a titer, and width of interstitial shadows were worse inCase 1, whereas myositis was milder. These factors might have contributed to the prognosis. In fact, some reports showed prognostic factors likethem. Conclusion: The prognosis of interstitial pneumonia with anti-MDA5a is poor, but adequate treatment proves effective in some cases. Fur-ther prognostic factors need to be identified.

PE12-7 Case report: unusual manifestation of lupus erythematous systemic with thalassemia B intermediate and hemolytic autoimmuneanemia

Muhammad Alif Fathur Rachman1), Nova Kurniati2) (Department of Internal Medicine, Moh Hoesin Palembang Hospital, Indonesia1); SriwijayaUniversity, Indonesia2))

Background: Lupus erythematous systemic is autoimmune disease marked by systemic inflammation in organ or immune system. 1000 lupus pa-tient reported 4,8% with manifestation of autoimmune hemolytic anemia, and less than 1% with manifestation of thalassemia Beta. Case Report:21 years old woman, with chief complain of fatigue came to emergency department of Moh Hoesin Hospital, Palembang, Indonesia. Physical examwe found conjungtiva anemia, pale palmar, icteric sclera, liver just palpable, lien on Schuffner V, and epigastric pain. History of blood transfusionsince 5 years old. Systemic lupus international collaborating clinics (SLICC) 2012 total score 5. MEX SLEDAI score is 4. From laboratorium find-ings; Hemoglobin 5,5 g/dl, leucocyte 4,700/mm3, erythrocyte 2,56 x106 mm3, thrombocyte 108.000/L, hemathocryte 18%, MCV 70 fl, MCH 21 pg,AST 59 u/L, ALT 53 u/L, ureum 14 mg/dl, creatinin 0,56 mg/dl, calsium 9,2 mg/dl, natrium 135 mEq/L, kalium 4,0 mEq/L. Analytic hemoglobinis thalassemia Beta intermedia. Discussion: we give high dose immunosuppressant and show good response. It reduce size of lien become Schuff-ner III. And the patient seldom to admission for blood transfusion. Conclusion: when manifestation of lupus is Thalassemia, it gives bad prognosis,but, with early diagnosis and treatment, it give a very good response.

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PE12-9 Systemic sarcoidosis associated with certolizumab pegol treatment for rheumatoid arthritis: a case report and review of the lit-erature

Keigo Koda1), Mikio Toyoshima1), Tsuyoshi Nozue1), Takafumi Suda2) (Department of Respiratory Medicine, Hamamatsu Rosai Hospital, Japan1);Second Department of Internal Medicine, Hamamatsu University School of Medicine, Japan2))

Case Report: A 69-year-old woman presented with appetite loss, fatigue, and fever. She had been receiving certolizumab pegol (CZP) for rheuma-toid arthritis for 6 years. Computed tomography of the chest showed multiple micronodules in both lungs and bilateral hilar and mediastinal lym-phadenopathy. The ophthalmic examination showed the findings of uveitis. Lymphocytosis with an increased CD4/CD8 ratio was seen in bron-choalveolar lavage fluid. Video-assisted thoracoscopic biopsy specimens obtained from the right lung and a right hilar lymph node showed non-caseous epithelioid cell granulomas. Anti-tumor necrosis factor (TNF)-α-induced sarcoidosis was diagnosed, and she was successfully treatedwith cessation of certolizumab pegol and systemic corticosteroid therapy. Discussion: A review of the English-language literature identified 85 re-ported cases of anti-TNF-α agent-induced sarcoidosis. Most underlying diseases for which anti-TNF-α agents were administered included rheu-matoid arthritis, followed by psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel diseases, and so on. More than half of the patientshad been receiving etanercept, followed by adalimumab and infliximab. Only 2 patients had been receiving CZP. Patients who had CZP-inducedsarcoidosis had single organ involvement, such as uveitis and cutaneous lesions. The present case is the first case of CZP-induced typical systemicsarcoidosis. Thirty-six of 85 patients with anti-TNF-α agent-induced sarcoidosis had cutaneous involvement, while only 1 of the 85 patients hadcardiac involvement. In 71 of 85 cases with anti-TNF-α agent-induced sarcoidosis, the anti-TNF-α agents were discontinued, and the sarcoidosisresolved in 36 cases, but it remained stable in 2 cases. The other 33 cases required systemic corticosteroid treatment (SC), and the sarcoidosis re-solved in 32 cases, but it remained stable in 1 case. In 9 of 85 patients, the anti-TNF-α agents were continued with SC, and the sarcoidosis im-proved in all 9 cases. From these observations, anti-TNF-α agent-induced sarcoidosis appears to be manageable with discontinuation of the anti-TNF-α agents with or without SC in most cases. If anti-TNF-α agents are indispensable for the treatment of underlying autoimmune diseases,anti-TNF-α agents can be continued with SC.

PE12-10 Pregnancy-related hemophagocytic lymphohistiocytosis: a report of three cases with assessing cytokines profile

Takahiro Yoshikawa, Kazuaki Noguchi, Mai Nakano, Akio Tamura, Naoto Azuma, Kiyoshi Matsui (Division of Allergology and Rheumatology, De-partment of Internal Medicine, Hyogo College of Medicine College Hospital, Japan)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease that can be fatal in pregnancy. Methods: We report three cases ofpregnancy-related HLH those who had no malignancy and rheumatic diseases with assessing cytokines profile including serum IL-6, IL-18, neop-terin, soluble TNF receptor I and TNF receptor II. Results: Case 1. 30-year-old woman presented at 1 week after treatment of pelvic abscess dueto postoperative complication of cesarean section with fever, hepatic dysfunction, thrombocytopenia, and elevated ferritin. Antibiotic treatmentwas poorly effective, so we considered HLH and started treatment with corticosteroids and calcineurin inhibitors. Case 2. 24-year-old women pre-sented at 36 weeks with fever, acute liver failure, thrombocytopenia, and elevated ferritin. Because symptoms did not improve after cesarean sec-tion, HLH treatment was initiated, including corticosteroids and calcineurin inhibitors. Case 3. 37-year-old women presented at 17 weeks with fe-ver, acute liver failure, thrombocytopenia, and elevated ferritin. Bone marrow biopsy confirmed HLH. HLH treatment was initiated, including cor-ticosteroids and calcineurin inhibitors. Fetal growth restriction was not found, and delivery occurred at 36 weeks. All patients were successfullytreated with glucocorticoids and calcineurin inhibitors. All patients had higher level of serum IL-6 (15.6, 102 and 332 pg/mL), IL-18 (1160, 1140 and1860 pg/mL), neopterin(40, 48 and 111 over mmol/L), and soluble TNF receptor II/I ratio (>5). From cytokines profile of these cases, it was sug-gested that the pathology of pregnancy-related HLH is different from that of adult onset Still’s disease. Conclusion: We presented the first caseseries of pregnancy-related HLH with assessing cytokines profile. Further investigation is needed to evaluate the correct treatment regimens.

PE12-11 Early initiation of mepolizumab for remission induction therapy in patients with eosinophilic granulomatosis with polyangiitis: re-port of two cases

Jun Tamura1), Minami Koriyama2), Mari Yatomi3), Hiroshi Nakajima4), Tomohiro Tamachi1,4) (Department of Allergy and Clinical Immunology,Chiba Rosai Hospital, Japan1); Department of Otolaryngology, Head and Neck Surgery, Chiba Rosai Hospital, Japan2); Department of RespiratoryMedicine, Chiba Rosai Hospital, Japan3); Department of Allergy and Clinical Immunology, Chiba University Hospital, Japan4))

Interleukin-5 (IL-5) plays critical roles in proliferation, survival, and differentiation of eosinophils. Therefore, it is reasonable to target IL-5 for thetreatment of eosinophilic granulomatosis with polyangiitis (EGPA). In the MIRRA trial, the efficacy of mepolizumab has been shown in patientswith relapsing or refractory EGPA at least 6 months after diagnosis. However, it is not known whether early intervention with mepolizumab hasbeneficial effects. We herein report two cases of EGPA treated with mepolizumab in the earlier phase of the disease. The first case was diagnosedas ANCA-negative EGPA based on the presence of eosinophilia (11,475/µl), asthma, heart failure (left ventricular ejection fraction 41%), mononeu-ritis multiplex, and bilateral vocal cord paralysis (BVAS score 21). Methylprednisolone 500mg/day for 3 days followed by prednisolone (PSL) 50mg(1mg/kg)/day was administered. However, eosinophilia (483/µl) reappeared on day 12, and repeated mepolizumab 300mg every 4 weeks was in-troduced, which led to sustained reduction in the eosinophil number, nearly full recovery of mononeuritis multiplex, no exacerbation of heart fail-ure, and partial improvement in vocal cord paralysis. At 13 months, no relapse was observed with the reduction of mepolizumab 200mg every 4weeks and PSL 4mg/day. The second case showed eosinophilia (5,220/µl), MPO-ANCA 132 IU/ml, severe allergic rhinitis, pulmonary infiltrates,mononeuritis multiplex with purpura, and musculoskeletal symptoms (BVAS score 19). PSL 45mg (1mg/kg)/day for 2 weeks promptly improvedeosinophilia and symptoms. However, tapering PSL 35mg led to relapse with eosinophilia (2,153/µl) and new-onset mononeuritis multiplex withpurpura on the other foot. On day 33, mepolizumab 300mg was introduced. The disease activity including mononeuritis multiplex was success-fully controlled without increasing PSL dose, and PSL dose was reduced to 15mg/day at week 19. Considering our cases, the early initiation of me-polizumab for the treatment of EGPA is a promising therapy to investigate.

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PE12-12 Eosinophil extracellular trap formation in chronic granulomatous disease

Yui Miyabe1), Michihiro Yano2), Mineyo Fukuchi1), Chikako Furutani1), Yuki Moritoki1), Tomoo Saga1), Tsutomu Takahashi2), Shigeharu Ueki1) (De-partment of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Japan1); Department ofPediatrics, Akita University Graduate School of Medicine, Japan2))

Background: Human neutrophils and eosinophils can undergo reactive oxygen species (ROS)-dependent cell death program called extracellulartrap cell death (ETosis) that release filamentous DNA called extracellular traps (ETs). Chronic granulomatous disease (CGD) is one of the congeni-tal immunodeficiency syndromes, which has a genetic abnormality in the molecules that constitute NADPH oxidase. Neutrophils from patientswith CGD are known to lack ETosis capacity due to a defect in ROS production. However, no study has been reported regarding eosinophil ETo-sis in CGD patient. Method: Neutrophils and eosinophils were isolated from peripheral blood in a patient with CGD who has mutation in CYBBgene and a healthy donor. ETosis was induced by stimulation with PMA, a potent ETosis inducer for both neutrophils and eosinophils. ROS pro-duction was assessed by APF fluorescence intensity. SYTOX staining was used to detect cell death and immunofluorescence staining for citrulli-nated histone was used to detect ETs. Results: In line with previous reports, neutrophils from CGD patient did not produce either ROS or ETs inresponse to PMA. In eosinophils from CGD patient, ROS production was also inhibited, whereas ETs were induced similar level to those ofhealthy donor. Diphenylene iodonium (DPI) which inhibit NADPH oxidase completely suppressed PMA-induced ROS production and ET forma-tion in neutrophils and eosinophils from healthy donor and CGD patient. Conclusion: Neutrophil and eosinophil ETosis might be regulated by dif-ferent signaling pathways.

PE12-13 A case of muckle-wells syndrome with the skin erythema dominantly infiltrated by lymphocytes

Saori Kadowaki, Takeshi Kimura, Mayuka Shiraki, Norio Kawamoto, Hidenori Ohnishi (Department of Pediatrics, Gifu University Graduate Schoolof Medicine, Japan)

Background: In general, the urticarial like erythema is observed in the patients with cryopyrin-associated periodic syndrome (CAPS), and thehistological pattern of the skin lesions consists of the neutrophilic infiltration. In this study, we report a boy case of Muckle-Wells syndrome(MWS) with erythema dominantly consisted of the lymphocyte infiltration. Case Report: A 15-year-old boy had recurrent non-itchy urticaria-likeskin rash on his lower limbs since childhood. His elder brother also had a similar rash. At the age of 13, he was referred to our hospital because ofrecurrent fever and the persistent elevation of the serum CRP levels after acute bronchitis. The skin biopsy of his rash showed the infiltration oflymphocytes at the border of the epidermis, around blood vessels, and appendages. Genetic analysis for hereditary autoinflammatory disease re-vealed the known heterozygous mutation, R260W, of the NLRP3 gene. Thus, the diagnosis of MWS was confirmed by this result and the compat-ible clinical course other than the result of a skin biopsy. The production level of IL-1β from the patient’s peripheral blood mononuclear cells atlow temperature (30℃) for 24 hours was evaluated, and an increase of IL-1β production was observed. He was administered canakinumab 150mg every 8 weeks and his symptoms are in remission. Discussion: The histopathological pattern of skin in this case was close to that of NLRC4 -associated autoinflammatory diseases, but the comprehensive genetic analysis identified not NLRC4 but NLRP3 mutation. Because the clinicalfeatures of this patient were typical of MWS, but the histopathological pattern of skin was atypical, it is difficult to make a definitive diagnosis ofCAPS based on only histopathological findings of skin lesions. It is suggested that the genetic analysis is necessary for a definitive diagnosis in ad-dition to the clinical features.

PE12-14 Lung granulomatous disease in a patient with GATA2 mutation

Motoko Yasutomi1), Taihei Hayashi1), Koji Suzuki1), Genrei Ohta1), Yasuhiro Watanabe4), Toshihiro Takeda2), Akitoshi Okada3), Yusei Ohshima1) (De-partment of Pediatrics, Faculty of Medical Sciences, University of Fukui, Japan1); Third Department of Internal Medicine, Faculty of Medical Sci-ences, University of Fukui, Japan2); Division of Thoracic Surgery, Department of Surgery, University of Fukui, Japan3); Department of Pediatrics,Fukui Red Cross Hospital, Japan4))

Background: Heterozygous germline GATA2 mutations cause monocytopenia, immunodeficiency and predispose to MDS/leukemia. Case: A 12-year-old boy developed recurrent fever, cough and dyspnea for 6 months. Chest X-ray revealed bilateral ground glass opacity. Blood examinationshowed monocytopenia (0-2.5%) with low levels of IgA (29 mg/dl). Autoantibodies were not detected. He developed erythema after starting of an-tibiotics and was treated with prednisolone (30mg/day), which improved eruption and pneumonia as well. However, tapering of prednisolone in-duced recurrence of pneumonia. Computed tomography showed multiple bilateral lung nodules after the third recurrence. Lung biopsy revealedaccumulation of Langhans type giant cells, granuloma formation and CD4+ T cell infiltration. Culture of fungi and bacteria were negative in bron-choalveolar fluid and lung specimen. Detection of DNA for mycobacteria, tuberculosis, cytomegalovirus, EB virus and Pneumocystis jiroveciiwere negative. FDG-PET examination did not show typical sarcoidosis pattern and other organ involvement except lung. Gene analysis revealeda reported hetero missense mutation of GATA2 (p.R361C). He also showed B and NK lymphopenia. He has been doing well with taking itracona-zole, clarithromycin, prednisolone (10mg/day), and sulfamethoxazole/trimethoprim. He has no evidence of MDS but is waiting for the matched do-nor for hematopoietic stem cell transplantation. Discussion: Patients with GATA2 mutation often have lung manifestation mainly caused by in-fection such as mycobacteria. However, this patient has no evidence of chronic infection and showed granulomatous lung disease similar to pa-tients with common variable immunodeficiency. Impaired immune function including B lymphopenia might be a possible mechanism of lung dis-ease in this patient. Conclusion: Granulomatous lung disease can be a comorbidity of GATA2 mutation.

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PE12-15 Long-term follow up of a patient with hyper-IgE syndrome and STAT3 mutation: clinical complications, allergic manifestationsand specific IgE antibodies

Rumiko Shibata1), Masako Kadowaki2) (Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital, Japan1); Departmentof Internal medicine, National Hospital Organization, Fukuoka National Hospital, Japan2))

Long term follow up patients with Hyper-IgE syndrome (HIES) have been poorly investigated. We present a case report of patient who had recur-rent staphylococcal infections, elevated serum IgE and diagnosed with HIES at the age 16. He had eczema, nail candidiasis and staphylococcal in-fections (cold skin abscesses, pneumonia with lung abscesses and lymphadenitis) from early childhood. After 26 years old, he suffered from fewStaphylococcal infections, mild eczema and left femur head atrophy with arthritis and osteonecrosis. At the age 29 and 49, he suffered from malig-nant lymphoma (B cell lymphoma) of cervical lymph node which treated completely by surgery and chemotherapy. Sulfamethoxazole/trimethoprim, cefdinir and fluconazole take it continuously for prophylaxis against Staphylococcus aureus and candida infection. The clinical phe-notype of NIH score was 64. He works as an office worker at 54 years old now. By the genetic screening of STAT3 mutation, mutate of transacti-vation domain in exson22 (loss of function mutation) was found. Immunological findings showed high levels of serum IgE (50000～26000U/ml), de-creased IgG subclass 3, elevated CD45R and decreased CD16 of NK cell. Delayed type hypersensitivity tests were negative against to PPD, Can-dida, and mumps and positive to PHA. Allergic manifestations showed eczematous dermatitis and food allergies (oral allergy syndrome). The spe-cific IgE antibodies against many foods (egg white, peanut, kiwi, banana and avocado), latex, candida and Staphylococcus aureus cell wall protein(SCWP) were persisted with high level. For the measurement of Staphylococcus specific IgE antibody, SCWP was prepared as antigen from S.aureus 209p 65G (protein A deficient strain).

PE12-18 A pediatric case of productive cough caused by mutations in DNAH9

Kazuhiko Takeuchi1), Yifei Xu1), Kazuki Chiyonobu1), Hisami Kubo1), Guofei Feng1), Satoru Ogawa2), Makoto Ikejiri3), Kaname Nakatani4),Satoko Usui5), Sawako Masuda5), Mizuho Nagao6), Takao Fujisawa6) (Department of Otorhinolaryngology, Mie University, Japan1); Electron Micros-copy Research Center, Mie University, Japan2); Department of Central Laboratories, Mie University Hospital, Japan3); Department of GenomicMedicine, Mie University Hospital, Japan4); Department of Otorhinolaryngology, Mie National Hospital, Japan5); Institute for Clinical Research, MieNational Hospital, Japan6))

Background: Causes of productive cough in pediatric patients are not always identified. Recently, it was reported that DNAH9 polymorphismswere associated with asthma and bronchial hyperresponsiveness in response to early life tobacco smoke exposure. Case: A 5-year-old girl was re-ferred to our hospital because of recurrent productive cough. The first year of her life was uneventful. Since she was one year and six months old,she had repeated episodes of productive cough after she had common cold. Procaterol and inhaled steroid therapy was not effective. Nose X-rayshowed opacification in her right maxillary sinus, but her chest X-ray was normal. At the age of five, her nasal nitric oxide concentration showedextremely low value (44 ppb). Primary ciliary dyskinesia was suspected and the following examination was performed. Electron microscopy of abiopsy specimen from her nasal mucosa revealed loss of the outer dynein arms. Whole-exome analysis of her genome revealed compound het-erozygous mutations in DNAH9 (NM_001372.3): c.[1298C>G];[5547_5550delTGAC], (p.[Ser433Cys];[Asp1850fs]); neither of which has been reportedin the literature. Discussion: DNAH9 and its partner heavy chain DNAH5 localize to type 2 outer dynein arms of the distal cilium. DNAH9-mutated nasal respiratory epithelial cilia show a reduced beating frequency with a subtle beating pattern defect affecting the motility of the distalcilia portion. Unlike typical cases with primary ciliary dyskinesia, cases with DNAH9 mutations are reported to have subtle respiratory signs andsymptoms, This is the first case with DNAH9 mutations who is situs solitus. Mutations in DNAH9 may be a cause of productive cough in pediatricpatients. Conclusion: DNAH9 compound heterozygous mutations were found in a pediatric patient with recurrent productive cough. Mutation ofthis gene might play a role in cough in pediatric patients.

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Poster Session 13Case report: food allergy

PE13-1 A case of pollen-food allergy syndrome with intractable oral swelling

Daiki Sakamoto1), Satoko Hamada1,2), Yoshiki Kobayashi1,2), Akihiro Shimamura1), Akira Kanda1,2), Mikiya Asako1,2), Hiroshi Iwai1) (Department ofOtorhinolaryngology, Kansai Medical University, Japan1); Allergy Center, Kansai Medical University, Japan2))

Background: Pollen-food allergy syndrome (PFAS) is a common adverse reaction occurring within a few minutes after the consumption of un-cooked fruits and vegetables in patients with a pollen allergy. PFAS is an immunoglobulin E (IgE)-mediated allergic disease caused by cross-reactions among pollens and vegetables. The treatment for PFAS involves the avoidance of the consumption of the triggering food in a raw state,while other therapeutic options for PFAS are still under discussion. Here, we show a patient with intractable PFAS who was treated with sublin-gual immunotherapy (SLIT). Case Description: A 12-year-old boy who had multiallergen pollinosis developed oral swelling after eating freshfruits and vegetables, such as oranges, apples, peaches and tomatoes one year ago. Serum-specific IgE antibodies to 8 kinds of pollen, 3 kinds offruit and 3 kinds of vegetables were detected. He showed positive reactions to several vegetables and fruits on the prick-to-prick skin test andalso tested positive on component-resolved diagnosis, such as pectate lyase, profilin and PR-10. We educated the patient to avoid fresh fruits, vege-tables and treated him with pharmacotherapy such as antihistamines, intranasal corticosteroids and antileukotriene to reduce the symptoms. Fur-thermore, we treated him with Japanese cedar pollen (JCP) sublingual immunotherapy (SLIT) as he suffered from severe nasal symptoms duringthe JCP dispersal season. These treatments improved nasal symptoms; however, persistent oral swelling remained. Additional omalizumab treat-ment reduced his oral swelling, suggesting that the combination therapy of SLIT for targeting the allergen component and omalizumab may beeffective for refractory PFAS patients.

PE13-2 A reaction to RACOLNF due to cow’s milk allergy: a report of two cases

Yoko Inoue, Kaito Goto, Yoshiki Kitani, Ayumi Tsukahara, Yuki Koto, Takahiro Kojima (Department of Pediatrics, St Marianna University Schoolof Medicine, Japan)

Background: RACOLⓇNF (RC), a cow’s milk-based liquid intended for enteral use, is used extensively in Japan and Korea. Prescribing RC for pa-tients with cow’s milk allergy (CMA) is harmful to the patients’ health because RC is primarily composed of cow’s milk. However, the associationbetween RC and CMA is not widely recognized because there are limited cases in which RC caused an immediate allergic reaction. The followingcases pertain to two children diagnosed with CMA after RC ingestion. Case reports: (1) A 1-year-old breast-fed boy (gestational age 39 weeks;birth weight 3152g) with severe motor and intellectual disabilities due to neonatal asphyxia was admitted to a hospital. He had severe eczemasince 4 months of age and a skin prick test revealed positive results; hence, the local doctor advised eliminating hen’s eggs and cow’s milk from hisdiet. The child had an anaphylactic reaction after consuming RC to promote weight gain. The sIgE to cow’s milk was 4.4 UA/ml. (2) A 3-year-oldgirl (gestational age 26 weeks; birth weight 676g) had necrotizing enterocolitis on the 16th day of life. After repeated intestinal perforation, 6 surgi-cal interventions resulted in short bowel syndrome, requiring total parenteral nutrition. She was only fed an elemental diet and her mother’s milk.For weight gain after surgery, RC was administered, but it caused generalized urticaria. The sIgE to cow’s milk was 12.1 UA/ml. To find a safe en-teral formula, a food challenge test was performed through an elemental diet tube using TwinlineⓇ-NF (a formula composed primarily of caseinhydrolysate), which resulted in anaphylaxis. However, the food challenge test result was negative for a soybean-based enteral formula (Hine E-GelⓇ). Her weight increased after using Hine E-GelⓇ; hence, there was no need for total parenteral nutrition. Conclusion: Prescribing RC for chil-dren who have never consumed cow’s milk should be deliberate. If children with CMA require enteral feeding, supplying another enteral nutri-ent, such as an elemental diet or that composed mainly of soy protein, is needed.

PE13-3 Two neonatal cases of food protein-induced enterocolitis syndrome with pale stool and transient biliary dilatation

Eishi Makita1), Sae Kuroda2), Kae Itabashi1), Daisuke Sugawara1), Hiroaki Sato1), Ko Ichihashi1) (Department of Pediatrics, Saitama Medical CenterJichi Medical University, Japan1); Department of Pediatrics, Saitama Red Cross Hospital, Japan2))

Background: Food protein-induced enterocolitis syndrome (FPIES) is an IgE-independent allergic disease that manifests with gastrointestinalsymptoms such as vomiting and diarrhea.Methods:We describe two neonatal cases of FPIES presenting with transient biliary dilatation and palestool, which is the first report. Results: Patient 1 was a girl with a gestational age of 34 weeks and birth weight of 2206 g. Oral feeding with cow’smilk formula was introduced from the day of birth. Pale stool was observed on day 7. She vomited repeatedly after taking cow’s milk formula andexhibited extreme lethargy, bloody stools, and diarrhea on day 8. Abdominal ultrasonography revealed dilatation of the biliary tract. The patientwas suspected of having FPIES caused by cow’s milk proteins. Enteral feeding comprising breast milk or extensively hydrolyzed casein formulawas initiated from day 10, and no recurrence of symptoms was observed. Patient 2 was a girl with a gestational age of 39 weeks and birth weightof 3328 g. Oral feeding with cow’s milk formula was introduced from the day of birth. She vomited repeatedly after taking cow’s milk from day 4.In addition, she presented with bloody stools, diarrhea, and extreme lethargy on day 7. Milk feeding was discontinued due to suspected FPIEScaused by milk protein. Abdominal ultrasonography revealed biliary dilatation on day 15. Enteral nutrition comprising breast milk or extensivelyhydrolyzed casein formula was initiated from day 16, and no vomiting or bloody stools were observed. Although pale stools were identified on day23, this symptom, as well as biliary dilatation, had disappeared by day 28. Biliary dilatation and pale stools improved over time, and there were noorganic disorders of the biliary tract. Both cases were later diagnosed with FPIES in accordance with the diagnostic criteria. Conclusion: Biliarydilatation and pale stools may be observed in patients with FPIES. Hence, it is necessary to consider neonatal gastrointestinal allergies in the diag-nosis of conditions exhibiting biliary dilatation and/or pale stools.

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PE13-4 A case of triplets who developed peanut allergy on the same day

Kenta Otsuji1), Taiki Nagatsuka2), Kazunori Sakai1), Ryoko Amazumi1), Chiaki Higa1) (Department of Pediatrics, Okinawa Kyodo Hospital, Japan1);Department of Intern, Okinawa Kyodo Hospital, Japan2))

The case was three 2-year-old triplets. The second and third of the three were monozygotic. Regarding food allergy, all of three children had epi-sodes of developing redness around the mouth due to ingestion of heated eggs. Eggs were removed from their diet, but they could eat processedegg products freely. All of three had mild bronchitis asthma. The 2nd and 3rd child had mild atopic dermatitis. None of them had gotten skin orblood allergy tests. One day, the three ate peanut butter bread simultaneously. The first child developed facial redness 30 minutes after ingestionof several mouthpieces. The second child began to have redness around the mouth and gradually developed systemic redness, decreased vitality,cough, and nasal discharge 15 minutes after ingestion of one mouth. The third child began to have facial redness and gradually developed sys-temic redness, decreased vitality, nasal discharge, and abdominal pain 15 minutes after ingestion of one mouth. It was their first time to have pea-nuts for all three children. On a later date, we examined specific IgE. The peanut specific IgE was 0.25, 8.87, and 8.15 in order from the first child.The Ara h 2 specific IgE was 0.28, 5.93, and 8.45 in order from the first child. Based on medical history and specific IgE results, we diagnosed thatall three children developed peanut allergy at the same time. There have been no reports of triplets developing peanut allergy simultaneously.Twins and triplets tend to eat the same food on the same time. When giving foods that are prone to allergies for the first time, it may be necessaryto devise ways of giving foods one person at a time on different days, or starting with a small amount at a different timings of the day.

PE13-5 Home-based, slow up-dosing oral immunotherapy for hen’s egg allergy in an adult patient

Satoshi Horino, Kei Uneoka, Masato Nihei, Haruka Aki, Katsushi Miura (Department of Allergy, Miyagi Children’s Hospital, Japan)

Background: Standard therapy for food allergies involves avoiding causative foods until a patient has outgrown their allergies. Oral immunother-apy (OIT) is an optional treatment for children unlikely to outgrow their food allergy. However, information about OIT in adult patients with foodallergies is limited. Herein, we report a case of severe hen’s egg allergy (HEA) in an adult who tried home-based, slow up-dosing OIT, reported tohave been tolerable and effective in children. Case Report: A 20-year-old woman with HEA experienced repeated anaphylaxis since childhood ifshe consumed a small quantity of hen’s egg, so she completely avoided hen’s eggs. She also had atopic dermatitis. She requested treatment forHEA and was admitted to our hospital. Written informed consent for OIT was obtained. She underwent inpatient oral food challenge (OFC) with10 g boiled egg yolk and presented lip swelling and abdominal pain. OFC with 1 g egg yolk the following day induced no adverse reaction. OITwas initiated using a home-based, slow up-dosing protocol. She was equipped with an automatic adrenaline injector and antihistamines andtrained in when and how to properly administer them. She consumed 1 g of boiled egg yolk at home every day, increasing this by 5%10% every 2weeks. She started 0.5 g boiled egg white after reaching a whole egg yolk. She stopped consuming egg if she had an infection, fatigue, or other un-favorable physical condition. If adverse reactions occurred, the daily dose was decreased, as determined appropriate by her attending doctors. Af-ter 59 months, she could eat an entire boiled egg. Anaphylaxis occurred once, 30 months after initiation of OIT. Mild immediate reactions oc-curred frequently; however, these symptoms stopped 43 months after starting OIT. Conclusion: Home-based, slow up-dosing OIT might be appli-cable for adults with severe HEA. Allergic reactions may be induced by the therapy; therefore, it should be performed with appropriate equip-ment and education for patients, in case of emergency.

PE13-6 Dupilumab for treatment of severe asthma and food allergy

Junichiro Tezuka, Takuya Oda, Kota Ikari, Masaru Kawamura, Moeri Tsuji (Department of Allergy and Pulmonology, Fukuoka Children’s Hospi-tal, Japan)

Introduction: Dupilumab is a fully human monoclonal antibody, which acts against the α subunit of the interleukin (IL)-4 receptor that inhibitsIL-4 and IL-13 signaling. This drug was first approved as a biological agent to treat atopic dermatitis (AD) and was subsequently approved in Ja-pan. Currently, this antibody is indicated for the treatment of patients (>12 years of age) with moderate-to-severe bronchial asthma (BA). How-ever, to date, no study has investigated its potential role in immunoglobulin (Ig) E-mediated food allergies. Case:We present the case of a 12-year-old boy with a history of severe BA, allergic rhinitis, chronic urticaria, mild AD, and food allergies (hen’s egg and cow’s milk). Although he hadavoided allergic foods, he often developed anaphylaxis. Despite the administration of high-dose inhaled corticosteroids and long-acting beta-agonists, he presented with acute exacerbation of BA necessitating hospitalization several times a year. Omalizumab use was contraindicated ow-ing to his high serum total IgE levels. Dupilumab therapy was initiated for severe BA (Asthma Control Test [ACT] score=15). He received an in-itial dose of 600 mg, followed by 300 mg every 2 weeks. Chronic urticaria improved after 2 weeks of treatment, and AD and BA improved after 1month of treatment (ACT score=23). He continued oral immunotherapy without anaphylaxis after initiating dupilumab. His food-specific IgE anti-body titer decreased 6 months later along with elevation of the threshold for the oral food challenge test. In conclusion, dupilumab may serve as anew therapeutic option for severe BA concomitant with food allergies.

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PosterSession

PE13-7 A case of fish allergy to parvalbumin successfully treated with oral immunotherapy using cooked, hypoallergenic fish

Tsukasa Ugajin1), Yukihiro Kobayashi2), Kaoru Takayama3), Hiroo Yokozeki1) (Department of Dermatology, Tokyo Medical and Dental University,Japan1); Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Japan2); Department of Dermatology,Saiseikai Kawaguchi General Hospital, Japan3))

A 20-year-old Japanese female presented with a 2-year history of urticaria on her hands and upper extremities after touching fish, especially horsemackerel. Three months later, she presented with throat and gut discomfort after eating fish. She had a history of atopic dermatitis from child-hood. She studied cooking at university for 3 years. In laboratory tests, IgEs against various kinds of fish were detected. An ELISA revealed IgEreactivity to mackerel parvalbumin but not collagen. Stimulation with mackerel parvalbumin also increased CD203c expression on blood baso-phils, whereas heat-inactivated parvalbumin hardly increased. She was diagnosed with a fish allergy sensitized to parvalbumin, and was subse-quently subjected to oral immunotherapy using cooked fish (120 ℃, 60 min) in which majority of parvalbumin was heat-inactivated. She ingestedgradually increased amount of cooked fish in terms of parvalbumin (12 mg/day for 6 months; 22mg/day for 6 months; 33mg/day for 6 months; 44mg/day for 6months). In course of two-years treatment, CD203c induction by stimulation with mackerel parvalbumin was temporally increased inthe early initial phase, and then gradually decreased to 12.4% of baseline levels. Moreover, she could ingest much more amount of fish than theamount which had caused allergic reaction at the early stage. Thus, oral immunotherapy using cooked, hypoallergenic fish might be effective forthe treatment of fish allergy to parvalbumin.

PE13-8 Two cases of anaphylactic reaction to chamomile tea in a patient with mugwort pollinosis

Michiyo Nakagawa, Miho Hanada, Akemi Hamabata, Hiroo Amano (Department of Dermatology, Iwate Medical University, Japan)

Case1: A 65-year-old Japanese woman was referred to our department because of urticaria, vomiting and dyspnea that had occurred 30 min afterdrinking chamomile tea. Her medical history included pollinosis, diabetes and hyperlipidemia. According to the ImmunoCAPⓇ (Thermo FisherScientific, Uppsala, Sweden) test, specific IgE was positive for mugwort (class 4). The serum IgE levels for mugwort was Art v 1 (class 2). The pa-tient showed a positive reaction to chamomile tea leaves in skin prick test (SPT). Chamomile tea is often prepared using German chamomile (Ma-tricaria chamomilla). However, as this plant was not available in Japan, the SPT was performed using feverfew (Tanacetum parthenium), a speciesclosely related to German chamomile. The sample was divided into the tubular petals at the center where pollen adhered and tongue petals. Thetubular petals were positive both non-heating and heating, while the tongue petals were only positive with non-heating. The tubular petals pro-duced a stronger positive reaction than the tongue petals. Case2:A 56-year-old Japanese woman was referred to our department because of tinni-tus, abdominal pain, and impaired consciousness caused a traffic accident, that had occurred 1hour after drinking chamomile tea. A history of foodallergies were crabs, sea squirts, mushrooms, and japanese butterbur scape. She developed urticaria and dyspnea in dandelion fields. Accordingto the ImmunoCAPⓇ test, specific IgE was positive for mugwort (class 3). The serum IgE levels for mugwort was Art v 1 (class 2). The patientshowed a positive reaction to chamomile tea leaves, butterbur scape male flower both non-heating and heating in SPT. Conclusion: The allergiccomponent responsible for mugwort-chamomile association is Art v 1. In our cases, Art v 1 was both positive. We did not perform a suppressiontest to confirm the cross-antigenicity relationship, as it may have caused a cross-reaction with chamomile as a sensitizing antigen for mugwortpollen.

PE13-9 Device of safe food load test without hospitalization

Kanae Ogura (Department of Pedistrics, Kyotoyawata Hospital, Japan)

Objective: To find out safe method to continue food load test with patients’ deslike already don’t couse anaphylactic shock to very small amountwithout hospitalizatin. Methods: To roll patients’ allergen free food with like to load food test with patients’ dislike. Results: 5 years old boy haswheat, egg, milk and fruit allergies. His allegy test values are IgERIST1264IU/ml, wheat class6 IgERAST∪100UA/ml, ω5 gliagin class4 IgER-AST32UA/ml, gluten class6 IgERAST∪100UA/ml. He has had anaphylaxis episods of wheat and egg before he was 1 years old. Weat load testhad been done these 2 years increased by 0.5cm every 2 to 4 weeks to avoid anaphylactic shock without hospitalization, becouse pediatric depart-ment of Kyotoyawata hospital is outpatients consultation only. After he could eat 8cm of boiled udon, he showed anaphylactic symptoms everyboiled udon load tests even if less amount of boiled udon. Then boiled udon completely roll with his allergen free favorite bacon or ham, he couldeat without noticing eating boiled udon. Then he was able to continue boiled udon load test. Conclusions: Doing patients’ dislike food load testwithout hospitalization need some devises. To roll with favorite bacon or ham and increase by very small amount are effective devises to continuesafe boied udon load test with dislike without hospitalization.

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PE13-10 Two cases of Down’s syndrome with chronic cow’s milk-induced FPIES, one case complicated by hypovolemic shock and cere-bral hemorrhage

Urara Tsukagoshi1), Mayumi Araki1), Tamaki Ito1), Yuki Tsumura1), Nobuhiko Taguchi1), Ichiro Nomura2), Hideaki Morita3), Masayuki Akashi4) (De-partment of Pediatrics, Keiyu Hospital, Japan1); Division of Eosinophilic Gastrointestinal Disorders, National Research Institute for Child Healthand Development, Japan2); Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Ja-pan3); Department of Pediatrics, Keio University Hospital, Japan4))

Background: Recently, several cases of food protein-induced enterocolitis syndrome (FPIES) with Down’s syndrome are reported in Japan, al-though their association and characteristics are not fully understood. Here, we report clinical features of 2 chronic FPIES with Down’s syndrome.Case Summary: Case 1: A boy was born with Down’s syndrome weighing 2560g. At day 14 he weighed 2460g under mixed feeding and hismother was instructed to add more formula milk. Diarrhea appeared and soon he drank less, cried weaker and seemed skinny. He revisited to ourhospital at day 21 weighing 1790g with gasping respiration, hypovolemic shock, hypoxemia and metabolic acidosis. He required aggressive fluidresuscitation and mechanical ventilation. He had seizures and MRI revealed cerebral hemorrhage. Amino acid-based formula was introducedbased on suspicion of FPIES. At 7 months old, the diagnosis of FPIES was confirmed by oral food challenge (OFC) with 5ml of formula milk whichinduced vomiting, diarrhea and increased neutrophil count after 2 hours. At 2.5 years old, he became to tolerate 50ml of cow’s milk. Except of con-genital deafness, he has no obvious neurologic sequelae. Case 2: Another Down’s syndrome boy was born with birth weight of 2814g. He wasformula-fed with diarrhea and vomiting once in two days, weighing only 3220g at day 49. He gained weight after the introducing of amino acid-based formula in suspicion of FPIES. When he was 15 months old, we clinically diagnosed FPIES by OFC with 100ml of formula milk which in-duced recurrent vomiting and increased neutrophil count after 2 hours. At age of 2, he had not yet achieved tolerance and have delays in neuro-logical development. Conclusion: We experienced 2 cases of chronic FPIES with Down’s syndrome with diarrhea and poor weight gain duringtheir early infancies. Diagnosis of FPIES were confirmed by OFC after having improvement of their symptoms with elimination of cow’s milk. In-cidence and severity of FPIES might be higher in Down’s syndrome.

PE13-11 Nutritional management of atypical food protein-induced enterocolitis syndrome caused by cow’s milk formula: a case report

Tomoyuki Arima, Yutaka Takemura, Hiroki Masumi, Koji Yamasaki, Megumi Nagai, Keisuke Sugimoto (Department of Pediatric Kindai Univer-sity Faculty of Medicine, Japan)

Introduction: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE)-mediated food allergy. Some patients withspecific IgE antibodies, recognized as atypical FPIES, have been reported. In infancy with atypical FPIES, the appropriate nutritional manage-ment is not well understood. Case Report: A premature male infant (gestational age 29±0 weeks; birth weight 1078 g) developed abdominal dis-tention and vomiting on the 22nd postnatal day. He had eosinophilia (white blood cells: 16,310/µL, eosinophils 48.5%) and increased milk-specificIgE antibody levels (21.7 UA/mL). His symptom improved after avoidance of cow’s milk formula (CMF); thereafter, an oral food challenge test wasconducted, following which the symptoms reappeared. Taken together, we diagnosed him with atypical FPIES. Subsequently, his nutrition wasmostly changed to a hydrolyzed formula while continuing to feed him CMF once a day. Since no allergic symptoms were observed, he was dis-charged 4 months after birth. At every regular check-up, we gradually increased the frequency of CMF feedings per day to reach a complete re-placement with CMF by 8 months of age. No symptoms of FPIES or anaphylaxis occurred during this period, and his growth and developmentwere also good. The eosinophil peripheral blood sample count was maintained at less than 10%. In addition to the CMF, he could consume dairyproducts at the age of 1, and the milk-specific IgE antibody titer decreased to 2.66 UA/mL. Discussion: For infants with atypical FPIES, to con-firm the volume of CMF available to initially intake and how to continue to feed it may help prevent the development of IgE-mediated milk aller-gies, resulting in healing the FPIES without a non-allergenic response.

PE13-12 Omalizumab for pollen-food allergy syndrome: a case report

Natsuko Masumoto1), Rieko Higashijima1), Momoko Sakurai1), Junichiro Tezuka2), Yoshito Ishizaki1) (Department of Pediatrics, National Hospital Or-ganization Fukuokahigashi Medical Center, Japan1); Department of Allergology and Respiratory Medicine, Fukuoka Children’s Hospital, Japan2))

Pollen-food allergy syndrome is caused by pan-allergens such as PR-10 and profilin, and a variety of vegetables and fruits are responsible. If sev-eral food items have to be removed from the diet, the patient’s quality of life will decrease. Omalizumab has been reported to be helpful in themanagement of food allergies and allergic rhinitis. In Japan, omalizumab has recently been covered by insurance for seasonal allergic rhinitis.Here, we report the case of a patient with severe cedar pollinosis and pollen food allergy who was administered omalizumab. Case Presentation:A 13-year-old boy was diagnosed with Japanese cedar pollinosis at the age of five. Pharyngo-laryngeal discomfort, breathlessness, and cough wereobserved following ingestion of many vegetables and fruits. His specific Immunoglobulin E antibodies values (UA/mL) were as high as 100.0, 71.6,3.3, and 11.0 following Japanese cedar, alder, soybeans, and Gly m 4 ingestion, respectively, and he was diagnosed with pollen-food allergy syn-drome. From February to June every year, in addition to allergic rhinitis and conjunctivitis, cough and discomfort persisted for about 2 h aftermeals. The patient underwent sublingual immunotherapy for cedar pollinosis; however, he suffered from similar symptoms and continuation oftherapy was difficult. When the patient was administered omalizumab 450 mg every 2 weeks for cedar pollinosis from February to March, his pol-linosis symptoms were alleviated, and almost no oral allergy symptoms appeared. Conclusions: Omalizumab is effective in ameliorating symp-toms of both seasonal allergic rhinitis and pollen-food allergy and improves the quality of life of the patient.

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PosterSession

PE13-13 Dupilumab induces tolerance in gastrointestinal allergy; a case report

Naoya Arakawa1), Daisuke Shigeta2), Hisako Yagi1), Mariko Shimizu3), Takumi Takizawa1), Yoshiyuki Yamada3) (Department of Pediatrics, GunmaUniversity Graduate School of Medicine, Japan1); Saku Central Hospital Advanced Care Center, Japan2); Gunma Children’s Medical Center, Ja-pan3))

Background: Eosinophilic gastroenteritis (EGE) is a rare disease which is characterized by food-induced gastrointestinal (GI) symptoms, eosino-philia, and infiltration of eosinophils into GI tract.Methods:We used dupilumab to a 15-year-old girl case with EGE and bronchial asthma. Results:She had a history of IgE-dependent food allergies until 5 years of age and poorly controlled asthma. She developed eosinophilia (～15000/µL), hy-poproteinemia, and anemia, when she was 7 years old. She experienced vomiting and diarrhea after ingestion of egg-coated bread and milk atschool lunch. She was diagnosed with EGE after upper and lower GI endoscopy and biopsies. Modified 6 food-eliminated diets made her symptomsremitted, but she remained unable to eat hen’s eggs and cow’s milk because they induced gastrointestinal symptoms. She also had poor asthmacontrol and started omalizumab, and subsequently mepolizumab. Thereafter, the control of asthma gradually deteriorated, and either omalizumabor mepolibumab were not effective for her asthma but improved gastrointestinal endoscopy and pathological findings. Then she started dupi-lumab, when she was 14 years old. After starting duplimab, asthma control was considerably improved with decreased levels of exhaled nitric ox-ide. EGE was also ameliorated. Peripheral eosinophil count was decreased and oral food challenge test for eggs and milk was negative. Finally, shewas able to discontinue elimination diet. Conclusion: Suppressing of IgE or IL-5 binding signal may improve endoscopic and pathological findingsof EGE and moreover, inhibition of IL-4 and IL-13 signaling induces tolerance to the causative food in gastrointestinal food allergies including EGE.

PE13-14 Exacerbation of an egg allergy induced by an egg-free diet for three years without an increase in food-specific IgE. case report

Shigehito Emura1,2), Saori Takahashi1), Chisato Hori1), Kazuo Takeuchi1), Toshiharu Matsui1), Tetsuki Gunji1) (Department of Pediatrics, NagaokaChuo General Hospital, Japan1); Department of Pediatrics, Niigata Prefectural Shibata Hospital, Japan2))

Background: It has been hypothesised that restriction diets in food-allergic children may induce an increase of food-specific immunoglobulin E(sIgE) levels and the risk of anaphylaxis. The objective of this case report is to highlight an exacerbation of food allergy induced by the eliminationdiet that did not demonstrate an increase in sIgE levels. Case Report: A 14-year-old girl was diagnosed with severe atopic dermatitis and bron-chial asthma. During infancy, she had showed immediate symptoms at ingestion of egg, cow’s milk and wheat, and her egg white-sIgE level wasthen over 100 kUa/L; consequently, she was directed to avoid these foods. At 11-years-old, the patient’s egg white-sIgE level was 11.5 kUa/L andshe ingested half an egg in an oral food challenge (OFC). However, she had avoided ingesting eggs to an egg aversion. At 12-years-old, she was di-rected to avoid egg completely because she had suffered an anaphylactic reaction after ingesting a muffin and then exercising. When the patientwas 14, she was administered with an OFC of half an egg and showed systemic urticaria. Her egg white-sIgE level was 7.58 kUa/L and herovomucoid-sIgE level was 12.0 kUa/L. Conclusion: sIgE levels can remain low over a long-term complete elimination diet, but re-aggravation of afood allergy may still occur upon ingestion of the food.

PE13-15 A case of wild sesame allergy suspected transdermal sensitization

Jun Shirota, Hiroko Sakuma, Fumi Mashiyama, Naoko Suzuki, Yuka Takeda, Hisao Okabe, Eriko Shima (Department of Pediatrics, Hoshi GeneralHospital, Japan)

Introduction: The wild sesame is a member of the perilla family. Its seeds contain alpha-linolenic acid, that an omega-3 fatty acid. It is a healthfood that is expected to be effective in preventing dementia and myocardial infarction, and alleviating allergy symptoms. Fukushima prefecture isknown as a specialty region for growing wild sesame. This time, we report a case of wild sesame allergy. A girl grown in a wild sesame cultivatinghousehold. Case: Patient is a 7-year-old girl with atopic dermatitis. Egg and sesame were removed from her diet because she had a high level ofblood specific IgE. Subsequently, she acquired tolerance for eggs and grain sesame seeds. She had been eating normal school lunch. But when sheate the wild sesame and ground sesame seeds dressing, she experienced itching in mouth, vomiting and facial swelling. We suspected that it wascaused by the wild sesame allergy and conducted an oral food challenge. First, she was able to eat 10 g of ground sesame. Second, she took 0.125 gof wild sesame powder. After thirty minutes, her eyelids were reddened and swelled and became ill. She had never eaten any of the wild sesameand dried plum and shiso leaf. At a later date, the skin-prick test revealed positive for wild sesame powder, and negative for wild sesame oil, shisoleaves and perilla family spices. Conclusion: A case was inferred to be allergic to wild sesame seeds due to transdermal sensitization in a wildsesame-growing household.

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PosterSession

PE13-16 A case of suspected food protein-induced enterocolitis syndrome due to yeast (Saccharomyces cerevisiae )

Koichiro Sato1,2), Hisako Yagi2), Toru Uchida1,2), Mari Tokunaga1), Naoya Arakawa2), Satoshi Yamada2), Yutaka Nishida2), Takumi Takizawa2) (Depart-ment of Pediatrics, Takasaki General Medical Center, Japan1); Department of Pediatrics, Gunma University Graduate School of Medicine, Japan2))

Saccharomyces cerevisiae is a budding yeast widely used for fermentation of bread, wine and beer. There are some cases of systemic symptomssuch as eczema, cough and wheezing as allergy to baker’s yeast, but there are few reports of S. cerevisiae induced food protein-induced enteroco-litis syndrome (FPIES). The case is a 3-year-old girl. When she was 1 year old, she had frequent vomiting approximately 3 hours after ingestingwheat products such as udon and bread. Skin prick test to wheat s was negative, and specific IgE antibodies against wheat, gluten, and ω-5 gli-adin were negative. Oral food charenge (OFC) of 1 g of udon caused frequent vomiting. A non-IgE-dependent wheat allergy was diagnosed. At theage of three, frequent vomiting was observed 5 hours after ingesting homemade rice-flour bread that did not contain wheat but yeast. OFC to thehomemade rice-flour bread caused frequent vomiting in 4 hours.. FPIES to S. cerevisiae was suspected because multiple vomiting occurred 4hours after ingestion. Some cases of the wheat allergies may include S. cerevisiae allergies, which should be taken into account in diagnosis andmanagement of wheat allergy.

PE13-17 Allergic reaction to fish in a patient with no past allergic history

Anna Sargsyan1), Arpine Israelyan2) (Izmirlian MC, Armenia1); Spaulding Rehabilitation Network, USA2))

A girl of 20 years turned to the medical center for help about an allergic reaction. Anamnesis: From the medical history, it was known that 2weeks before going to the clinic, a girl with a friend ate a fish in the restaurant, and after 4 hours, she began a rash on the upper and lower ex-tremities of a reddish hue. The friend with whom she was eating the same fish had no symptoms. Applying to the doctor, she was prescribed anantihistamine medication of the second generation. A week later, the girl returned for a vacation in her country. After the flight, the rash acquireda dark blue hue, the medicine did not help at all. Applying back to the doctor, she was again prescribed an antihistamine medication, already thefirst generation i/v, with 500 ml of a solution of sodium chloride and sodium thiosulfate. For treatment failure, the patient turned to our clinic. Atthe time of the examination, the rash was blue-red, in places with a blackish tint. Other symptoms were swelling and severe itching of the upperand lower extremities. In the past, the patient never had any allergic reactions, nor was there anyone with any allergic manifestations in the fam-ily. The patient noted that she always eats a lot of different seafood and there has never even been discomfort. We could not find anything else toassociate with the cross-reaction. All lab tests were in norma, allergy tests for common foods were negative. Treatment: In the treatment, we pro-ceeded from the symptoms of developed vasculitis and suggested a reaction to the toxin, presumably present in the part of the fish that the pa-tient ate. Treatment was prescribed including a third-generation antihistamine, phlebotonic medications, a topical non-steroid anti-inflammatorydrug, and topical anticoagulant. On the fourth day of treatment, the symptoms decreased significantly, the rash almost disappeared. The patientfully recovered after 10 days.

PE13-18 A case series of solid food protein-induced enterocolitis syndrome

Mai Tokunaga, Yumi Koike (Department of Allergy, Nagano Children’s Hospital, Japan)

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE)-mediated food allergy. Although milk is themain trigger during neonatalinfant phases, cases of solid food allergies, referred to as solid FPIES, appear after the weaning phase at an increas-ing rate. In solid FPIES, symptoms can take hours to develop, and causal antigens differ from those of more immediate allergic reactions. Thisoften leads to an overlooked diagnosis. There have been relatively few reports of FPIES caused by solid foods in Japan. Additionally, its manage-ment method, including food intolerance tests, has not been established. Objective: To assess the clinical features and course of solid FPIES in ourhospital. Method:We conducted a retrospective study designed to investigate patients who were diagnosed with solid FPIES between January2017 and September 2019. We diagnosed FPIES in case of vomiting in the 1 to 4 hour period after ingestion of the suspect food and absence ofclassic IgE-mediated allergic skin or respiratory symptoms. Results: Twelve patients were diagnosed with solid FPIES during the study period.The median age at onset was 9 months, and the median age at diagnosis was 15 months. The causative foods were egg white (2 patients), egg yolk(6), wheat (1), soy (2), and whitebait (1). The symptoms included recurrent vomiting in 11 patients and vomiting with diarrhea in 1 patient. Eightpatients tested negative for specific IgE, while 4 tested positive. Oral food challenges (OFCs) were performed for 7 patients to diagnose or confirmtolerance. The median age at the OFC was 1 year and 8 months, and the median time of the OFC was 13 months from onset; 5 of 7 patients (71%)tested positive. As of September 2019, 2 patients had remission. Conclusion: Egg yolk was a common cause of solid FPIES at our hospital. A highrate of positive OFCs was observed approximately 1 year after onset. Solid FPIES has been reported with various courses; hence, further studiesinvolving a greater number of patients are needed.

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PosterSession

PE13-19 Generalized allergic reaction caused by strawberry gibberellin-regulated protein: a case report

Chisato Inuo1), Fumiko Okazaki2), Risa Shiraki2), Keiko Momma3), Hiroshi Narita4) (Department of Allergy, Kanagawa Children’s Medical Center, Ja-pan1); Department of Food Science and Human Nutrition Faculty of Agriculture, Ryukoku University, Japan2); Department of Food Science, KyotoWomen’s University, Japan3); Kyoto College of Nutritional and Medical Sciences, Japan4))

Background: In recent years, gibberellin-regulated protein (GRP) has been identified as a new allergen that induces generalized symptoms in or-ange, Japanese plum, and peach allergy. However, there is no report of generalized allergic symptoms induced by strawberries, which are culti-vated and consumed worldwide. Here, we report the identification of GRP as a new allergen in exercise-induced strawberry allergy. Case presen-tation: A 15-year-old boy had experienced episodes of generalized urticaria induced by exercise after ingestion of strawberries. Although a con-firmed diagnosis of strawberry allergy was made with the food challenge test, the strawberry specific-immunoglobulin (Ig) E level in Immuno-CAP was normal. His specific IgE level for Japanese cedar pollen was 26.4 UA/mL and that for Japanese cypress pollen was 9.73 UA/mL,whereas those for birch, Alder pollen, and rBet v 1 were normal. The skin prick test using strawberry yielded positive result. Method: NaturalGRP was purified from strawberry crude extract by an immunoaffinity column using a monoclonal antibody against peach GRP, which exhibitedcross-reactivity to strawberry. IgE specific to GRP in strawberry was measured by enzyme-linked immunosorbent assay (ELISA) withperoxidase-labelled anti-human IgE. Result: Purified strawberry GRP yielded a single band on SDS-PAGE with a molecular size of approximately12 kDa. The patient’s serum was reacted with the strawberry GRP on ELISA. Conclusion: To the best of our knowledge, this is the first case re-port of generalized allergic symptoms induced by consumption of strawberries. Our findings indicated that GRP is the causative allergen of gen-eralized symptoms induced by strawberry.

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PosterSession

Poster Session 14Clinical immunology

PE14-1 A child case of recurrent hypereosinophilia caused by Streptococcus pyogenes infection

Junya Abe, Hiroshi Numata, Kenji Nakagawa, Takakazu Yoshioka, Mitsutaka Shiota, Daisuke Hata (Department of Pediatrics, Kitano Hospital,Tazuke Kofukai Medical Research Institute, Japan)

Background: Hypereosinophilia (HE) is defined as an absolute eosinophil count of >1.5×109/L measured on at least two occasions with an intervalof 1 month and/or histologically-proven tissue infiltration by eosinophils. HE is most common in adults aged 2050 years and parasitic infections area major cause of HE. Case Presentation: At the age of 3 years, eosinophil count of a Japanese girl increased to 4×109/L, although the detailedclinical course was unknown. At the age of 9 years, she suffered from occasional mild abdominal pains. Laboratory tests revealed increasedeosinophil count and increased levels of anti-streptolysin O (ASO) antibodies. Serum total IgE and wheat- and gluten-specific IgE antibody levelswere also high. Although she received antibiotic agents and antihistamine and removed wheat from her diet, the eosinophil counts increased to >10×109/L. There was no evidence of parasitic infections or malignancy. A lower gastrointestinal endoscopy showed no obvious abnormalities.However, biopsies revealed eosinophil infiltration of the mucosal layers of the ascending and descending colon, which could satisfy the diagnosticcriteria for eosinophilic gastroenteritis (EGE). Since eosinophil infiltration did not increase to a greater level, and there was no obvious evidence oforgan damage, we could not attribute her abdominal symptoms unequivocally to EGE. She did not receive steroids because her symptoms weremild. Later, the eosinophil counts were decreasing gradually to < 0.5×109/L. At the age of 10 years, she suffered from a fever and occasional mildabdominal pains. She was diagnosed with Streptococcus pyogenes (Group A Streptococcus; GAS) pharyngitis since a rapid antigen test was posi-tive and received other antibiotic agents. Eosinophil counts increased gradually to >10×109/L over 2 months and fell gradually without steroids.Discussion: GAS infection is a common disease in children and can cause HE, although a detailed mechanism of GAS-induced HE is unknown. Shewas diagnosed with a recurrent HE caused by GAS infection since elevated eosinophil counts were strongly associated with increased ASO.

PE14-2 Multiple hepatic aneurysm and dry gangrene of fingertips in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Eunsil Koh1), Dong-Chull Choi1), Byung-Jae Lee1), Young-soo Do2), Duk-Kyung Kim1), Jin-Young Lee3), Noeul Kang1), Jae-Won Jeong4),Sang-Hoon Kim5) (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea1); Depart-ment of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea2); Health Promotion Center, Sam-sung Medical Center, Republic of Korea3); Department of Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Republic of Korea4);Department of Medicine, Eulji General Hospital, Eulji University School of Medicine, Republic of Korea5))

Rationale: As EGPA is a systemic necrotizing vasculitis mainly affecting small-sized arteries, clinical features of medium-sized vasculitis wasvery rare in EGPA. Here we present that multiple hepatic aneurysms and distal gangrene presented in the same patient with EGPA. Methods:The angiography was performed because of hepatic subcapsular hematoma. Results: The patient treated for EGPA presented to the emergencyroom with abrupt squeezing abdominal pain. She have experienced sudden onset of gangrene in both fingertips one year ago because of arterialthrombosis when her eosinophil count increased up to 6,000cells/µL. Her absolute eosinophil count in ER was 1,120cells/µL. The abdomen_pelvisCT demonstrated hepatic subcapsular hematoma in right lobe caused by suspicious aneurysmal rupture. We immediately performed angiogra-phy. The celiac angiogram demonstrated multiple sized hepatic aneurysms in both lobe and some of aneurysm in S7 and S8 were huge, evenmore than 1 cm. The appearance of small aneurysms was string of beads, generally observed in polyarteritis nodosa. Given the clinical situations,the emergency embolization was done. This patient has been treated with relatively high dose steroid, azathioprine and cyclophosphamide. Aftermepolizumab started, eosinophil count showed stable state with near zero percentage. Conclusion: Small aneurysm and gangrene can occur inEGPA. Deconstruction of vessel associated with vasculitis can be active when eosinophil count is even below 1,500cells/µL. If medium sized arter-ies is suspected to be involved in EPGA with distal ischemia, thorough control of eosinophilia with several immunosuppression might be neededto prevent from the fatal complication.

PE14-3 Presence of purpura as an important clinical index for high disease activity with increased serum IL-5 in eosinophilic granuloma-tosis with polyangiitis

Hiroshi Kataoka, Masaya Mukai (Department of Rheumatology and Clinical Immunology, Sapporo City General Hospital, Japan)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a relatively rare necrotizing vasculitis with eosinophil infiltration driven byIL-5. Anti-IL-5 monoclonal antibody has been applied to relapsing EGPA, but it remains unknown which clinical symptom reflects increased IL-5.Methods: Patients of EGPA were searched in our electric records by the disease name for recent 10 years. Diagnosis of EGPA was reconfirmedaccording to the American College of Rheumatology 1990 Criteria based on their records that were required for the diagnosis. Symptoms at theonset of EGPA, changes in laboratory parameters (eosinophil count, CRP, IgE and IL-5) during treatment, initial and recent dose of prednisolone,history of additional use of immunosuppressants were compared among eligible cases. This was a retrospective observation study approved bythe ethical committee of our hospital (H30-059-515). Results: A total of 28 EGPA patients (21 females and 7 males) were eligible for this study. Av-erage age was 59 (female) and 52 (male) and average disease duration was 3.6 years (female) and 2.6 years (male). Almost all patients (91% femaleand all male) developed peripheral nerve disorder. Fever occurred in 28% (female) and 16.7% (male), nasal symptom in 27% (female) and 66.7%(male) and, cutaneous lesions (all purpura) in 50% (female) and 28.6% (male). 5.3% of female and 14.3% of male patients showed renal involvement.Their laboratory data revealed a marked increase in peripheral eosinophil count (10639±9615/L), elevated CRP (4.2±3.2mg/dl), serum IgE (1514±1358ng/ml) and serum IL-5 (94.1±101.1pg/ml). 15.4% of the patients showed positive ANCA (75% MPO-ANCA, 25% PR3-ANCA). Initial CRPcorrelated to serum IL-5 and IgE (r2=0.63 (p=0.0006), 0.16 (p=0.039), respectively). At the diagnosis of EGPA, presence of purpura was relevant toelevated CRP as compared with absence of them (6.2±2.7 vs 3.2±2.8 mg/dl, p=0.022) and serum IL-5 (155.8±103.1 vs 50±78.8, p=0.0303) and highBVAS score (14±4 vs 9±4, p<0.01)(presence vs absence). Conclusions: Presence of purpura is an important symptom indicating high disease ac-tivity of EGPA with elevated IL-5.

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PosterSession

PE14-4 Elevated serum levels of galectin-10 in active eosinophilic granulomatosis with polyangiitis

Yosuke Kamide1), Shigeharu Ueki2), Mineyo Fukuchi2), Norihiro Fujita1), Maki Iwata1), Kisako Nagayama1), Yuto Nakamura1), Koichi Yano1),Kentaro Watai1), Yuto Hamada1), Kai Ryu1), Hiroaki Hayashi1), Yuma Fukutomi1), Kiyoshi Sekiya1), Akio Mori1), Masami Taniguchi1,3) (Clinical Re-search Center for Allergy and Rheumatology, Sagamihara National Hospital, Japan1); Department of General Internal Medicine and Clinical Labo-ratory Medicine, Akita University Graduate School of Medicine, Japan2); Shonan Kamakura General Hospital Center for Immunology and Aller-gology, Japan3))

Background: Galectin-10 (Gal-10) is one of the most abundant proteins in eosinophils and is released from activated eosinophils. Charcot-leydencrystals (CLCs) are composed of Gal-10 and are known to induce type 2 inflammation in the airway mucosa. In the present study, we determinedof Gal-10 in serum of eosinophilic granulomatosis with polyangiitis (EGPA) patients.Methods: Gal-10 was measured in sera of 15 patients with ac-tive EGPA, 15 patients with remission EGPA and 15 healthy subjects by ELISA. Active EGPA was characterized by increased eosinophil counts(> 10% eosinophils or > 1000 eosinophils/l) and active vasculitis in at least one organ. To evaluate the relationship between Gal-10 and bloodeosinophil density, Gal-10 was normalized to divided by blood eosinophil count. Results: Gal-10 levels (median and interquartile range ng/ml) wassignificantly elevated in active EGPA (28.64 (6.860-38.74)) as compared with remission EGPA (0.00 (0.00-0.940)) and healthy subjects (0.00 (0.00-0.00)).Similarly, normalized galectin-10 was significantly elevated in active EGPA. Conclusion: We detected that Gal-10 levels was increased in sera ofactive EGPA.

PE14-5 Oligoclonal expansion of circulating Tph cells is related to the pathogenesis of IgG4-related disease

Hayato Yabe1,2), Ryuta Kamekura1,3), Motohisa Yamamoto4), Hirofumi Chiba2), Hiroki Takahashi4), Kenichi Takano3), Hiroki Takahashi2),Shingo Ichimiya1) (Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine,Japan1); Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Japan2); Department of Otolaryn-gology, Sapporo Medical University School of Medicine, Japan3); Department of Rheumatology and Clinical Immunology, Sapporo Medical Univer-sity School of Medicine, Japan4))

Background: IgG4-related disease (IgG4-RD) is a chronic inflammatory disease characterized by elevated serum IgG4, infiltration of IgG4-positiveplasma cells, and fibrosis of affected organs. However, the underlying immunological mechanisms involved in IgG4-RD remain unknown. We pre-viously reported that CD4+ T cell subsets such as follicular helper T cells and follicular regulatory T cells play an important role in the patho-genesis of IgG4-RD (J Immunol. 2017, Immunol Lett. 2019). In this study, we examined peripheral helper T (Tph) cells which are a new CD4+ Tcell subset in IgG4-RD.Methods: Tph (PD-1hiCXCR5-CD4+) cells from patients with IgG4-RD and healthy controls were analyzed by flow cytome-try. Correlations between results obtained by flow cytometry and clinical parameters related to IgG4-RD were analyzed. Sorted Tph cells wereanalyzed by real-time PCR and T cell receptor (TCR) repertoire analysis. Results: Percentage and absolute number of circulating Tph cells wereincreased in patients with IgG4-RD compared to controls, and the percentage of Tph cells was positively correlated with clinical parameters suchas serum IgG4 and the number of affected organs. Interestingly, granzyme A+ cells were enriched in Tph cells, and the percentage and numberof granzyme A+ Tph cells were significantly elevated in IgG4-RD patients. Furthermore, Tph cells from patients with IgG4-RD had lower diver-sity of TCR repertoire than those from healthy controls. Conclusion: These results suggest that oligoclonally expanded Tph cells in IgG4-RD havecytotoxic potential. They are thought to be memory T cells which recognize specific foreign antigens. Further analysis of cytotoxic Tph cells maylead to a deeper understanding of the pathogenesis of persistent inflammation in IgG4-RD.

PE14-6 Predictive factors of the therapeutic response to mepolizumab in patients with eosinophilic granulomatosis with polyangiitis

Takami Kobayashi1), Hiroaki Tsurumaki1), Yuji Onuki1), Haruka Aoki-Saito1), Yasuhiko Koga1), Makiko Sato1), Masakiyo Yatomi1), Asuka Jingu1),Koichi Yamaguchi1), Kenichiro Hara1), Noriaki Sunaga1), Toshitaka Maeno1), Takeshi Hisada2) (Department of Respiratory Medicine, Gunma Univer-sity Graduate School of Medicine, Japan1); Gunma University, Faculty of Medicine School of Health Sciences, Japan2))

Background: The administration of mepolizumab reduces the relapse of eosinophilic granulomatosis with polyangiitis (EGPA) and maintenancedose of oral corticosteroids (OCSs) for EGPA. The predictive factors of the therapeutic response to mepolizumab in patients with EGPA remainunknown. Accordingly, we explored these predictive factors in this study. Methods: The clinical information of patients with EGPA who weretreated in Gunma University Hospital between April 2015 and March 2020 was collected retrospectively. Seventeen patients were included, andclinical data including clinical characteristics, comorbidities, laboratory findings, lung function test findings, and treatment information were col-lected. All procedures performed in this study involving human participants were in accordance with the Gunma University Hospital clinical re-search review board. Results: The median age of the patients was 55.8 years. The proportion of male patients was 47.1%. The rates of comorbidi-ties were 94.1%, 41.1%, and 41.1% for bronchial asthma, allergic rhinitis, and eosinophilic chronic rhinosinusitis, respectively. The counts of eosino-phils in peripheral blood at the time of diagnosis were 10268±11228 cells/µL (mean±standard deviation). The titer of immunoglobulin E (IgE)was 1883±2559 IU/mL, while that of myeloperoxidase antineutrophil cytoplasmic antibody was 71±133 U/mL. The ratio of forced expiratoryvolume in one second, and forced vital capacity was 75.4±9.6%. Mepolizumab was administered in 9 cases (52%). In 6 of 9 cases, eosinophil countsand IgE levels decreased, and the OCS dose was reduced with the administration of mepolizumab for 6 months; however, it was impossible to re-duce the OCS dose in 3 cases. The count of eosinophils before the administration of mepolizumab was lower in the group in which the OCS dosecould not be reduced than in the group in which the OCS dose could be reduced. Conclusion: The count of eosinophils before the administrationof mepolizumab may be a predictive factor for the response to treatment in patients with EGPA.

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PosterSession

PE14-7 Effects and mechanisms of IVIG on the inflammatory response of a cultured human coronary artery endothelial cell model ofKawasaki disease

Takashi Inoue1,2), Shokei Murakami1), Kenji Matsumoto1), Akio Matsuda1) (Department of Allergy and Clinical Immunology, National Research In-stitute for Child Health and Development, Japan1); Department of Pediatrics, Jikei University School of Medicine, Japan2))

Background: Kawasaki disease (KD) is the most common pediatric vasculitides of unknown etiology, and the morbidity rate of KD in Japan hascontinued to rise. Intravenous immunoglobulin (IVIG) has been used as the first-line standard treatment for KD and is highly effective in almost80% of patients. However, the remaining patients are resistant to initial IVIG treatment, and they are at high risk for coronary artery lesions.IVIG, a biological preparation, contains polyvalent IgG purified from human blood for treatment of various immune diseases, including KD. Westill do not understand why IVIG treatment is useful for the vast majority of KD patients or the mechanisms by which some patients developIVIG resistance. We aimed to shed light on those issues by using cultured primary human coronary artery endothelial cells (HCAECs) as an in vi-tro model of KD. Methods: Cultured HCAECs were stimulated with TNF-α, IL-1β and IL-17A, alone or in combination, in the presence and ab-sence of 10 mg/ml IVIG for 48 hours. The mRNA levels (by qPCR) and protein concentrations (by ELISA) of IL-6 and G-CSF were measured. Nu-clear extracts of HCAECs were prepared, and the expression (Western blotting) and activity (EMSA assay) of transcription factors C/EBPβ andC/EBPδ were analyzed. Results: The IVIG treatment completely suppressed the mRNA and protein levels of IL-6 and G-CSF induced inHCAECs by TNF-α alone due to decreases in the expression and activities of the C/EBPs. On the other hand, IVIG was unable to suppress theexpression and activities of the C/EBPs when IL-1β or IL-17A was added to TNF, resulting in IVIG-resistant production of IL-6 and G-CSF bythe HCAECs. Conclusion: Nuclear transcription factors C/EBPβ and C/EBPδ were crucially involved in the anti-inflammatory effects of IVIGon the cultured HCAECs. IL-1β and IL-17A cytokines triggered IVIG resistance in this model. Thus, C/EBPs may be important drug treatmenttargets for preventing coronary artery lesions in patients with IVIG-resistant KD.

PE14-8 Changes of MMP-9 and MMP12 in response of acute viral infection in virtual model of macrophages

Junehyuk Lee, Aerin Baek, Joohyun Park, Sung-Woo Park, Do-Jin Kim, An-Soo Jang (Respiratory and Allergy, Soonchunhyang Universiy Bu-cheon Hospital, Republic of Korea)

Background:Macrophages are known to contribute an important role in the balance of extracellular homeostasis. MMP-12 is mainly produced bymacrophages and has protective effects such as anti-tumorigenic, anti-inflammatory and antibacterial activities. MMP-9 is an important compo-nent that involved in mechanism of fibrosis. We already presented virtual model between M1 and M2 macrophages after viral infection. We triedto predict the responses of MMP-9 and MMP-12 after acute viral infection using this model. Methods: MMP-9 and MMP-12 were added in themodel along with their parameters. Baseline conditions were selected from literatures and parameters were estimated. Simulations were per-formed with changing the time and intensity of infection. Asthmatic condition was experimented with changing IFN-b and IL-4 producing rate.Results:MMP-12 showed higher peak and longer duration of increase in response to more viral load. MMP-12 also showed longer duration of in-crease in response to longer duration of viral infection. While, changes of MMP-9 were less than that of MMP-12 in both experiments of intensityand duration of infection. There were a few changes in both MMPs between normal and asthma-like condition. Conclusions:We could predict al-terations of MMP-9 and MMP-12 in acute stage of viral infection, which there has not been experimental data. Further modifications of model arerequired to add factors of neutrophils or inhibition.

PE14-9 A novel self-pay newborn screening program for severe combined immunodeficiency in Japan

Yuzaburo Inoue1,13), Toru Uchiyama2,13), Masafumi Onodera2,13), Masafumi Yamada3,13), Joo-Hyun Seo4,13), Motomichi Kosuga4,5,13), Ohsuke Migita6,13),Toju Tanaka7,13), Takuya Fushimi8,13), Kei Murayama8,13), Hiroshi Mochizuki9,13), Torayuki Okuyama4,10,13), Masaki Takayanagi11,13), Akira Ohtake12,13)

(Department of Allergy and Rheumatology, Chiba Children’s Hospital, Japan1); Department of Human Genetics, National Center for Child Healthand Development, Japan2); Department of Pediatrics, Hokkaiodo University Graduate School of Medicine, Japan3); Clinical Laboratory Medicine,National Center for Child Health and Development, Japan4); Division of Medical Genetics, National Center for Child Health and Development, Ja-pan5); Department of Pediatrics, St Marianna University School of Medicine, Japan6); Center for Genetics & Metabolic Disorder and Clinical Re-search, National Hospital Organization Hokkaido Medical Center, Japan7); Center for Medical Genetics, Department of Metabolism, Chiba Chil-dren’s Hospital, Japan8); Department of Metabolic Endocrinology, Saitama Children’s Medical Center, Japan9); Center of Lysosomal Storage Dis-eases, National Center for Child Health and Development, Japan10); Department of Physical Therapy, Faculty of Health Care and Medical Sports,Teikyo Heisei University, Japan11); Department of Pediatrics & Clinical Genomics, Faculty of Medicine, Saitama Medical University, Japan12); Clini-cal & Research Association for Rare, Intractable Diseases, Japan13))

Background: Severe combined immunodeficiency (SCID) is a fatal syndrome of diverse genetic causes characterized by a profound deficiency offunctional T cells. As SCID causes life-threatening infections, early diagnosis of SCID is essential, and hematopoietic stem cell transplantationshould be performed before getting infections. In the USA, SCID is one of the diseases which is listed in the Recommended Uniform ScreeningPanel in the USA. However, there is no public funding for newborn screening (NBS) programs for SCID in Japan. Method: We began a self-payNBS program for SCID in April 2019. T-cell receptor excision circles (TRECs) in dried blood spot samples were quantified with the Enlite Neona-tal TREC kitⓇ. Results: During 11 months, we screened 9634 samples from 21 OB/GYN clinics. The detection cutoff was updated based on the ex-perience gained in the first four months and changed from 30 to 20 copies/µL. This decreased the positive detection rate from 0.44 to 0.027%. Dur-ing the period, no patient was diagnosed with SCID, and other patients were considered false-positive cases. Conclusion: We successfullylaunched a self-pay NBS program for SCID in Japan. Further adjustment of the detection cutoff would be needed to decrease burdens of follow-upon medical institutions and the anxiety of guardians.

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PosterSession

PE14-11 Immunologic analysis on children with post-infectious bronchiolitis obliterans

Yun Jung Choi, Jihye Kim, Minjung Kim, Ji Soo Park, Minjin Jeon, Soyoung Lee, Dong In Suh (Department of Pediatrics, Seoul National UniversityHospital, Republic of Korea)

Purpose: Postinfectious bronchiolitis obliterans (PIBO) is a rare and severe chronic lung disease resulting after lower respiratory tract infectionduring childhood, especially early childhood. The pathogenesis of PIBO has not been fully elucidated. In particular, little is known about the hostimmunologic risk factors associated with development of PIBO.Methods: The subjects aged under 18 years, with a diagnosis of PIBO confirmedby chest computed tomography were enrolled. Immunologic profiles were evaluated, immunoglobulins level and lymphocyte subset were meas-ured. Peripheral blood mononuclear cell obtained from subject’s lymphocyte were analyzed using flow cytometry (FACS) to identify abnormalcells by defining their immunophenotypic characteristics. Results: Total 9 cases were enrolled. Four patient (44.4%) had past history of myco-plasma pneumonia, and 3 cases (33.3%) had been infected with Respiratory syncytial virus. Immunoglobulin levels in all patients were within thenormal reference range. Subject’s flow cytometric analysis did not showed significant different frequencies of B-cell or T-cell subset comparedwith normal data : (1) subtype analysis according to IgD, CD27, CD38, and CD24 expression in CD19 + B cells present in peripheral blood; Nave,Memory, Regulatory, Plasma cells (2) subtype analysis according to CCR7, CD45RA, IL-7Rα expression in CD4 + or CD8 + T cells: Nave, CentralMemory, Effector Memory cell (3) subtype analysis according to CCR6 and CXCR3 expression in CD4 + CXCR5 + CD45RA-Tfh cells: Tfh1, Tfh2and Tfh17 cells (4) subtype analysis according to CD25 and Foxp3 expression in CD4 + T cells: Regulatory T cell. Conclusion: Although no char-acteristic systemic immune function abnormality was found in the PIBO patient group, immunologic work up to find the host factor is an impor-tant area. In the future, further studies are needed to find out systemic and focal immunologic cause of PIBO.

PE14-12 Clinical characteristics of macrolide-refractory mycoplasma pneumoniae pneumonia in Korean children: multicenter retrospec-tive cohort study

Yun Jung Choi1), Minjung Kim1), Dong In Suh1), Hyeon-Jong Yang2,3), Pneumonia and Respiratory Disease Study Group4) (Department of Pediatrics,Seoul National University Hospital, Republic of Korea1); SCH Biomedical Informatics Research Unit, Soonchunhyang University Seoul Hospital,Republic of Korea2); Department of Pediatrics, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Repub-lic of Korea3); Korean Academy of Pediatric Allergy and Respiratory Disease, Republic of Korea4))

Purpose: Macrolide-refractory Mycoplasma Pneumoniae pneumonia (MRMP) has rapidly increased in Asia. The increment of MRMP raised sig-nificant public health concern due to the limited early diagnosis and alternative therapies in children. Methods: We constructed a mycoplasmapneumonia (MP) retrospective cohort database from 22 secondary and tertiary hospitals (Pneumonia & Respiratory diseases Study Group of KA-PARD). The inclusion criteria were; (1) hospitalized children (18 years) with mycoplasma pneumonia during January 1, 2009 to December 31, 2015;(2) a 4-fold or greater increase in IgM and/or IgG antibody titers between acute and convalescent stage. The MP participants were extracted anddivided into three groups; MRMP (7 days), macrolide-less effective MP (MLMP, 3-7 days), and macrolide-sensitive MP (MSMP) according to the fe-ver duration after use of macrolide. Results: Total of 9,205 MP cases were enrolled, 7,469 cases were analyzed; MRMP (n=391, 5.2%), MLMP (n=1,305, 17.5%), and MSMP (n=5773, 77.3%). MRMP group showed significantly longer length of stay, more frequent dyspnea, cyanosis, oxygen satu-ration <90%, and oxygen therapy, and more severe radiological findings (atelectasis, pleural effusion, and lobar consolidation) than MLMP andMSMP (all of p<0.01). MRMP showed significantly higher initial C-reactive protein (CRP), lactate dehydrogenase (LDH) and AST (p<0.01). Amongextrapulmonary symptoms, rash, erythema multiforme and proteinuria were more accompanied with MRMP group than MLMP, MSMP groupand postinfectious sequelae such as atelectasis, postinfectious bronchiolitis obliterans were also more common in MRMP group (all of p<0.01). Inpre-existing conditions, malignancy and neurological disease were more common in MRMP (p<0.01). Otherwise, asthma was more common inMSMP. Congenital heart diseases and bronchopulmonary dysplasia did not show statistical significance among MP groups. There were no labora-tory and clinical characteristic differences between MP groups and MP with viral infection group. Conclusion: The present results provide im-portant clinical features that can be used to distinguish MRMP in the early stage. However, these results may be biased by initial severity due tothe inherent limitation of retrospective design. Further prospective study will be necessary.

PE14-13 Oral once-daily berotralstat (BCX7353) reduces hereditary angioedema (HAE) events and is well-tolerated: pivotal phase 3 study(APeX-J) results from Japan

Isao Ohsawa1), Daisuke Honda2), Yusuke Suzuki3), Tomoo Fukuda4), Keisuke Koga5), Eishin Morita6), Shinichi Moriwaki7), Osamu Ishikawa8),Tomoe Kobayashi9), Yoshihiro Sasaki10), Masaki Tago11), Greg Chittick12), Sharon Murray12), Sylvia Dobo12), Eniko Nagy12), Sharon Van Dyke12),Lacy Reese12), Phil Collis12), William Sheridan12), Michihiro Hide13) (Department of Nephrology, Saiyu Soka Hospital, Japan1); Juntendo UniversityUrayasu Hospital, Japan2); Juntendo University Hospital, Japan3); Saitama Medical Center, Japan4); Community Hospital Koga Hospital, Japan5);Shimane University Hospital, Japan6); Osaka Medical College Hospital, Japan7); Gunma University Hospital, Japan8); Tomakomai City Hospital, Ja-pan9); National Hospital Organization Disaster Medical Center, Japan10); Saga University Hospital, Japan11); BioCryst Pharmaceuticals, USA12); Hi-roshima University, Japan13))

Background: Berotralstat is the first orally-administered, once-daily, highly-selective plasma kallikrein inhibitor shown to reduce angioedemaevents in a phase 3, double-blind, placebo-controlled study (APeX-2) in Europe and North America. Here we present results from a phase 3 studyin Japan (APeX-J; UMIN000034869). Methods: Patients with type 1 or 2 HAE with 2 expert-confirmed angioedema events in 8 weeks were ran-domized to berotralstat 150 or 110mg or placebo (1:1:1) once-daily for 24 weeks (Part 1), stratified by baseline event rate (<2, 2/month). At Week24, patients randomized to berotralstat continued on treatment while placebo recipients were re-randomized (1:1) to berotralstat 150 or 110mgthrough Week 52 (Part 2). The primary endpoint was the expert-confirmed angioedema event rate through Week 24. Results: Nineteen patients(84% female, 95% Asian, 47% with 2 expert-confirmed events/month) were randomized to 150mg (n=7), 110mg (n=6), or placebo (n=6). The 150and 110mg berotralstat doses reduced expert-confirmed event rates by 49% (p=0.003) and 25% (p=0.181), respectively, vs. placebo. In the 150mggroup, 57% of patients had 50% reduction and 29% had 70% reduction in adjusted event rate relative to baseline vs. 0% placebo patients. The dif-ference in least squares means (LSM) for the proportion of days with angioedema symptoms vs. placebo was -0.12 (p=0.120) for the 150mg group,representing ～20 more symptom-free days over 24 weeks. The LSM difference in angioedema quality-of-life questionnaire total scores at Week24 was 19.0 (p=0.061) in favor of berotralstat 150mg vs. placebo. All berotralstat-treated patients completed through Week 24, with no treatment-related SAEs or Grade 3/4 events; reported AEs were generally mild and self-limiting. Conclusion: Oral once-daily berotralstat was effective insuppressing angioedema events and was safe and generally well-tolerated in HAE patients in Japan.

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PosterSession

PE14-16 Diagnostic criteria for proteasome-associated autoinflammatory syndromes (PRAASs) including Nakajo-Nishimura syndrome,JMP syndrome and CANDLE syndrome

Nobuo Kanazawa1), Hiroaki Ida2), Noriko Kinjo3), Tomoaki Ishikawa4), Ryuta Nishikomori5) (Department of Dermatology, Wakayama Medical Uni-versity, Japan1); Department of Medicine, Division of Respirology, Neurology, and Rheumatology, Kurume University Faculty of Medicine, Japan2);Department of Pediatrics, University of the Ryukyus Graduate School of Medicine, Japan3); Department of Pediatrics, Nara Medical University, Ja-pan4); Department of Pediatrics, Kurume University Faculty of Medicine, Japan5))

Nakajo-Nishimura syndrome (NNS) was originally described in Japanese by Nakajo in 1939 and by Nishimura in 1950, and then reported in Eng-lish as“a syndrome with nodular erythema, elongated and thickened fingers, and emaciation”in 1985 and as“hereditary lipo-muscular atrophywith joint contracture, skin eruptions and hyper-γ-globulinemia”in 1993. It was in 2011 that similar syndromes have first been reported fromoutside Japan, which included“joint contractures, muscular atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP)”syndromeand“chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperature (CANDLE)”syndrome. As PSMB8 mutations havecommonly been identified in NNS and these two syndromes, they are collectively called as“proteasome-associated autoinflammatory syndromes(PRAASs)”. Recently, their responsible genes are expanding to other proteasomal genes. Although NNS has been defined as an officially regis-tered intractable disease with distinct diagnostic criteria in Japan, no global diagnostic criteria for PRAASs have been determined. Therefore, sofar reported 30 NNS, 3 JMP and 21 CANDLE/PRAAS cases have been reviewed and the diagnostic criteria of NNS have been verified for thesecases. For the original criteria in which more than 5 are required among 8 clinically characteristic points, only 80% of NNS, 100% of JMP and 67%of CANDLE/PRAAS cases meet the criteria, while most of NNS cases reported before 1990 and CANDLE/PRAAS cases without any descriptionon pernio-like rash do not meet. If one point“hepatosplenomegaly”is changed to“hepatomegaly”and 2 points of“microcytic anemia”and

“hyper-γ-globulinemia”are added to the points and more than 6 of the final 10 points are required for the diagnosis, positivity of the new criteriareaches 93% of NNS, 100% of JMP and 76% of CANDLE/PRAAS cases. In conclusion, a new diagnostic criteria for PRAASs have been proposed:clinically, at least 6 points are required among newly-defined 10 points, and genetically,“definite”when disease-associated proteasomal gene mu-tation(s) are identified and“probable”even if such mutation(s) are not identified, but when other diseases are differentiated.

PE14-17 The clinical effects of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis

Yasuhiro Hasegawa, Yoshiyuki Arinuma, Kunihiro Yamaoka (Department of Rheumatology and Infectious Diseases, Kitasato University, Japan)

Purpose: The aim of this study is to investigate the clinical effects of mepolizumab (MEP) in patients with eosinophilic granulomatosis with poly-angiitis (EGPA). Patients and Methods:We collected EGPA patients during the maintenance therapy who had been treated at Kitasato Univer-sity Hospital. We analyzed changes of the disease activity and the corticosteroids dose from February 1, 2020, to May 30, 2020, retrospectively. Re-sults: Twenty-nine EGPA patients were recruited in this study, and MEP had been used for more than 3 months in 12 of 29 patients (MEP group).MEP was introduced in 7 patients due to exacerbation of disease activity during PSL-tapering, and in 5 patients for remission induction therapy.Cyclophosphamide had been introduced in 6 patients (50.0%) of MEP group and in 6 patients (35.3%) who had not received MEP (non-MEP group).ANCA was detected in 6 of 12 patients (50.0%) in MEP group and 9 of 17 patients (41.2%) in non-MEP group. There was no difference in the initialdaily prednisolone (PSL) dose between MEP group and non-MEP group (p=0.622). The median daily PSL dose significantly decreased (5 [0-18] mg/day to 4 [0-12] mg/day (p=0.004)) in MEP group, but not in non-MEP group (5 [0-10] mg/day to 5 [0-10] mg/day (p=0.500)). Nine patients (52.9%) innon-MEP group had been receiving PSL without tapering. Definitive eosinophilia (eosinophil count >500 cells/L or white blood cell count >5%)was not observed in MEP group but 4 patients (23.5%) in non-MEP group had sustained eosinophilia. The ANCA positivity or cyclophosphamideuse did not contribute to tapering PSL and improving eosinophilia. Conclusion:MEP can be useful for tapering the daily PSL dose with maintain-ing low disease activity in patients with EGPA, no matter if MEP was initiated for remission induction or maintenance therapy.

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PosterSession

Poster Session 15Drug hypersensitivity

PE15-1 First recombinant factor IX extended-infusion desensitization protocol in Mexico and Latin-America

Raul Alberto Montero (Pediatric Allergy & Immunology, Instituto Nacional de Pediatría, Mexico)

Background: Hemophilia B patients who manifest allergic reactions to plasma products and high-title levels of inhibitors need to be inducted todesensitization and immune tolerance induction protocols. This is the first report of an immune tolerance induction ever done in Mexico and LatinAmerica.Methods:We designed our procedure based on a 16 steps protocol to a year and a half year old patient with hemophilia B severe IX de-ficiency (0.7%), high response inhibitors (42.2 BU), and an anaphylactic reaction who haven’t had an optimal response to prophylaxis despite theuse of recombinant Factor IX and VII. Hydrocortisone, Diphenhydramine, Ranitidine and Acetaminophen 60 min prior the first dose was meantas premedication. Rituximab, Mycophenolate and intravenous immunoglobulin were used pre- and post-desensitization protocol as for it and forimmune tolerance induction therapy. Results: The patient received all 16 recombinant Factor IX aliquots per the extended-infusion protocol with-out adverse/allergic reactions, reaching the goal of 500 UI cumulative doses. 24 hours later, the immune tolerance induction therapy was initiatedthrough daily 6 hour infusions for a total of 9 days (9 infusions), no adverse/allergic reactions were documented. To this day, specifically 6 monthsafter the desensitization protocol, our patient is still receiving immune tolerance induction therapy with no adverse effects reported. Conclusions:Desensitization enables the possibility for immune tolerance induction to those patients who burden severe hemophilia B with allergy to coagula-tion factors, dramatically promoting their quality of life and surviving possibilities. This is the first protocol of its kind that has been carried out inMexico and Latin America, in addition to being successful, which will have the possibility to be reproduced and improved for the close needs ofthis special group of patients.

PE15-2 Perforating folliculitis triggered by bevacizumab administration

Ayano Maruyama, Risa Tamagawa-Mineoka, Koji Masuda, Norito Katoh (Department of Dermatology, Graduate School of Medical Science, KyotoPrefectural University of Medicine, Japan)

Perforating dermatosis presents with a characteristic skin change resulting from the transepidermal elimination of denatured collagen and elasticfibers. In perforating folliculitis (PF), perforating dermatosis occurs in hair follicles, commonly in patients with renal failure and diabetes. The pa-tient was a 59-year-old Japanese woman diagnosed with uterine cancer, which was surgically removed in 2017. She received paclitaxel and car-boplatin for 6 months as postoperative chemotherapy, which was terminated without any particular skin problems. However, her uterine cancerrecurred in 2018, and bevacizumab administration was started. Owing to intense itching on the back 1 month after treatment initiation, she vis-ited our department. At the first examination, papules that matched hair follicles were scattered on her back. We suspected perforating dermato-sis and performed a skin biopsy of the papules on her back. The pathological findings included a hair cross section in the horny layer. The portionconsidered as the hair follicle infundibulum was dilated and showed abscess and ulceration. Transepidermal elimination of collagen fibers from thedermis through the ulcer site was observed. Thus, we made a diagnosis of PF. Although a topical corticosteroid was applied during continuousbevacizumab administration, the rashes worsened. In 2019, bevacizumab administration was terminated. One month later, the rashes started toimprove and were eventually cured. To our knowledge, this is the first reported case of PF triggered by bevacizumab administration.

PE15-3 Successful oxaliplatin desensitization protocol

Ligia L Carrasco1), Sandra N González-Díaz2), Cindy E De Lira Quezada2), Rosalaura Villarreal-Gonzalez2) (Department of Allergy and Immunology,University Hospital “Dr José Eleuterio González”, Mexico1); Regional Center of Allergy and Clinical Immunology, University Hospital “Dr JoséEleuterio González”, Mexico2))

Introduction: Platinum compounds are frequently used for the treatment of colorectal cancer as initial chemotherapy. Oxaliplatin is a third-generation platinum used for the treatment of stage lll colorectal cancer and is associated with hypersensitivity reactions (HSR). The incidence ofHSR associated with oxaliplatin in patients with colorectal cancer is approximately 12%, with 1% to 2% of patients developing moderate to severereactions. Case Presentation: We present the case of a 54-year-old male patient with stage lll B colon cancer was diagnosed and chemotherapywith oxaliplatin was indicated by the oncology service. Within 20 minutes of the first cycle of 250 mg of oxaliplatin, the patient developed respira-tory symptoms that included dyspnea, laryngeal spam, foreign body sensation in the throat, nausea and diarrhea; therefore, the infusion of ox-aliplatin was suspended, and intramuscular epinephrine was administered and intravenous hydrocortisone and chlorphenamine with adequateresolution of symptoms. Intradermal skin test was performed at the concentration of 5mg/ml (dilution1:100), was positive. Due to the symptomspresented we decided to perform desensitization to oxaliplatin (total dose: 250mg) with a 3 bags 12 steps protocol with an initial concentrationdose of 1/100 of the total dose. The patient was premedicated 1 hour before with 10 mg clorpheniramine, 40 mg methylprednisolone, 8 mg ondan-setron and intravenous prophylactic fluids with normal saline solution. The procedure was carried out with close monitoring of vital signs in acourse of 5.56 hours with no hypersensitivity reactions. Discussion: Oxaliplatin, is a third generation platinum agent and first-line drug treatmentfor colorectal cancer. Approximately 50% of patients who are exposed to oxaliplatin may have hypersensitivity despite premedication. Desensiti-zation protocol induces tolerance to a drug temporarily and dependent on continuous exposure-ConclusionsThe safety of desensitization protocolsis well-known. This procedure has been evaluated in ambulatory settings where it is frequently used. In our patient the desensitization protocolwas successful, however a few patients with severe drug reactions cannot be managed despite adequately modified desensitization protocols andcomplete premedication.

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PosterSession

PE15-4 Two cases of severe drug hypersensitivity

Hideki Yoshikawa, Shoto Takemoto, Masaki Kusuda, Taisuke Eguchi (Department of Pediatrics, Kirishima Medical Center, Japan)

We treated two patients with severe drug hypersensitivity. Case 1: A 16-year-old Japanese male with partial seizures developed fever and gener-alized erythema 13 days after an administration of zonisamide. The zonisamide’s discontinuation (day 1) led to improvement by day 3, but he de-veloped fever again on day 11. The rapid test for group A streptococcus result was positive, and we started treatment with cefditoren pivoxil.The fever persisted, and he was admitted to our hospital on day 14. He presented conjunctival congestion, generalized erythema, cervical lympha-denopathy, leukocytosis, elevated C-reactive protein, and liver dysfunction. We suspected Kawasaki disease (KD), but echocardiography revealednormal coronary arteries. We diagnosed drug-induced hypersensitivity syndrome (DIHS) and started steroid therapy. An elevation of the titer ofantibodies against human herpes virus 6 in the blood (1:20 to 1:640) was observed during the disease course. We speculated that zonisamide wasthe causative drug, based on the positive results of a drug-induced lymphocyte stimulation test (DLST) on day 15. Case 2: A 13-year-old Japanesemale developed fever and generalized erythema a few hours after taking an over-the-counter drug containing acetaminophen for his cold symp-toms, including fever. The following day, he was administered baloxavir marboxil with a diagnosis of influenza A. His fever persisted, and he wasadmitted to our hospital on day 6 post-onset. He presented conjunctival congestion, generalized erythema studded with many small pustules, leu-kocytosis, and elevated C-reactive protein. We suspected KD, but echocardiography revealed normal coronary arteries. We began treatment withsulbactam/ampicillin based on the suspicion of bacterial infection, but the fever persisted. The following day, we diagnosed acute generalized ex-anthematous pustulosis (AGEP) and started steroid therapy. Desquamation appeared on day 10. We speculate that acetaminophen was the causa-tive drug, based on the positive DLST results on day 32. When drug hypersensitivity is suspected, it is essential to discontinue the suspecteddrug. Clinically, DIHS and AGEP may resemble bacterial infection and KD. Clinicians must recognize these two rare but different types of drughypersensitivity.

PE15-5 Tosufloxacin-induced acute generalized exanthematouspustulosis confirmed by a drug-induced lymphocytestimulation test

Takahiro Mizuta1), Aya Tanaka2) (Sakai City Medical Center, Japan1); Department of Dermatology, Sakai City Medical Center, Japan2))

A 47-year-old Japanese woman presented with acute-onset fever, intertriginous erythema, and small neck-localized pustules. A one-day treatmentwith oral tosufloxacin was administered for upper respiratory tract infection. The acute generalized exanthematous pustulosis (AGEP) validationscore was consistent with a definite diagnosis. The drug-induced lymphocyte stimulation test for tosufloxacin was positive despite a negativepatch test. Following drug withdrawal and oral/topical corticosteroid therapy, the patient recovered immediately. This first reported case oftosufloxacin-induced AGEP in the literature highlights tosufloxacin as a potential cause of severe cutaneous drug eruptions.

PE15-6 Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms triggered by lenalidomide

Shin-Ichi Osada1,2), Takahiko Sato1) (Department of Dermatology, Akita University Graduate School of Medicine, Japan1); Department of Dermatol-ogy, Nippon Medical School Tama Nagayama Hospital, Japan2))

Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare adverse drug reac-tion, in which drug allergy and viral reactivation are implicated in the pathogenesis of this disease. Here, we report the first Japanese case ofDiHS/DRESS triggered by lenalidomide, a derivative of thalidomide with more potent immunomodulatory and anti-tumor activities. A 59-year-oldman presented with a macuropapular pruritic rash on his face, trunk, upper and lower extremities associated with hyperemia (>38.5°C), swellingof the lower lip, and mild cervical lymphadenopathy. He was hospitalized for the treatment of multiple myeloma and received bortezomib, le-nalidomide, and dexamethasone (VRD) therapy. His cutaneous manifestations and high fever developed after two cycles of VRD therapy. Labora-tory examinations revealed leukocytosis with eosinophilia, the appearance of atypical lymphocytes, and increased levels of serum aspartateaminotransferase, alanine aminotransferase, lactate dehydrogenase, and γ-glutamyl transpeptidase. The titer of anti-human herpes virus-6 immu-noglobulin G (IgG) by fluorescent antibody assayincreased from <10 (at presentation) to ×640 (day 40). The titer of anti-cytomegalovirus IgG byenzyme immunoassay also increased from 9.3 to 17.9. A biopsy specimen from an infiltrated erythema on the abdomen showed perivascular lym-phocytic infiltration in the upper dermis and liquefaction degeneration at the dermoepidermal junction. These clinical and laboratory data fulfilledthe diagnostic criteria for DiHS/DRESS. Although his cutaneous manifestations and pruritus persisted after discontinuation of lenalidomide, ad-ministration of prednisolone (20 mg/day) gradually improved these symptoms. Importantly, pruritic cutaneous manifestations were recapitulatedby administering pomalidomide, another thalidomide derivative. Although it is known that DiHS/DRESS is caused by a limited number of drugs,mainly anticovulsants, our case suggests that thalidomide derivatives can potentially induce this disease.

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PosterSession

PE15-7 A new desensitization protocol in a case of acyclovir hypersensitivity in a child

Teresa Garriga-Baraut (Department of Pneumology, Allergy and Cystic Fibrosis Pediatric Allergy Unit, Spain)

Background: Hypersensitivy reactions to acyclovir can occur in children. Most of them are mediated by immunoglobulin E and clinical manifesta-tions can vary from mild (pruritus/urticaria/angioedema) to severe (anaphylactic reactions). In herpes infections, it could be the antivirus choice.Moreover, it is also used as a prophylactic treatment. Therefore in cases of IgE mediated allergy, acyclovir desensitization is a reasonable optionand can be performed successfully in most cases. However, in the literature, there are no publications about this procedure being done orally inpediatric patients. Methods: A 9-year-old girl, who had received acyclovir intravenously as a profilaxis treatment for herpes virus due to leuke-mia. She experienced generalyzed urticaria and pruritus 30 minutes after receiving acyclovir intravenously in two different occasions. In bothcases, symptoms were limited to approximately 60 minutes without the need of treatment. A skin-prick test with acyclovir was positive. Due tothe need of prophylactic treatment at home with acyclovir, an oral desensitization protocol was performed. Results: The prophylactic dose re-quired was 200 mg. (2,5 ml.) every eigth hours. For the procedure a solution of acyclovir of 400 mg./5ml. was used. An oral desensitization protocolof four doses that lasted three hours was developed. The first dose was 0.2 ml. and was progressively doubled every 30 minutes till full dose wasachieved. These doses administered were as follows: 0.2 ml. 0.4 ml. 0.8 ml. and finally 1.6 ml., reaching a total cumulative dose of 240 mg. (3.0 ml.).Conclusions:We report the first pediatric case of rapid oral desensitization to acyclovir in a child with urticaria due to IgE mediated allergy toacyclovir. Desensitization procedure should be considered in IgE mediated reactions to acyclovir when this treatment is required and there areno other options.

PE15-9 Respiratory complications of Stevens-Johnson syndrome (SJS): 3 cases of SJS-induced obstructive bronchiolitis

Yurie Seto1), Yoshiko Kaneko1), Chie Sotozono2), Mayumi Ueta2), Satoshi Sato3), Hiroshi Date4), Akihiko Yoshizawa5), Takayuki Shimamoto1),Masahiro Iwasaku1), Tadaaki Yamada1), Junji Uchino1), Nobuyuki Hizawa6), Koichi Takayama1) (Department of Pulmonary Medicine, Kyoto Prefec-tural University of Medicine, Japan1); Department of Ophthalmology, Kyoto Prefectural University of Medicine, Japan2); Division of Infectious Dis-eases and Immunology, Saitama Children’s Medical Center, Japan3); Department of Thoracic Surgery, Kyoto University, Japan4); Center for Ana-tomical, Pathological and Forensic Medical Reserarches, Kyoto University, Japan5); Department of Pulmonary Medicine, Tsukuba University, Ja-pan6))

Background: Stevens-Johnson syndrome (SJS) and its sever form, toxic epidermal necrolysis (TEN), are rare intractable diseases with docu-mented adverse drug reactions, eruption of mucocutaneous blisters, and epithelial sloughing. The 6-week and 1-year fatality rates of acute phaseSJS/TEN are 23% and 34%, respectively and are directly correlated to comorbidities. Death occurs primarily due to chronic respiratory failure;however, because of sporadic disease, the factors underlying respiratory complications remain unknown. Bronchiolitis obliterans (BO) is a severerespiratory complications of SJS/TEN and results in peripheral airway lumen occlusion with granulation or fibrous tissue. Method: We experi-enced 3 cases of BO associated with SJS. Result: They exhibited varying clinical courses. Chronic progression over >10 years, subacute worsen-ing at approximately 2 years, and acute bronchiectasis within a few months after disease onset. Rapidly progressing respiratory failure is a seri-ous complication among patients with cystic bronchiectasis. Conclusion:We report our experiences and clinical information on respiratory com-plications of SJS and consider them pathologically. In Relief System for Suffers from Adverse Drug Reactions in 2007, a total of 1,645 cases werefiled per year, and 52 out of them had SJS, and one of them had secondary BO. We also recommend considering lung transplantation when find-ings of bronchiectasis are observed.

PE15-10 Peripheral blood lymphocyte decrease at the onset of drug eruption

Daiki Nomura1), Shigeko Inokuma1), Satoshi Miike1), Manami Kato1), Jun Kanemura1), Takahide Akimoto2) (Department of Allergy and RheumaticDiseases, Chiba Central Medical Center, Japan1); Department of Dermatology, Chiba Central Medical Center, Japan2))

Objective: Diagnosis and pathogenesis of drug-induced eruption are not yet clarified. Cells of immune system would be involved, and histologi-cally lymphocytes are observed at the cite. Whether peripheral lymphocyte count changes is better examined. Patients and Methods: Patientswho were hospitalized in Chiba Central Medical Center from Jan. 2016 to Dec. 2019, for skin rash diagnosed as induced by a drug, by the doctor incharge, were examined for background, primary disease, suspected drug, counts of peripheral blood lymphocyte, eosinophil and neutrophil, andserum CRP level, at the baseline, at the onset and after recovery. Results: Ten patients were included (7 males and 3 females, 67.3±19.0 yrs). Theprimary diseases varied including angina in two and rheumatoid arthritis in one. Suspected drugs included contrast agent in two and salazosul-fapyridine in one. Peripheral blood lymphocyte count at three measuring points were 2510±940/mL (n=6), 1362±388/mL (n=10)(p<0.05 vs. base-line) and 2520±631/mL (n=10)(ns vs. baseline, p<0.001 vs. onset). Eosinophil counts were 143±120/mL (n=6), 203±314/mL (n=10)(ns vs. baseline)and 367±308/mL (n=10)(ns vs. baseline, ns vs. onset). Neutrophil counts were 4780±1516/mL (n=6), 8167±4820/mL (n=10)(ns vs. baseline) and5330±1802/mL (n=10) (ns vs. baseline, ns vs. onset). CRP levels were 1.50±1.61 mg/dL (n=6), 3.49±4.21 mg/dL (n=10)(ns vs. baseline) and 1.35±1.26 mg/dL (n=10)(ns vs. baseline, ns vs. onset). Discussion: Peripheral blood lymphocyte count clearly decreased at the onset to a half level of thatat baseline, and returned to the baseline level after the recovery. Lymphocyte count level would provide a useful indicator suggestive of drug in-duced skin rash. Eosinophil count did not show a meaningful change through a clinical course. Neutrophil count showed no significant change.CRP level showed a wide range from negative to high, possibly reflecting a status of the primary disease.

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PosterSession

PE15-11 Drug reaction with eosinophilia and systemic symptoms (DRESS)

Nurul Iman Nilam Sari, Endah Citraresmi (Department of Child Health, Harapan Kita Women and Children Hospital, Indonesia)

Background: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a distinct, severe, idiosyncratic reaction to a drug char-acterized by a prolonged latency period. This syndrome causes a diverse array of clinical manifestations, usually fever, rash, lymphadenopathy,eosinophilia, and a wide range of mild-to-severe systemic presentation, from 2 to 8 weeks after initiating the offending drug. DRESS syndrome is alife-threatening disease with a mortality rate of around 10%. Patients may suffer morbidities due to DRESS syndrome-related organ damage ordue to treatment-related complication. Method: Case presentation Results: A 2 year 6 months-old girl was admitted to our hospital due to skinrash on the body surface area. She had consume amoxicillin 1 week before admission. Cutaneous lesion showed frequently of polymorphic presen-tations as maculopapular, urticarial, exfoliative, lichenoid, pustular, and purpuric lesion. On physical examination, we found facial edema, lymphnode enlargement and organomegaly. Laboratory findings showed eosinophilia 17.7% (2,170/uL) and atypical lymphocytosis. Two weeks after thestart of the eliciting drug, Serum alanine aminotransferase (ALT) was 1,360 U/L and alkaline phosphatase (ALP) was 3,513 U/L. The value of R ra-tio, which is the ratio of serum ALT results to ALP with upper limits of normal range (ULN) were (ALT/ULN 41.2) and (ALP/ULN 109.7) whichmeans hepatocellular type liver injury. Glomerular Filtration Rate (GFR) was 13.8 mL/min/1.73 m2 with Ureum 291 mg/dl Creatinin 4.8 mg/dl fig-ured acute kidney injury because of drug-induced. Radiology findings showed interstitial pneumonia. There were no cardiac involvement andneurologic manifestations, but she had severe opportunistic infections. Immediate withdrawal of the inciting drugs has been done in this patient.The treatments were systemic corticosteroids started in 0.5-1 mg/kg/day, intravenous immunoglobulin (IVIG) and supportive care. Unfortu-nately in the sixth weeks of treatment patient died. Conclusion: DRESS syndrome is a complex disease that is comprised of complicated interac-tions among drugs, viruses and immune responses. Dress syndrome must be recognized promptly and the causative drug withdrawn. The earlierthe drug withdrawal, the better the prognosis.

PE15-12 Desensitization protocol to paclitaxel: the importance of proving the ideal treatment in a patient with anaphylaxis and breast can-cer

Cindy E De Lira Quezada, Sandra N González-Díaz, Rosalaura Villarreal-Gonzalez, Rodrigo A De la Cruz-Cruz (Regional Center of Allergy andClinical Immunology University Hospital “Dr José Eleuterio González”, Mexico; Autonomous University of Nuevo Leon, Mexico)

Introduction: Among the most common chemotherapy agents implicated in anaphylaxis are taxanes. Hypersensitivity reactions occur in 1% ofcases and are generally attributed to surfactants, however immediate IgE reactions have been reported. Case Description: A 45 year old femalepatient with stage IIA breast cancer diagnosed on December 2019, started chemotherapy with 135 mg of paclitaxel. However 5 minutes after thefirst dose she presented nausea, abdominal pain, generalized erythema, chest tightness and dyspnea; 200 mg of hydrocortisone was administeredby the Oncology Service with complete resolution of symptoms at the moment and was discharged. 5 hours later the patient presented onceagain chest tightness, difficult breathing and referred a feeling of incontinence. She arrived at our service and was administered 0.5 mg of intra-muscular epinephrine and 200 mg of hydrocortisone with resolution of symptoms after 10 minutes. She remained under surveillance for 8 hourswith no further reactions. On the next visit, we performed skin tests with paclitaxel (1mg/1mL): prick tests were negative, intradermal test (0.01mg/mL) 0.05 mL was positive (wheal was 5 mm greater than negative control). A desensitization protocol was performed with a 3-bag 12 steps, 6hour method at increasing concentrations of 0.005, 0.05 and 0.54 mg/mL with a total dose of 135 mg. Methylprednisolone (40 mg), clorpheniramine(10mg) and ondansetron (8 mg) were used for premedication. We administered saline solution at 100 mL/hour throughout the first 11 steps withan increase to 250 mL/hour after step 12. The procedure was well tolerated and continues up to date. Discussion: It is important to inform suc-cessful protocols in order to provide an alternative treatment opportunity for patients in need of this type of therapy. In this patient, alternativessuch as docetaxel was not available so paclitaxel represented the only alternative of its kind, being desensitization protocols the only therapeuticoption in order to accomplish control of the disease and improve her favorable outcome.

PE15-13 Rituximab desensitization in acute lymphoblastic leukemia pediatric patient with severe anaphylaxis

Rosalaura Villarreal-Gonzalez1), Sandra N González-Díaz2), Cindy E De Lira Quezada2), Ligia L Carrasco-Díaz2), Natalhie Acuña-Ortega2) (RegionalCenter of Allergy and Clinical Immunology, University Hospital, Faculty of Medicine, Autonomous University of Nuevo Autonomous Universityof Nuevo Leon, Mexico1); Allergy and Clinical Immunology, University Hospital, Mexico2))

Introduction: Rituximab is a monoclonal antibody (mAb) and is until now the most studied drug in CD-20 positive acute lymphoblastic B-cell leu-kemia. Hypersensitivity reactions (HSRs) to rituximab occur during the first infusion in 29% to 40% of patients. Commonly, these hypersensitivityreactions are the result of a release of cytokines, although IgE mediated reactions have also been reported. Case presentation: A 7-year-old fe-male patient with diagnosis of CD-20 positive acute lymphoblastic B-cell leukemia was indicated rituximab treatment by the pediatric hematologyservice; 30 minutes after the first administration of 300 mg of rituximab the patient started with generalized rash, nausea, vomiting, tachycardia,dyspnea, foreign body sensation, oxygen desaturation until 89% and hypotension; therefore, the infusion of rituximab was suspended, and intra-muscular epinephrine was administered as well as intravenous hydrocortisone and chlorphenamine and supplemental oxygen supply with ade-quate resolution of symptoms. Intradermal skin testing with rituximab at the concentration 1 mg/ml (dilution 1:10), was positive. Desensitizationto rituximab was indicated by our service with a 4 bags 16 steps protocol with an initial concentration dose of 1/1,000 of the total dose. The patientwas premedicated 1 hour prior with intravenous chlorphenamine methylprednisolone and ondansetron. Intravenous prophylactic fluids with nor-mal saline solution were administered during the infusion. The procedure was carried out with close monitoring of vital signs in a course of 6.67hours, without presenting hypersensitivity reactions. Discussion: HSR to rituximab may be induced by the activation of mast cells and basophils.Reactions occur most frequently during or shortly after the first infusion and may require desensitization. Conclusion: Desensitization protocolsare developed when there is no alternative drug for the underlying condition. In patients with CD-20 positive acute lymphoblastic B-cell leukemia,rituximab is essential for a favorable outcome.

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PosterSession

PE15-16 Biological treatments in allergy: a worldwide survey on prescription and management of hypersensitivity reactions

Leyla Barakat1), Luciana Kase Tanno1,2,3) (Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud-de-Villeneuve, Département de Pneu-mologie et Addictologie, University of Montpellier, France1); Sorbonne Université, INSERM UMR-S 1136, IPLESP, Equipe EPAR, 7513, France2);WHO Collaborating Centre on Scientific Classification Support, France3))

Background: Allergy is witnessing major advancements: the increasing recognition of the specialty worldwide and the advent of biologicalagents (BA) for treating allergic diseases. Given the novelty of these therapeutics, we aimed to explore by a worldwide survey, the prescriptionand the management of hypersensitivity reactions of BA in Allergy. Method: We built up an anonymous online questionnaire on Google Forms,that we sent by mail and social media via a link on the 4th of February of 2020 and received responses till the 10th of March of 2020. Results:Wereceived a total of 348 completed surveys from 59 countries, with a majority from Europe (62.6%). Eighty-seven per cent of responders were aller-gists, 48.5% were exclusively allergists. Allergy was mentioned as a full specialty in 69.5% of cases. Seventy one percent of responders confirmedthe right of prescription of BA for allergists in their country and 78.4% prescribed BA in their clinical practice. Europe included almost all the al-lergists who did not have the right of prescribing BA (95.5%), specifically France (91%). The most prescribed BA were Anti IgE (Omalizumab)(78.1%) followed by anti IL5 (Mepolizumab, Reslizumab) (43.9%). The most declared hypersensitivity reactions to BA were local reactions (74.1%)followed by anaphylaxis like symptoms (6.8%). Responders mostly relied on published recommendations (45.4%) for the management of these reac-tions. For mild hypersensitivity reactions to a BA, responders mostly pursued the BA and treated the reaction symptomatically (54%). For moder-ate to severe reactions, the most common action was the switch of the BA to another one (40.5%). Allergic investigation was more frequent in thisscenario (28.1%). Desensitization was considered in 18.9% of cases. These hypersensitivity reactions were reported in 48.8% of cases. Conclusion:BA are now a pillar in the treatment of allergic diseases, but their prescription is not authorized for allergists in all countries. BA showed to begenerally safe but severe hypersensitivity reactions could occur with a lack of consensus on the management.

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PosterSession

Poster Session 16Education and allied health

PE16-1 What is the expected role of a pediatric allergy-pulmonologist in a medium-sized general hospital? a descriptive analysis of the 5years’ consultation

Dong In Suh1), Jun-Hyuk Song2) (Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Hospital, Re-public of Korea1); Department of Pediatrics, Myongji Hospital, Republic of Korea2))

Purpose:We aimed to evaluate the common reasons and characteristics of the 5-year inpatient consultation to the department of pediatric allergyand pulmonology (PAnP) in a medium-sized general hospital.Methods:We retrospectively reviewed medical records of inpatient-consultations toPAnP from March 2015 to February 2020 in the Myongji Hospital, a medium-sized general hospital as a branch of HanYang University MedicalCenter. The data were descriptively analyzed for reasons and characteristics. Results: A total of 367 inpatient-consultations were reviewed. A to-tal of 37.5% (150 of 400) of inpatient consults were for evaluation and management of common cold, 26.2% (105 of 400) were lower respiratory tractinfection, and 15.2% (61 of 400) were upper respiratory tract infection other than the common cold. As for allergy-related topics, 4.8% (19 of 400)were asthma and 3.0% (12 of 400) were allergic rhinitis followed by a food allergy, urticarial and drug and atopic dermatitis (3, 2, 1 cases each).More than one reason was given for 9.0% (33 of 367) of consultation. We received 21.0% of consultation from the pediatric departments and, inter-estingly, 70.8% from physical medicine and rehabilitation. Conclusion: In a general hospital, doctors in PAnP were requested to only a few special-ized topics. Understanding common reasons and characteristics for inpatient-consultations would suggest what the PAnP fellowship programshave to focus on.

PE16-2 Prevalence and predictors of incorrect use of inhaler device in patients with obstructive lung diseases

Hiroyuki Tamiya1), Akihisa Mitani1), Toshihide Abe2), Kousuke Eitoku2), Maiko Yamada2), Kazuo Takayama2), Yoshiyuki Ohno2), Yukie Nagase2),Goh Tanaka1), Hiroshi Suzuki2), Takahide Nagase1) (The Department of Respiratory Medicine, The University of Tokyo Hospital, Japan1); The De-partment of Pharmacy, The University of Tokyo Hospital, Japan2))

Background: Proper use of inhaler devices is a key factor for the treatment of obstructive lung diseases including asthma and chronic obstruc-tive pulmonary disease (COPD). Methods: To evaluate the inhalation technique and to assess the prevalence and the factors associated with in-haler device handling error, we retrospectively collected the data of outpatients with obstructive lung diseases referring to our hospital who hadreceived inhalation technique assessment by pharmacists. Patients’ characteristics including age, gender, diagnosis, duration of disease, period ofinhaler device use, exacerbation frequency, pulmonary function and use of multiple inhaler devices were analyzed. Results: Of the 85 patients in-cluding 47 patients with asthma and 30 patients with COPD, 45 (53%) made at least one handling error. Handling errors were widely detectedamong users of all types of inhalers, ranging from 53% for dry powder inhalers (DPIs), 55% for pressurized metered dose inhalers (pMDIs) and68% for soft mist inhalers (SMIs). Critical errors, which could substantially affect dose delivery to the lungs, were observed in 12% of patients.These errors were detected independently of types of inhaler device (DPIs, 9%; pMDIs, 11%; SMIs, 12%). Higher age was associated with both mi-nor and critical inhalation technique error. Conclusion: Inhaler device handling error is commonly observed in patients with obstructive lung dis-eases. Clinicians should pay attention to patients’ inhalation technique in the management of these diseases.

PE16-4 Efficacy of adrenaline auto-injector diary

Taku Oishi1), Kouhei Hagino2), Hajime Kuroiwa3), Mikiya Fujieda1) (Department of Pediatrics, Kochi Medical School, Kochi University, Japan1); De-partment of Pediatrics, Kochi Prefectural Hata Kenmin Hospital, Japan2); Integrated Center for Advanced Medical Technologies, Kochi MedicalSchool, Japan3))

Background: Adrenaline auto-injector (AAI) is not used correctly by patients and their caregivers because of lack of training. The aim of thisstudy was planning for how to keep on their proper use for AAI. Methods:We recruited patients prescribed AAI or their caregivers. At enroll-ment, they were asked to demonstrate use of a trainer device and they were given a calendar as a diary. They were asked to mark on the daythey practice for a year. After one year, we evaluated their performance again. Their skills were evaluated in five steps that consisted of a) how tohold the AAI, b) removing the cap, c) selecting the mid-anterolateral thigh as the correct site of injection, d) hold firmly in place for 5 seconds, and,e) massage after injection. The primary endpoint was the percentage of participants that correctly used AAI one year after enrollment. Results:A total of 102 participants were registered. At enrollment, 82 participants who had previous AAI prescription history, 38 of 82 (46.3%) used cor-rectly. Except for evaluation items of d) and e), 55 of 82 (67.1%) used correctly. Ninety-seven participants could be confirmed after one year, and 81of them (83.5%) used AAI correctly. We excepted multiple prescription cases including cases in which siblings having AAI, cases who used in-creased dose (0.3 mg) during this study period, and cases who could not be evaluated in one year, and cases in which the number of practice andlatest practiced date were not confirmed on the calendar(n＝23). The pass rate at the end of the study was 87.0%, and 16 had practiced more than7 times. Conclusion: Distributing the diary was effective in maintaining the adrenaline auto-injector skill properly. We thought that the partici-pants had kept on their motivation of practice of AAI by the diary.

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PosterSession

PE16-5 Changes of prehospital management of anaphylaxis in pediatric patients between 2018 and 2013

Chikako Motomura, Takeshi Oki, Masatoshi Wakatsuki, Toshiaki Kawano, Koki Okabe, Takehito Fukushima, Daisuke Yasunari,Hiroshi Mastuzaki, Mihoko Iwata, Yoko Murakami, Naohiko Taba, Satoshi Honjo, Hiroshi Odajima (Department of Pediatrics, National HospitalOrganization, Fukuoka National Hospital, Japan)

Background: Despite several recommendations, adrenaline auto-injector is poorly prescribed as prehospital management for anaphylaxis. Theaim of this study is to investigate the recent changes in the prehospital management of anaphylaxis in pediatric patients.Methods:We retrospec-tively compared the clinical characteristics of pediatric food allergy patients, who were hospitalized to our institute for anaphylaxis during the pe-riod from October 2018 to March 2019, with those from October 2013 to March 2014. The medical records were checked for causing foods, trigger,location, prescription and/or usage of adrenaline auto-injector, wheezing at admission, and treatment in our institute. Results: Consecutive 29 pa-tients (20 males and 9 females, median age 4.9years) from October 2018 to March 2019 were compared with 31 patients (22 males and 9 females,median age 3.7years) from October 2013 to March 2014. There were no significant differences in age, gender, causing foods, or wheezing at admis-sion. Milk, wheat, and egg accounted for more than half of the causing foods in both patients group. In 2018-2019, compared to 2013-2014, the inci-dence at home or relative’s home decreased, while nurseries, schools, and restaurants increased (p<0.05). As for the trigger, accidental causingfood ingestion were significantly decreased (p<0.01). On the other hand, patients use of adrenaline auto-injector (p<0.001), and ambulance trans-portation (p<0.05) were increased. In 2018-2019, only 5 patients required intramuscular adrenaline treatment after admission, compared to 13 in2013-2014 (p=0.05). Conclusion: Our in and out-of-hospital education for the past 5 years have improved prehospital management of anaphylaxisfor children with food allergies.

PE16-6 An educational workshop to expose clinical research investigators and related personnel to research ethics

Hiroaki Yanagawa1), Kenshi Takechi1), Masayuki Chuma1), Yasutaka Sato1), Chikako Kane1), Satoshi Sakaguchi1), Kaori Doi2), Yusuke Inoue3),Kenji Matsui4) (Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, Japan1); Department of Research Eth-ics & Bioethics, National Cerebral and Cardiovascular Center Research Institute, Japan2); Department of Public Policy, Institute of Medical Sci-ence, the University of Tokyo, Japan3); Division of Bioethics and Healthcare Law, National Cancer Center Japan, Japan4))

Background: To conduct biomedical research, including allergology, the role of research ethics consultants is increasing to the point where theyhave an advisory capacity for clinical research investigators in each research institute. At present, we are establishing an educational system forsuch professionals, including teaching materials and training methods, and have held nationwide educational workshops. The original purpose ofthese workshops was to examine the usefulness of the developed system and to provide realistic training for consultant candidates, who make upthe majority of the workshop participants. In addition to these candidates, for this session, we encouraged clinical research investigators and re-lated personnel to participate in a pilot workshop and examined its usefulness as an opportunity to provide exposure to research ethics. Method:We held a pilot one-day workshop in October 2019 in Tokushima, Japan. After a basic lecture in research ethics, two sets of materials (Case 1 cov-ering an issue in a clinical trial and Case 2 covering an issue in human biological specimens) were used for group discussion. A 30-item self-reporting anonymous questionnaire was provided at the end of the workshop. Results: Among 13 participants, 9 (70%) were clinical research in-vestigators and related personnel and 6 (46%) had no direct intention to act as consultants. The tendency was observed that Case 2 was more diffi-cult than Case 1. On the other hand, both cases were generally accepted as educational materials and satisfaction was observed in both cases.Overall, the one-day format seemed to be regarded as insufficient for training time. Discussion: Clinical research investigators and related person-nel seem to be more familiar with the case of clinical trials than that of biological materials. Because the evaluations of the cases were generallypositive, we are going to further examine the usefulness of participation in the workshop in the cultivation of research ethics in the investigatorcommunity. Acknowledgment: This project was supported by the Japan Agency for Medical Research and Development under Grants Number[19oa0310003].

PE16-7 “Breathe power go!” ; an easy and fun game to identify obstructive pulmonary disorder

Yurie Namoto1), Tetsuya Oguma1,5,6), Makoto Yamazaki1,3), Mayu Aizawa1,4), Daiki Hira2,5), Masahumi Yamaguchi6), Emiko Ogawa6), Yuko Komase5),Yasutaka Nakano6) (Department of Respiratory Medicine, Oguma Family Clinic, Japan1); Faculty of Pharmaceutical Sciences, Ritsumeikan Univer-sity, Japan2); Faculty of Medicine, Shiga Medical University, Japan3); Faculty of Life Sciences, Ritsumeikan University, Japan4); Association of Inha-lation therapists, Japan5); Department of Respiratory Medicine, Shiga Medical University, Japan6))

Background: Asthma and COPD are obstructive pulmonary diseases which require spirometry for the diagnosis. However, the general public donot know obstructive pulmonary diseases well. In addition to that, spirometry requires considerable labor and cost. Purpose: To develop a funand easy game that can easily identify the people who may have obstructive pulmonary disorder. Method:We devised a game to estimate a pul-monary function using a straw and a bead. Briefly, a bead is embedded in a straw, and people blow into a straw to fly a bead. The flying distanceof a bead is recorded. The flying distance of the bead and the peak flow value of 13 healthy volunteers showed a considerable correlation (R2=0.756). The predicted flying distance of the beads was estimated based on the relationship between the flying distance of the beads and the peakflow value in consideration of age, sex, and height. We named this game“Breathe Power Go!”and performed in the health-related events. Results:We performed this game at 9 health-related events. A total of 2086 participants were divided into three groups; ◎ who blew over a predicted fly-ing distance, X less than half, and ○ between ◎ and X (421, 1531 and 132, respectively). We then examined 132 (6.34%) X people using a peak flowmeter, which revealed that 21 (0.98%) were classified as having low peak flow. Conclusion: We could investigate a wide range of people easily,while they enjoyed the game.

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PosterSession

PE16-8 The pack cooking that helps food allergic patients at the time of disaster, focused on weaning foods

Naoko Okishima, Saki Ogura, Kyoka Nishimaki, Haruna Nakayama, Kana Miyahara (Department of Health and Nutritional Science, MatsumotoUniversity, Japan)

Background:Many disasters have occurred in Japan. Once a huge disaster occurs, a lot of people are forced to live as refugees. They must stayat the temporary evacuation shelter and must take rations for a certain period. However, persons with food allergies cannot eat the rations be-cause they are supplied without considering the food allergy. According to the reports after the Great East Japan earthquake, the caregivers ofchildren with the food allergies were confronted with difficulties to get allergen-free foods. Thereafter nutritional support stations for the refugeeswho need dietary support were established when the disaster occurred. But it was not enough to support food allergic patients. Pack cooking at-tracted lots of attention after the Great East Japan earthquake, because the cooking method enable to cook by portable gas stove and to cook withless water. Since the ingredients were changeable in each bag, the pack cooking is convenient to make individual foods. From these, pack cookingis suitable for making allergen-free food. We have shown that the allergen cross contamination is hardly occurred among the bags during thecooking process. We have also proposed the cooking recipes for the weaning foods because it had been difficult to get them at the disaster.Meth-ods: The pack cooking recipes for the weaning foods without the seven-specified raw materials that cause the food allergy in Japan were de-signed originally or optimized from the recipe for children or adults. Ingredients were thinly sliced and put into the plastic bag made of the heat-resistance polyethylene with seasonings. The top of the bag was twisted and closed tightly. Then the bag was cooked in boiled water for up to 30min until the ingredients were fully cooked. Results and Discussions:We show ten recipes without seven food allergens. Because it is very diffi-cult to get foods for babies at the time of disaster, the pack cooking is valid and useful to prepare the weaning foods.

PE16-9 Interview with adolescent food allergy patients and their caregivers about self-management

Akiko Yamaide1), Yurika Yoshino2), Hironori Sato1), Yuzaburo Inoue1), Naoki Shimojo3), Akira Hoshioka1) (Department of Allergy and Rheumatology,Chiba Children’s Hospital, Japan1); Department of Nursing, Chiba Children’s Hospital, Japan2); Department of Pediatrics, Graduate School of Medi-cine, Chiba University, Japan3))

Background: Patients with food allergies and their families need to manage dietary avoidance and the risk of anaphylaxis in daily life. As food al-lergy patients grow up (transitioning from pediatric to adult care), the acquisition of patient self-management skills is a challenge for them andtheir caregivers. However, the actual self-management skills of adolescent patients have not been clarified. In this study, we conducted a surveyof adolescent food allergy patients and their caregivers in order to clarify the actual status of their self-management. Methods: Study subjectswere nine adolescent patients (median age 15 years old, range 9-19 years old) with food allergies (6 males, 3 females) and their mothers. All pa-tients had pediatric allergist-diagnosed severe food allergy with a history of anaphylaxis. All patients had epinephrine autoinjectors. A pediatricallergist or pediatric-allergy specialized nurse conducted the interview each participant individually. Results: The study found that there are indi-vidual differences in the learning of self-management among food allergy patients. Some patients did not fully understand the importance of theirresponsibility for the management of medicines or epinephrine autoinjector use for anaphylaxis, but some patients understood those very welland had excellent self-management skills. Most mothers expressed concern and anxiety about their children not fully understanding the admini-stration of their medications and how to respond when they are ill, and were unsure of how to get involved in promoting patient independenceand developing self-care skills. Conclusions: In food allergy patients, it is very difficult to learn self-management skills. Clinicians should first prop-erly understand the individual problems and difficulties of the development of self-management in adolescent patients and their families. Based onthose understandings, it is very important to provide the necessary support to patients and their families to improve their self-management skills.

PE16-10 The actual condition of bronchial asthma patients in Japanese students

Takanori Imai (Department of Pediatrics, Showa University School of Medicine, Japan)

Objective: The management of bronchial asthma patients in Japanese students has improved remarkably in the last few years, and asthmadeaths are no longer present. However, the actual conditions of recent students with moderate or mild type of bronchial asthma are not clear.Method: The survey was conducted by the Japan School Health Association in the fall of 2019 via a questionnaire. A survey was done at schoolsnationwide, which were randomly selected. The questionnaire was distributed at schools, responded to by parents, and collected at schools. Sur-vey items included the presence of bronchial asthma based on the diagnosis of a physician, difficulty in school life due to asthma, and symptomssuch as wheezing. Result: We obtained answer from a total of 18865 students from elementary school to high school, with a response rate of77.7%. Bronchial asthma was observed in 4.0%, gradually decreasing from 6.2% in first graders to 1.9% in high school students. Over the past year,25.5% have missed school due to asthma, and 14.6% have either been late for school or left early. Routine use of steroid inhalers was 42.8% and leu-kotriene receptor antagonists were similarly 48.8%. The proportion of children using leukotriene receptor antagonists tended to decrease withage. There was no age-related trend in steroid inhalation use. On the other hand, patches of bronchodilators were used daily by 29.1% and oralsteroids by 3.5%. 6.8% of students have wheezing in the past year, of which 5.1% had them 13 or more times in a year. 4.5% of students had sleepdisorder due to wheezing more than once a week. Conclusion: The management of children with bronchial asthma in Japan needs to look at thenext stage. That is, children with moderate or lower asthma should be treated for more stable management.

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PE16-11 Changes in self-care education for children with allergic diseases by medical staff in Japan: a report from a nationwide survey

Masami Narita1), Ikuyo Masuko2), Akira Akasawa Iino2) (Division of Allergy, Tokyo Metropolitan Children’s Medical Center, Japan1); NasunogaharaClinic, Japan2))

Background: Educating patients with allergies in self-care management is important for well control of the disease. Many physicians, however,cannot afford enough time for this purpose during regular medical visits under the current healthcare system in Japan. The aim of the presentsurvey was to investigate the current status of, and changes in, patient education for children with allergic diseases in Japan. Methods: A nation-wide survey of the members of the Japanese Society of Pediatric Clinical Allergy, including both physicians and nurses, was conducted by mail in2013 and online in 2018. The questionnaire addressed the characteristics of the medical institutions to which the members belonged, the currentstatus and the methods of patient education for children with allergic diseases. The responses to the two surveys, which were conducted fiveyears apart, were compared. Results: Two hundred fifty-seven members from 136 institutions, and 269 members from 79 institutions respondedto the questionnaire in 2013 and in 2018, respectively. The proportion of medical institutions in which nurses educated asthmatic children using aspacer for inhaled corticosteroid increased significantly (27.6% vs 51.9%) within five years. The portion of those in which nurses performed skincare education for patients with atopic dermatitis and that of those in which nurses educated patients in the use of adrenaline autoinjectors alsoincreased significantly from 35.6% to 63.3% and from 17.0% to 45.5%, respectively. Moreover, the methods of patient education have changed to in-clude demonstration by patients, such as application of ointment or performance with EpiPENⓇ trainer. However, the proportion of physicians in-volved in patient education did not change during the five-year study period. Conclusion: The nationwide survey suggested that medical institu-tions where nurses provided education to children with allergic diseases increased in the five-year study period in Japan, whereas physicians pro-viding patient education did not change significantly.

PE16-13 Attitude survey of medical professionals for pregnancy with asthma

Yuko Komase1), Naoko Uehara2), Takahiro Tsuburai1), Baku Ohyama1) (Department of Respiratory Internal Medicine, St Marianna University,School of Medicine, Yokohama-City Seibu Hospital, Japan1); Department of Allergology, Yokohama City Minato Red Cross Hospital, Japan2))

Purpose: A questionnaire was administered to medical professionals who attended a training course on inhalation guidance held in Kanagawaprefecture in the treatment of people who are pregnant and have asthma.Method: A questionnaire survey was conducted using the Internet forparticipants of the inhalation training class held in Yokohama in February 2020. The questionnaire covered whether the patient had been treatedfor asthma complications during pregnancy, how to treat using drugs, and what information is being used. Result: 1) There were 32 respondents:56.3% were pharmacists, 25.2% were practitioners, 12.5% were working physicians, and 6.3% were nurses. 2) Altogether, 56.3% of medical profes-sionals never had contact with a pregnant patient who has asthma. Overall, 31.3% of the reference information came from“Pregnancy and nurs-ing,”18.8% from the homepage of‘OKUSURI 110’, 12.5% from the package insert, and 12.5% from other doctors and pharmacists. 3) Regardinginhaled steroids, 34.4% prioritized budesonide, 34.4% no problems with any ICs, and 3.1% discontinued use because they were worried. 25%thought SABA could be used at all times. 4) Recognition of pregnancy and drug information centers was at 65.6%. Conclusion:Medical profession-als in Kanagawa are considered to have relatively abundant knowledge on how to use drugs and their degree of recognition. However, furtherawareness is needed for practitioners working with pregnant patients who have asthma.

PE16-14 Accelerometer-equipped external attachments to assist effective inhalation techniques

Miyuki Nishie1), Katsunori Masaki1), Hideo Nakada2), Taiko Ezaki1), Keeya Sunata1), Yuto Akiyama1), Risa Watanabe1), Misato Kuwae1),Shinichi Okuzumi1), Takae Tanosaki1), Hiroki Kabata1), Nobuyuki Togashi4), Tomoyuki Shimono4,5), Tohru Aomori2,3), Koichi Fukunaga1) (Division ofPulmonary Medicine, Department of Medicine, Keio University School of Medicine, Japan1); Division of Hospital Pharmacy Science, Keio Univer-sity Faculty of Pharmacy, Japan2); Department of Hospital Pharmacy, Keio University Hospital, Japan3); Kanagawa Institute of Industrial Scienceand Technology, Japan4); Faculty of Engineering, Yokohama National University, Japan5))

Background:More than half of the patients who are prescribed inhaled medications do not effectively use inhalation devices due to mishandlingor inadequate inspiration duration. Objective: To automatically track inhalation errors and incorrect motion, we investigated the motion of de-vices for inhaled medications using accelerometers. Methods:We made attachments for several devices (e.g., pressurized metered-dose inhalers[pMDIs], EliptaⓇ, and TurbohalerⓇ) for the fitting of three-axis accelerometers (inertial measurement units) using a 3D printer, and acquired theacceleration and angular velocity data of the device motion via microcomputers. We compared the motion data to the correct procedure patternsand examined the inconsistencies. Results:We detected errors in the shaking of pMDIs during drug priming based on incorrect motion data pat-terns, such as high amplitudes of acceleration and angular velocity. Similarly, handling rotation errors of the TurbohalerⓇ were determined by fo-cusing on the direction and frequency of z-axis angular velocity waveforms. In addition, we measured the inspiration time as the duration of thegentle acceleration curve on only one axis after the priming operation. This technique was useful for detecting critical inhalation errors becausepatients often misunderstood the correct inspiration duration (4 - 5 s for pMDIs and 2 - 3 s for dry powder inhalers). Conclusion: Accelerometer-equipped external attachments can detect errors in drug priming motions and inadequate inspiration duration, suggesting their potential useful-ness in clinical settings by providing appropriate support to patients who need inhaled medications.

183

PosterSession

PE16-15 Evaluation of educational program at NPO, EPAREC (Expert Patient in Respiratory Care) employing ABMA-C (Asthma Beliefand Medication Adherence) questionnaire that reflect adherence

Michiko Haida1,4), Bruce Bender2), Katsutoshi Ogawa3,4), Tamotsu Kiyohara4), Kenzou Nakao4), Takahiro Inoue1,4), Akihiko Hashiguchi5) (HanzoumonHospital, Japan1); National Jewish Health, USA2); Amica Life-science, Japan3); EPAREC (Expert Patient in Respiratory Care), Japan4); BiomedicalLaboratory, Japan5))

Education improve adherence to medication by recognition of risk as well as effect of appropriate therapy carried out under partnership withmedical staff. On the other hand, educator must recognize the need to, listen, educate, acknowledge, recommend and negotiate to sustain full part-nership with the patients. Barriers also exist on the side of the patients such as belief, attitude, life-style, social and economic status. Evaluation ofbarriers for better education is necessary for successful self-management of asthma. We will introduce a result of survey formulated to evaluateeffective education done at NPO, EPAREC, by employing simple questionnaire that reflect adherence.Method: ABMA (Asthma Belief and Medi-cation Adherence), a questionnaire developed to screen non-adherence. ABMA-A (10 items) inquire self management skills, such as, use of peakflow, asthma diary, use of controller and reliever, understanding action plan and avoidance measures, while ABMA-B (20 items) inquire beliefs, be-havior such as under estimation, anxiety, fear, sense of success and improvement, socio-economic status. Maximum likelihood estimate was donefor both ABMA-A and ABMA-B and 8 item chosen were employed as ABMA-C, a questionnaire that reflected social aspect, sense of success,anxiety, under-estimation, many of which reflect attitude concerning adherence. Cut off was 26 for ABMA-A, 25 for ABMA-C. ABMA-C was em-ployed to evaluate adherence of sub-group mainly at Hanzoumon Hospital, N=251(116 attended the EPAREC class, while 89 did not), and those atpharmacy A, (N=259), pharmacy B(N=11) and one for general public without chance of education(N=26). Result: Attendants of EPAREC markedhighest for ABMA-A, which correlated well with ABMA-C, reflecting good adherence with score at 27.7, followed by pharmacy B with score 27.6.Those not attending the asthma class marked 26.1, while those at pharmacy A had score of 24.1. Result from general public was 20.3. Conclusion:Highest marks for ABMA-C was observed for those who attended the EPAREC class, and may reflect high quality of education given by thisgroup which in turn may have had a role in enhancing adherence score reflected by ABMA-C.

PE16-16 Inhalation instruction with wearing masks under the Novel Coronavirus Disease 2019 (COVID-19) spread

Makoto Yamasaki1,2), Tetsuya Oguma1,2), Yurie Namoto1,3), Mayu Aizawa1,4), Shizuka Hattori5), Masahumi Yamaguchi2), Emiko Ogawa2),Yasutaka Nakano2) (Oguma Family Clinic, Japan1); Division of Respiratory Medicine, Department of Medicine, Shiga University of Medical Science,Japan2); Faculty of Pharmaceutical Science, Ritsumeikan University, Japan3); Faculty of Life Science, Ritsumeikan University, Japan4); Usagi Phar-macy Minami-Kusatsu Division, Japan5))

Background: Because of the spread of Novel Coronavirus Disease 2019 (COVID-19), conventional face to face inhalation instruction was found tobe an increased risk of infection. For that reason, both the instructor and the patient must wear masks during the instruction. Purpose: To inves-tigate the effect of inhalation instruction with masks compared to the conventional method. Method: This investigation included asthma patientswho received inhalation instruction for the first time between February 1, 2020 and May 25, 2020. The patients were divided into two groups; non-mask group and mask group. We made a questionnaire consisting of five questions to evaluate the understanding of inhalation instruction. Be-tween both groups, patient characteristics, questionnaire results, and Asthma Control Test (ACT) score were analyzed using statistical methods.Results: Sixteen non-mask patients and 21 mask patients were included. There were no statistically differences in age, gender, and ACT score be-tween the groups. The questionnaire revealed that there were no statistical differences in inhalation technique between the groups (P>0.05). Con-clusion: Even though the patients wear masks, we were able to perform the inhalation instruction sufficiently.

PE16-17 Attempt of online inhalation workshop during COVID19 epidemic: comparison withface-to-face workshop

Tetsuya Ueda1,2), Akira Shiraki2), Chie Yoshimura2), Yuko Komase2), Tetsuya Oguma2), Takeo Horie2), Naoko Uehara2), Yasuyuki Momose2) (Depart-ment of Respiratory Medicine, Osaka Saiseikai Nakatsu Hospital, Japan1); Non Profit Organization Association of Inhalation Therapists, Japan2))

Background: For medical staffs and doctors, in order to acquire the technique of inhalation instruction, it is necessary to practice at the work-shops. We held workshops using face-to-face role play and acquired skills. However, the trend of COVID-19 made it difficult for a large number ofmedial staff to hold seminars. Online role-play has started as a new method. Method: A questionnaire survey was conducted on 23 people whoparticipated in the online class. Results: 1) The overall impression is a) to see without any problems 86.4%, b) to hear without any problems 81.8%,c) difficulties in hearing the voice 9.1%, d) difficulties in viewing 4.5%, e) difficulties in the internet connection status 9.1%. 2) About the role play onthe internet is a) almost the same as the face-to-face role play 9.1%, b) more difficult than the face-to-face works 50%, c) much more difficult thanthe face-to-face works 22.7%. 3) The reasons are a) hard to understand mistakes 61.9%, b) hard to see inhalation devices on the angle 42.9%, c) smallsize of the screen 28.6%. 4) The merits of the online class are a) easy participation, b) infection prevention, c) easy to see the other person’s facialexpression, d) not to worry about time and surroundings. Conclusion: Online seminars have more difficulties than face-to-face workshops, butthey also have great advantages. It is important to get used to it, and this is a method that is expected to develop in the future.

184

PosterSession

Poster Session 17Food allergy-allergen and mechanisms

PE17-2 Clinical cross-reactivity to quail’s egg in patients with hen’s egg allergy

Masatoshi Mitomori1), Mari Takei2), Kinji Tada2), Makoto Nishino1), Noriyuki Yanagida1), Sakura Sato2), Motohiro Ebisawa2) (Department of Pediat-rics, National Hospital Organization Sagamihara National Hospital, Japan1); Clinical Research Center for Allergy and Rheumatology, National Hos-pital Organization Sagamihara National Hospital, Japan2))

Background: Generally, patients with hen’s egg (HE) allergy avoid eating quail’s egg (QE). However, there have been few reports on the clinicalcross-reactivity of HE and QE. The amount of protein is 6,300 mg for one HE and 1,100mg for one QE; in terms of protein amount, one QE isequivalent to approximately 1/6 of one HE. This study aims to evaluate the clinical cross-reactivity of HE and QE by performing oral food chal-lenges (OFCs).Method:We performed QE OFCs to HE allergic patients from March 2018 to October 2019. HE allergy was diagnosed with OFCs,which were performed stepwise starting from a low-dose (equivalent to 1/25 of a heated HE). Patients with negative results proceeded tomedium-dose (equivalent to 1/8 of a heated HE). Patients with a positive low-dose (threshold dose, less than 1/25 of a heated HE) or medium-dose(threshold dose, 1/251/8 of a heated HE) OFC were included in this study. QE OFC was performed with one heated QE. Results:We analyzed 18patients, of which 13 (72%) were male. The median age was 2.9 (range, 1.016.4) years. Eight (44%) patients had a history of anaphylaxis to HE. Themedian levels of HE white, HE ovomucoid, and QE white -sIgE were 9.95 (2.67365), 7.97 (<0.10191), and 4.15 (0.73>100) kUA/L, respectively. Thethreshold dose of HE was less than 1/25 of a heated HE in 4 patients and 1/251/8 of a heated HE in 14 patients. While all patients with a thresholddose less than 1/25 of a heated HE failed QE OFC, only 36% of patients with a threshold dose of 1/251/8 of a heated HE failed QE OFC. Conclu-sion: Clinical cross-reactivity to QE was observed in patients allergic to HE. Because the amount of protein and the threshold dose of HE and QEwere not simply proportional, the antigenicity of QE did not seem to be the same as that of HE.

PE17-3 Cross-allergenicity between hen’s egg and quail’s egg in patients allergic to hen’s egg

Mari Takei1), Masatoshi Mitomori2), Kinji Tada1), Noriyuki Yanagida2), Sakura Sato1), Akemi Saito1), Motohiro Ebisawa1) (Department of Allergy,Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan1); Department of Pe-diatrics, National Hospital Organization Sagamihara National Hospital, Japan2))

Background: Although the patients allergic to hen’s egg (HE) also need to eliminate quail’s egg (QE) from their diet, there are very few reportsabout the cross-allergenicity between these two eggs (HE and QE). In this study, we aimed to better understand the cross-allergenicity betweenthese eggs in children with immediate-type allergy to HE using an in vitro assay. Methods: Briefly, the hen’s egg white (HEw) and quail’s eggwhite (QEw) were extracted from the raw HE and QE, respectively. The children allergic to HE, who either failed or passed the QE oral food chal-lenge and were designated as QE-OFC positive group (n=9) and QE-OFC negative group (n=9), respectively. Sera from these 2 groups were usedin this study. Specific IgE levels to the HEw and QEw were measured using the fluorescent enzyme-linked immunosorbent assay (ELISA). ELISAinhibition and Western blotting assay using the pooled sera samples were conducted to assess the cross-allergenicity between HE and QE. Re-sults: A strong correlation in the IgE levels between HEw and QEw (r=0.948, p <0.001) was observed. In ELISA inhibition assay, QEw was notable to inhibit the HEw solid-phase to a significant extent. However, HEw was able to inhibit the QEw solid-phase even at a lower concentrationas compared to QEw. Similar inhibition patterns were observed in both, the QE-OFC positive and negative groups. In Western blot assay, the QE-OFC positive group reacted more strongly to ovalbumin and ovomucoid of QE than the QE-OFC negative group. Furthermore, by western blotanalysis assessing the inhibition using the QE-OFC positive group sera, HEw inhibited each QEw allergen, especially QE ovomucoid. Conclusion:In conclusion, there exists cross-allergenicity between HEw and QEw, and HE seems to be primary sensitizer in children with HE allergy. Differ-ences in the reactivity to QEw were observed between both, the QE-OFC positive and negative groups. Moreover, the clinical reactivity to QEmight be attributed to its reactivity to QE ovomucoid in particular.

PE17-4 Identification and characterization of perilla seed allergy in Korean children: clinical and immunological profiles

Kyunguk Jeong1), So-Yeon Lee2), Se-Ah Jeon1), Purevsan Gantulga1), Jin Young Nam1), Soo-Jong Hong2), Sooyoung Lee1) (Department of Pediatrics,Ajou University School of Medicine, Republic of Korea1); Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Cen-ter, University of Ulsan College of Medicine, Republic of Korea2))

Background: Perilla seeds (PS) are commonly consumed in Korea and have been recognized to cause immediate allergic reactions. However, re-ports on PS allergy are extremely limited worldwide. This study aimed to characterize clinical and immunologic profiles and develop diagnostictests of PS allergy in Korean children.Method: Twenty-two children with immediate symptoms to PS were recruited from the Department of Pe-diatrics in Ajou University Hospital and Asan Medical Center, from September 2016 to June 2019. Retrospective medical records and sera werecollected. Sera from 6 children tolerant to PS were used as negative control for skin prick test (SPT) and immunologic studies. Using our ownmade PS extract, we developed SPT and IgE enzyme-linked immunosorbent assay (ELISA) for diagnosis of PS allergy. IgE-Western blot, tandemmass spectrometry (LC-MS/MS), and IgE inhibition ELISA were performed. Results: The median age was 3 years (range: 1-12 years) and 63.6%were male. Anaphylaxis was noticed in 31.8%. SPT was performed in 14 children, and the grades according to the A/H ratio method were 2+ orabove in all cases. In ELISA system we developed, specific IgE (sIgE) was positive (higher than negative cutoff of arbitrary IgE concentration) in19 out of 22. SPT grades were 2+ in all 3 patients with negative sIgE in ELISA. More than 12 protein bands were identified by SDS-PAGE of PSextract, and about 8 IgE binding bands were apparently identified by IgE-Western blot. Among them, broad bands of 6-12 kDa and 30-36 kDawere identified as major allergenic components, recognized by 68.1% and 100% of the patients, respectively. At least 4 peptides including oleosinof perilla frutescens were suggested to be major allergens by LC-MS/MS, and further investigation is underway. In IgE inhibition ELISA, PSELISA was partially inhibited by sesame seeds (SS). Conclusion:We successfully developed SPT and measurement of sIgE using own made ex-tract. We identified major allergenic components of PS and partial cross reactivity with SS while further molecular analysis is needed.

185

PosterSession

PE17-5 Evaluation of multiple specific IgEs screening system DropScreenⓇ using a microarrayed allergen biochip

Yoshihiro Ito1), Sei Obuse1), Sakura Sato2), Motohiro Ebisawa2) (Emergent Bioengineering Materials Research Team, RIKEN Center for EmergentMatter Science, Japan1); National Hospital Organization Sagamihara National Hospital, Japan2))

Background: For convenient detection of specific IgEs at clinics, a new system was developed and commercially available from NipponChemiphar as DropScreenⓇ in Japan. Here it was compared with the conventional system. Methods: According to the protocol of DropScreenⓇ,20 microL of human sera were applied for the detection of specific IgE to 41 kinds of allergens including components of house dust, animal skinwaste, insects, pollens, fungi, and foods such as egg, milk, wheat, beans, vegetables, fruits, meals, fishes, and crustaceans. As the conventionalmethod ImmunoCAPⓇ was employed and the obtained values were compared. Results: DropScreenⓇ required 30 min for the automatic measure-ment, using the human serum. When the correlation with ImmunoCAPⓇ was investigated, high relative coefficient was obtained on buckwheat,milk, Dermatophagoides pteronyssinus, candita, mugwort, duck, and dog skin waste, and high overall agreement rate was obtained on soy bean,peanut, Dermatophagoides pteronyssinus, and Japanese cedar. Conclusion: The measured values obtained by DropScreenⓇ and ImmunoCAPⓇ

were highly correlated.

PE17-6 Comparison of IgE sensitization profile in shrimp allergic subjects between Hong Kong and Thailand

CYY Wai1), Agnes Sze Yin Leung1), P Vichyanon2), P Pacharn3), Nicki YH Leung1), K Xu1), Maco Cheuk Yin Lam1), Ting Fan Leung1) (Department ofPaediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong1); Samitivej Allergy Institute (SAI), Samitivej ThonburiHospital, Thailand2); Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Thailand3))

Background: Shrimp is a frequent cause of food allergy is Asia, but little is known regarding the IgE sensitization pattern to different shrimp al-lergens and cross-regional differences. This study aimed to compare the IgE sensitization patterns to shrimp allergens in allergic subjects be-tween Hong Kong and Thailand.Method: Subjects with a history of IgE-mediated shrimp allergy were recruited at the Prince of Wales Hospitalin Hong Kong (HK) and Siriraj Hospital in Thailand (Th). Double-blind placebo-controlled oral food challenge (DBPCFC) was conducted in subjectsrecruited in HK. Skin prick test (SPT) with shellfish extract was conducted in all recruited subjects. Serum specific IgE (sIgE) level to shrimp ex-tract (SE) was measured on ImmunoCAP and that to seven recombinant shrimp allergens were measured by ELISA. Results: A total of 16shrimp allergic subjects were recruited in Thailand, and 36 subjects with history of shrimp allergy were recruited in Hong Kong whom were clas-sified into the allergic (n=16) and tolerant (n=20) groups based on DBPCFC results. The allergic groups and tolerant group differed significantlywith respect to the wheal size in SPT, but not for sIgE levels to SE, by which 65% of the tolerant subjects also showed positive sIgE at 0.35 kUA/L cutoff. Multiple sensitization to shrimp allergens was common in subjects from both HK and Th. Tropomyosin (TM) represents the leadingshrimp allergen in Thai subjects with sensitization rate of 68.8%, followed by Troponin C (TnC; 50%) and fatty acid-binding protein (FABP; 37.5%).These components were also the top allergens in HK subjects but at a prevalence of 50% for TM and TnC, and 25% for FABP. Negative IgE re-sponses to all tested shrimp allergens was noted in 9/32 HK and Thai allergic subjects. Conclusion: The major shrimp allergens are different de-pending on the geographical regions and identification of novel shrimp allergens is needed to further understand the IgE sensitization profile.[This work is supported by the Hong Kong Institute of Allergy Research Grant 2017 and HMRF, HKSAR Government (06170856).]

PE17-7 IgE sensitization profile of fish allergic children in Hong Kong

Nicki YH Leung, Agnes SY Leung, Christine YY Wai, Jiaying Xu, Maco Cheuk Yin Lam, Gary Wong, Ting Fan Leung (Department of Paediatrics,The Chinese University of Hong Kong, Hong Kong)

Background: Diagnosis of fish allergy is often made by specific IgE measurement to representative taxonomic groups such as cod or salmon. TheIgE reactivity against species from different taxonomic groups are rarely reported. Method: IgE reactivity to 9 fish species (cod, salmon, tuna,halibut, grouper, herring, catfish, tilapia and grass carp) and 2 recombinant parvalbumins (rGad c 1 and rCyp c 1) were measured by ImmunoCAPassays in 166 fish allergic children in Hong Kong. Results: Ninety-eight (59.0%) subjects were IgE positive (0.35 kUA/L) to all 11 tests. Tilapia(mean IgE: 5.69 kUA/L) and grass carp (mean IgE: 5.09 kUA/L) were the most IgE reactive species while tuna (mean IgE: 0.75 kUA/L) and hali-but (mean IgE: 1.15 kUA/L) were the least IgE reactive species. Nevertheless, 5 subjects were only sensitized to tuna and salmon but not to anyother species. Interestingly, these 5 subjects were IgE negative against the two parvalbumins rGad c 1 and rCyp c 1 while most other subjects (n=157, 94.5%) were sensitized to rCyp c 1 and/or rGad c 1. IgE reactivity among the three freshwater fishes (tilapia, grass carp and catfish) werehighly consistent, with 134 subjects belonged to the same IgE class and only 2 subjects were discrepant. IgE reactivity among marine fishes werealso moderately consistent, with over 60% of the subjects belonged to the same IgE class and contradictory results were observed in 10% of thesubjects. Alternatively, the IgE reactivity between freshwater and marine fishes were rather inconsistent. Only about 35% of the subjects be-longed to the same class for both freshwater and marine fishes while about 25% of the subjects were discrepant. Conclusion: There were signifi-cant differences in IgE reactivity against different fish species, particularly between freshwater and marine fishes. Freshwater fishes were moreallergenic than marine fishes in our Chinese cohort, although monosensitization against tuna and salmon were observed. [This work is supportedby Innovative and Technology Fund (ITS/082/17) of Hong Kong SAR Government]

186

PosterSession

PE17-8 Cytokine profiles during oral food challenges for diagnosis of food protein-induced enterocolitis syndrome to egg yolk

Nobuko Akamatsu, Takashi Yamazaki, Yasuyo Kashiwagi, Takeaki Sasamoto, Masako Chiyotanda, Taro Miura, Ryuhei Nagao,Hisashi Kawashima (Department of Pediatrics and Adolescent Medicine, Tokyo Medical University Hospital, Japan)

Background: Food protein-induced enterocolitis syndrome (FPIES) is considered to be a gastrointestinal food allergy. In recent years, reports ofFPIES for solid food including egg have been increasing. Although there are several reports of clinical features with solid FPIES, few reportsshowed examining data associated to the pathogenesis. Method: Oral food challenge (OFC) for egg yolk (EY) was performed in two cases sus-pected of having EY FPIES (one was typical FPIES that is non-IgE-mediated, and another was atypical type that is IgE-mediated). Blood sampleswere collected before, 1 and 2 hours after the OFC, and at the time when symptoms appeared. Then the blood samples were examined, and cy-tokine profiles were analyzed. Case 1: 9-month-old girl. She experienced 2 episodes of frequent vomiting and clouded consciousness several hoursafter ingestion of EY. During OFC, the patient had large-volume vomiting and grossly bloody stool about 2 hours after ingestion. Bloody stools ap-peared only at the time of OFC. Case 2: 10-month-old girl. She had experienced multiple episodes of repeated vomiting after ingestion of EY. Dur-ing OFC, the patient had frequent vomiting about 3 hours after ingestion. Result: Blood tests in case 1 showed no elevation in the levels of specificIgE (sIgE) for EY, egg white (EW) and ovomucoid. That in case 2 showed elevated sIgE levels for EY and EW. Both skin prick test (SPT) andAllergen-specific Lymphocyte Stimulation Test (ALST) for EY and EW were negative. In both cases, cytokine profiles showed marked elevationof IL-2 and IL-8 at the time when symptoms appeared, but the levels of Th2 cytokines such as IL-4 and IL-5 showed no change. Conclusion: Therewas no difference in cytokine induction between atypical and typical EY FPIES. Therefore, it was suggested that neutrophil inflammation or cel-lular immunity may be involved in the pathogenesis of EY FPIES in both types.

PE17-9 Tropomyosin is a major antigen in childhood-onset shrimp allergy but a minor antigen in adults

Masashi Nakamura1,6), Akiko Yagami2,7), Yuri Takaoka3), Nayu Sato1,6), Satoshi Ohno4), Kayoko Suzuki2,7), Naoshi Shimojo1,6), Kyoko Futamura2,7),Yasuto Kondo5,7), Yuji Aoki1,6), Makoto Kameda3), Kayoko Matsunaga1,2) (Department of Integrative Medical Science for Allergic Disease, FujitaHealth University School of Medicine, Japan1); Department of Allergology, Fujita Health University School of Medicine, Japan2); Department of Pe-diatrics, Osaka Habikino Medical Center, Japan3); Faculty of Engineering, Gifu University, Japan4); Department of Pediatrics, Fujita Health Univer-sity School of Medicine, Japan5); General Research and Development Institute, Hoyu Co., Ltd., Japan6); Fujita Health University General AllergyCenter, Japan7))

Background: In Japan, there is a high incidence of shrimp allergy in individuals aged >7 years, with different clinical types in childhood-onset andadult-onset shrimp allergy. This study clarified the difference in causative antigens depending on the age of allergy onset.Methods: This study in-cluded 21 patients (mean age: 25 years; 10 males, 11 females) with immediate allergic symptoms after ingestion of and/or contact with shrimp, andwith positive skin-prick test; they were registered in a clinical registry for allergic diseases (MINERVA). Participants were stratified by the age ofonset, confirmed by medical consultation, into Group A (age <16 years; n=8) and Group B (age 16 years; n=13). Specific IgE (sIgE) for shrimp andmite were measured by CAP-FEIA method. Tropomyosin sIgE measurements and inhibition assays for shrimp and mite were performed byenzyme-linked immunosorbent assay (ELISA). Antigen analysis was undertaken by 2D Western blotting (2D-WB) using sera. Results: The preva-lence of atopic dermatitis (AD) was 54% and 25% in groups A and B, respectively. For groups A and B, shrimp sIgE-positivity rates were 85% and38%, respectively; 91% of the positive cases tested positive for mite sIgE. In the inhibition assay, shrimp and mite competed more frequently inGroup A than in B. In 2D-WB, tropomyosin and myosin heavy chain were the common antigens in groups A and B, respectively. Shrimptropomyosin-sIgE positive rates were 69% and 0% in groups A and B, respectively, and all positive cases tested positive for mite tropomyosin-sIgE. Conclusion: The major antigens of shrimp allergy are tropomyosin and the myosin heavy chain in childhood and adulthood, respectively,and vary by the age of onset. Thus, childhood shrimp allergy may be caused by cross-reactivity from sensitization to mite tropomyosin.

PE17-10 Clinical correlation of antigen-specific IgE/IgG4 ratio in milk protein allergy

Chun-Min Kang1,2), Kuan-Hua Chu1), Ya-Chiao Hu1), Hsin-Hui Yu1), Jyh-Hong Lee1), Li-Chieh Wang1), Yu-Tsan Lin1), Yao-Hsu Yang1),Bor-Luen Chiang1) (Department of Pediatrics, National Taiwan University Hospital, Taiwan1); Department of Laboratory Medicine, National Tai-wan University Hospital, Taiwan2))

Background:Milk protein is one of the most frequently reported allergen in young children’s food allergy. Most patients with milk allergy wouldeventually outgrow the symptoms after grow-up and could tolerate intake of milk, termed oral tolerance. Previous studies have suggested thatantigen-specific serum IgG4 might play an important role in the development of oral tolerance, by antagonizing the effect caused by IgE and mastcells, and therefore keep the individual free from symptoms despites the presence of IgE. We hypothesized that antigen-specific IgE/IgG4 ratiocould have better clinical correlation than IgE or IgG4 levels only.Methods: The cases were enrolled from November, 2017 till now. Sera from pe-diatric patients with milk protein allergy were collected and tested for IgE and IgG4 levels of milk protein as well as component proteins (alpha-lactalbumin, beta-lactoglobulin and casein) using commertial kits (ImmunoCAP). Control samples were collected from those who tolerate milk pro-tein intake, either with high milk IgE (> 0.35 kU/L) or low IgE. The IgE/IgG4 ratios were calculated and all data were statistically analyzed. Re-sults: Sixteen samples were collected from patients with milk protein allergy and 26 from asymptomatic (15 with high milk-specifc IgE). The IgE/IgG4 ratios were significantly higher in allergic group, with p-values < 0.001 for milk protein and all component proteins. The statistical signifi-cances are greater than those using IgE or IgG4 alone as markers. We used the data to plot ROC curves, and found that IgE/IgG4 ratios have thelargest overall area under curve (AUC) for milk protein and all the component proteins compared with IgE or IgG4. For alpha-lactalbumin, the dif-ference between AUCs of IgE/IgG4 ratio, IgE and IgG4 reached statistical significance. Conclusion: Antigen-specific IgE/IgG4 ratios give betterclinical correlation in milk protein allergy than IgE or IgG4 levels. Of all component protiens tested, IgE/IgG4 ratio of alpha-lactalbumin most dis-tinctly differs between allergic and asymptomatic groups.

187

PosterSession

PE17-12 Thermal effect on hen’s egg white and quail egg white proteins and analysis of cross-reactivity in young children

Jeongmin Lee1), Purevsan Gantulga2), Kyunguk Jeong2), Se-Ah Jeon2), Sooyoung Lee2) (Department of Pediatrics, Yonsei University Wonju Collegeof Medicine, Republic of Korea1); Department of Pediatrics, Ajou University School of Medicine, Republic of Korea2))

Background: Hen’s egg allergy is most common cause of food allergy in Korean children. This study aimed to identify thermal effect on hen’s eggwhite (EW) and quail egg white (QE) proteins and their cross-reactivity in young children.Methods: Sera from the seven patients who had an im-mediate type hen’s egg allergic history and the concentration of serum specific IgE to hen’s egg white (EW-sIgE)>10 kU/L, ovomucoid (OM-sIgE)>0.35 kU/L and ovalbumin (OVA-sIgE)>0.35 kU/L by ImmunoCAP were collected. We produced crude extracts of raw-EW, -QE, water boiled(100°C, 15min)-EW, -QE, oven baked (180°C, 20min)-EW, commercially baked (45°C, 12h then slowly increased to 110°C, 12h)-EW extracts. SDS-PAGE was performed and pooled sera were tested with each extracts by an enzyme linked immunosorbentassay (ELISA) inhibition test. Further,oral food challenge (OFC) were performed. Results: Patients with median age of 18 months were enrolled. The median concentrations of EW-sIgE,OM-sIgE and OVA-sIgE were 35.7 (IQR 21.0-38.7) kU/L, 21.6 (IQR 12.4-26.2) kU/L and 17.1 (IQR 11.4-24.5) kU/L, respectively. Protein bands fromraw EW were identified at 14, 28, 34, 40, 52, and 69 kDa. All protein bands were considerably diminished in commercially baked EW, whereas 52-and 69-kDa bands were stable by water boiling and oven baking. Inhibition ELISA showed that pre-incubation of sera resulted in a profound de-crease in IgE binding to boiled (50%, 0.072 ug) and raw (50%, 0.422 ug) EW and moderate decrease to boiled QE (20%, 0.087 ug) and raw QE (20%,0.583 ug), indicating allergenic cross-reactivity. Meanwhile, very little decrease in IgE binding to commercially baked EW extract (20%, 27.38 ug)was shown. Two of 3 EW-anaphylaxis patients had passed OFC using commercially baked EW. The one who had presented anaphylaxis to com-mercially baked EW could pass QE-OFC partially (5ea). Conclusion: This study identified moderate cross-reactivity between QE and HE andhome cooking hardly alter its allergenicity in children. Commercially baked EW can be safer choice.

PE17-13 Hemocyanin is not a major allergen in a cohort of probable shrimp-allergic Chinese children

Maco Cheuk Yin Lam, Sze-Yin Agnes Leung, Yee Yan Christine Wai, Yat Hin Nicki Leung, Gary Wong, Ting Fan Leung (Department of Paediat-rics, The Chinese University of Hong Kong, Hong Kong)

Background: High molecular weight (MW) allergens in shrimps are less studied compared to other shrimp allergens like tropomyosin. Hemocy-anin, with MW of around 75kDa, is a protein found in hemolymph and cephalothorax of shrimp in abundance and has been suggested as a clini-cally relevant shrimp allergen in challenge-proven shrimp-allergic patients. This project aimed to investigate the IgE sensitization pattern tohemocyanin in a cohort of Chinese children. Method: Children aged 7- 11 years were recruited from primary schools in Hong Kong under theEuroPrevall-INCO study. Skin prick test (SPT) against shrimp and house dust mite (HDM) was performed, and sIgE against shrimp and HDMwas measured by ImmunoCAP. Collected sera were blotted against protein extract from the giant tiger prawn Penaeus monodon (Pm) by West-ern Blot to screen for IgE binding towards shrimp allergens. Samples showing positive ～75 kDa bands were then selected to blot against nativehemocyanin from the hemolymph extracted from fresh Pm to evaluate its IgE reactivity. Results: A total of 52 children were recruited and cate-gorized into four groups based on history of allergic reaction to shrimp, SPT and sIgE results: (1) allergic group with probable shrimp allergy (n=12); (2) allergic group with history of reactions to shrimp but negative sIgE to shrimp (n=11); (3) non-allergic group without history of allergic reac-tion to shrimp but positive SPT and/or sIgE to shrimp (n=9); and (4) HDM-sensitized controls (n=20). In the Western Blot against Pm extract, seraof four subjects from group 1 showed mild IgE binding towards protein sized 70-80 kDa while all sera from groups 2-4 were tested negative. How-ever, no IgE-binding protein could be probed when these four samples were tested against hemolymph from Pm. Conclusion: Our preliminary re-sults suggest that hemocyanin is not a major allergen among this Chinese cohort. However, further studies are needed to validate our findings.The possible role of hemocyanin in shrimp allergy should also be further investigated in other cohorts of shrimp-allergic patients.

PE17-14 Structure of sensitization to food extracts and molecules in Dnipro (Ukraine)

Kateryna Gashynova, Viktoriia Voloshkina, Eugenia Dytyatkovska (Occupational Diseases and Clinical Immunology, SE Dnipropetrovsk MedicalAcademy Ministry of Health of Ukraine, Ukraine)

Background: The structure of food hypersensitivity may vary between different age groups (G) and regions. The aim was to investigate thestructure of sensitization to food extracts and molecules of animal origin in patients with any signs of allergy and compare different age groups inDnipro region (Ukraine). Study population. 990 symptomatic males and females with any clinical signs of allergy were separated into G in accor-dance with age: G 1 (2-6, n=220), G 2 (7-12, n=222), G 3 (13-18, n=89), G 4 (19-25, n=69), G 5 (26-45, n=291), G 6 (46+, n=99). Methods: Medical history,specific serum IgE to allergen extracts and molecules (ALEX test). Results: The most common allergens were: In G1: Sal s (37.73%); Equ c_meat(23.18%); Gad m (18.18%); Bos d_meat (15.00%); Ory_meat (11.82%); Cyp c 1 (11.82%); Gal d_white (11.82%); In G2: Sal s (33.78%); Equ c_meat (23.42%);Gad m (25.68%); Cyp c 1 (12.16%); Ory_meat (10.81%); In G3: Sal s (33.71%); Equ c_meat (23.60%); Gad m (16.85%); Ory_meat (13.48%); Bos d_meat(12.36%); Ost e (10.11%); In G4: Sal s (20.29%); Gad m (17.39%);Equ c_meat (15.94%); In G5: Sal s (34.36%); Gad m (15.46%); Equ c_meat (12.30%); In G6:Sal s (38.38%); Gad m (22.22%); Equ c_meat (9.09%). Percentage of hypersensitivity to Gal d 1, 2, 3 strongly correlates with Gal d white, unlike Gal d4. Gal d 5 only moderately correlates with Gal d_yolk. There is no any correlation between Bos d meat and Bos D 6. The correlation between Gadm and Gad m 1 is moderate. Conclusions: 1. Pattern of sensitization to food animal allergens is different in different age groups in Dnipro region. 2.The most common food animal allergens for all ages are Sal s; Equ c_meat; Gad m. 3. The percentage of sensitized patients is not the same in ac-cordance to specific IgE to extracts and molecules.

188

PosterSession

PE17-15 Two commercial Gal d 1 specific IgE assays show major differences in specificity and accuracy, with potential clinical implica-tions

Shinya Yoshihara, Motoko Nakayama, Yoshihide Terashi, Koryo Nakayama, Manabu Miyamoto, Yusuke Ando, Yuji Fujita, Masaya Kato,Shigemi Yoshihara (Department of Pediatrics, Dokkyo Medical University, Japan)

Background: Component-resolved diagnostics (CRD) is increasing in routine examinations. CRD is clinically applied taking advantage of the char-acteristics of each component. Therefore, the antigenicity and purity of the components used for CRD are important. Ovomucoid(OVM) is themost routinely used CRD in Japan. Purification of OVM is difficult, and it is reported that lysozyme(LYZ) was contaminated in commercially avail-able purified OVM. The purity of OVM used in a commercially available specific IgE test kit was examined using anti-OVM and anti-LYZ mouse-human IgE chimeric antibodies. Methods: For this purpose, two allergen-specific mouse-human chimeric monoclonal antibodies were used, eachcomprising the antigen-specific variable domain from a mouse monoclonal antibody and the constant part of the heavy chain of human IgE. Theantibodies reacted specifically with Gal d 1 and Gal d 4, respectively, and could be measured with the specific and total IgE assays of both assayplatforms. Results: Both the ImmunoCAP and IMMULITE Gal d 1 assays displayed good dilution linearity for the anti-Gal d 1 chimeric ab. How-ever, a clear difference between these assays was observed when anti-Gal d 4 chimeric IgE antibody was applied to the two Gal d 1 assays. Whilenegative results (<0.1 kUA/L) were obtained with all 6 dilutions of the Gal d 4 IgE antibody in the ImmunoCAP assay, as expected, positive re-sults ranging between 5.6-61.9 kUA/L were obtained with IMMULITE Gal d 1 assay, demonstrating that this assay detects not only Gal d 1 spe-cific IgE but also Gal d 4 specific IgE. Conclusions:We show in this study that both ImmunoCAP and IMMULITE Gal d 1 sIgE assays display fa-vourable dilution linearity properties but that the IMMULITE assay may generate false positive results for samples containing IgE antibodies toGal d 4, presumably as a result of impurity of the Gal d 1 preparation used. Additionally, while the ImmunoCAP Gal d 1 sIgE assay was found ac-curately quantify Gal d 1 specific IgE, the IMMULITE assay appeared to overestimate the Gal d 1 specific IgE concentration 4-fold on average.

PE17-16 Does topical anesthesia affect the interpretation of diagnostic skin testing to food allergens in children

Nattasasi Suchamalawong1), Naruporn Tosirisuk2), Pantipa Chatchatee2), Narissara Suratannon2) (Division of Allergy and Immunology, Departmentof Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thailand1); Division of Allergy and Immunology, Department of Pediat-rics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thailand2))

Background: Skin prick test (SPT) is an important diagnostic test in children with suspected food allergy. Application of topical anesthesia hasbeen considered to reduce the pain of the procedure, but there is still limited data on the vasoconstrictive effect on wheal and flare response. Weconducted this study to determine the effect of topical anesthesia on wheal and flare size of SPT to food allergens in young children. Methods: Inthis experimental within-patient study, children aged 10 months to 5 years with a history of sensitization to food allergens were recruited. We ap-plied eutectic mixture of local anesthetic cream on one arm then performing SPT with food allergen on both arms. Wheal and flare size on botharms were evaluated and compared in a non-inferiority fashion. Results: Eighteen children with the age of 10 months to 49 months (median age 27months) were recruited. Wheal size on topical anesthetic cream -treated arm was not significantly smaller compared to non-treated arms for foodallergens and histamine (mean difference; 0.13 mm, 95%CI; -0.35 to 0.61 and mean difference; -0.11 mm, 95%CI; -0.67 to 0.45 respectively). However,flare size of food allergens on topical anesthetic cream -treated arm was significantly reduced (mean difference; -2.56, 95%CI; -3.69 to -1.44). Conclu-sions: The use of topical anesthesia did not significantly interfere with wheal size and interpretation of SPT result to food allergens. Applyingtopical anesthesia is a potential method to reduce pain in young children undergoing SPT with food allergens. This study was approved by theEthical Committee, Research affairs, Chulalongkorn University. IRB No.419/59. Keywords: food allergy; skin prick tests; topical anesthesia

PE17-17 Effects of reducing the amounts of food allergens in the home environment on allergen sensitization

Fumiya Yamaide1), Chikao Maeda2), Aya Yoshikawa2), Masayuki Mikuriya2), Noriko Sato1), Taiji Nakano1), Yoshikuni Katsura2), Masahiro Imanishi2),Naoki Shimojo1) (Department of Pediatrics, Graduate School of Medicine, Chiba University, Japan1); Duskin Co., Ltd. R&D, Japan2))

Background: The importance of percutaneous sensitization in the development of food allergy has been recognized. Reducing the amounts offood allergens in the home environment may lead to the prevention of the development and exacerbation of food allergies. Aim: The aim of thisstudy was to investigate whether the reduction of allergens in a house of a patient with food allergies by the cleaning intervention of a specializedcleaning contractor would affect their food allergies. Methods: Study subjects were children under 5 years of age with hen’s egg allergy withatopic dermatitis attending the pediatric department of Chiba University Hospital (recruited between January and March 2018). Participantswere divided into two groups (group A: specialist cleaning intervention group and group B: general sweeping guidance group). Allergens in housedust were measured, and allergen sensitization and other outcomes were evaluated at the beginning and end of the study (one year later). Thisstudy was approved by the ethics review of Chiba University School of Medicine, and written consent were obtained from all children’s families.Results: Nineteen pairs of patients and their families participated in this study. 2 pairs withdrew their consent due to family circumstances. Atthe beginning of the study, the amounts of egg allergen were slightly higher in group A, and the mite sensitization and PO-SCORAD were slightlyhigher in group B. At the end of the study, egg white IgE levels tended to be lower in group A. Instead of comparing between groups, we exam-ined the association between allergen amounts and sensitization. Although there was no correlation between the amounts of egg allergen and eggwhite IgE levels, there was a significant positive correlation between changes in the amounts of egg allergen in the dust and changes in egg whiteIgE levels. Conclusion: This study could not detect any differences in outcomes between intervention methods, but there may be a positive corre-lation between changes in food allergens in dust and changes in the degree of allergen sensitization.

189

PosterSession

PE17-18 Probability curve for infant hen’s egg allergy

Yutaka Takemura1), Norihiro Inoue1,2), Tomoyuki Arima1), Hiroki Masumi1), Koji Yamasaki1), Megumi Nagai1), Keisuke Sugimoto1) (Department ofPediatrics, Kindai Hospital, Japan1); Department of Pediatrics, Osaka-Minami Hospital, Japan2))

Background: Although the usefulness of the probability curve has been widely reported in the diagnosis of food allergy, there are few studies re-lated to it in infants. Method: We analyzed hen’s egg oral food challenge(OFC) performed on infants under 12 months of age. The food are ana-lyzed using boiled eggs for 20 minutes, using the results of a test that gave 1/4 or more of whole egg. Result:We analyzed 117 OFC. Participantshad a median age (range) of 10.5 months (6-12 months) and 81 boys (69%). All had never consumed eggs before the OFC. For specific IgE (sIgE),the median egg white (range) was 9.0 (0.3-69.2) kUA/L and the OM was 0.35 (0.09-25.2) kUA/L. When the probability curve was created, egg whitecould not draw a sigmoid curve, but OM could draw a sigmoid curve. Cut-off values were 8.4 kUA/L for egg white and 0.75 kUA/L for OM.Receiver-operating characteristic analysis showed that the OM test had a larger area under the curve (AUC, 0.55) compared with the cashew test(AUC, 0.79). A positive decision point (PDP) based on at least 95% clinical specificity was calculated for the OM test. The PDP was 6.4kUA/L andgave a clinical sensitivity of 30% and specificity of 96%. Discussion and Consideration: In infancy OFC using boiled eggs, the probability curveusing OM is more useful than egg white. In particular, when the OM is 0.75 kUA/L or less, it is desirable to conduct active testing. It may also leadto the prevention of egg allergy.

PE17-19 Evaluation of the allergenicity and induction ability for oral tolerance of ω5-gliadin-deficient Hokushin wheat (1BS-18) in a wheatallergy rat model

Yukinori Yamada1), Tomoharu Yokooji1,2), Naoki Ninomiya1), Takanori Taogoshi1), Eishin Morita3), Hiroaki Matsuo1) (Department of PharmaceuticalServices, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan1); Department of Frontier Science for Pharmacother-apy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan2); Department of Dermatology, Faculty of Medicine, Shi-mane University, Japan3))

Background: There are many patients suffering from allergy to wheat, however, curative treatments for wheat allergy have not been estab-lished. We developed hypoallergenic wheat, Hokushin wheat line lacking ω5-gliadin (1BS-18) which is a major allergen for wheat-dependentexercise-induced anaphylaxis. In this study, we evaluated the allergenicity such as anaphylactic elicitation ability and sensitization ability as wellas induction ability for oral tolerance of 1BS-18. Methods: Allergenicity of 1BS-18 was evaluated using rats sensitized with ω5-gliadin, Hokushingluten or 1BS-18 gluten intraperitoneally. IgE-mediated systemic anaphylaxis was evaluated by measuring changes in rectal temperature for 30min after intravenous challenge with ω5-gliadin or the test glutens in unsensitized rats or rats sensitized with ω5-gliadin or the test glutens. Toevaluate the induction ability for oral tolerance of 1BS-18, rats were subcutaneously sensitized with Hokushin gluten 2 days after the nal oral ad-ministration of 1BS-18 gluten daily for 5 days. Results: In ω5-gliadin-sensitized rats, intravenous challenge with ω5-gliadin or Hokushin glutensignificantly decreased the rectal temperature at 30 min after challenge while challenge with 1BS-18 gluten did not reduce the rectal tempera-ture. Furthermore, intravenous challenge with ω5-gliadin significantly decreased the rectal temperature in rats sensitized with Hokushin glutenor 1BS-18 gluten. However, the reduced degree observed in 1BS-18 gluten-sensitized rats was smaller than that in Hokushin gluten-sensitizedrats. The induction ability for oral tolerance of 1BS-18 is currently under examination. Conclusion: 1BS-18 elicited no allergic reaction in ω5-gliadin-sensitized rats and had less sensitization ability for ω5-gliadin than that of Hokushin wheat.

190

PosterSession

Poster Session 18Food allergy-clinical aspects 1

PE18-2 Combinations of anaphylaxis symptoms in oral food challenges

Naoto Otake1), Tomoyuki Asaumi1), Noriyuki Yanagida1), Sakura Sato2), Motohiro Ebisawa2) (Department of Pediatric, National Hospital Organiza-tion, Sagamihara National Hospital, Japan1); Department of Allergy, Clinical Research Center for Allergology and Rheumatology, National HospitalOrganization Sagamihara National Hospital, Japan2))

Background: Oral food challenges (OFCs) are necessary to diagnose food allergies; however, these tests can cause anaphylaxis. No data regardingthe combinations of anaphylaxis symptoms have been reported. This study aimed to clarify the combinations of anaphylaxis symptoms in OFCs.Methods: We perform stepwise OFCs, in other words we select the amount of food that patients eat according to their severity. The followingwere retrospectively analyzed in our OFCs that tested for four kinds of food (cow’s milk, hen’s egg, peanut, and wheat), which were performed be-tween April 2014 and March 2019: patients’ characteristics, combinations of anaphylaxis symptoms, percentage of severe reactions, and timetaken to manifest obvious symptoms. We investigated differences in anaphylaxis symptoms among each type of food. Results: We performed6485 OFCs for four kinds of food (cow’s milk: 1,999 cases, hen’s egg: 2419 cases, peanut: 875 cases, and wheat: 1189cases). Four hundred and thirtyanaphylaxis cases (milk: 200 cases, hen’s egg: 105 cases, peanut: 70 cases, wheat: 55 cases) of 2065 positive results of OFCs (positive rate is 32%)were analyzed. The median age of the patients with anaphylaxis was 4.8 (interquartile range [IQR]: 3.06.7) years. Three hundred and fifty-eightcases (83%) had a history of immediate reaction to each food. The medians of the specific IgE values of milk, egg white, peanut, and wheat were50.7 (IQR: 22.2112.5), 30.1 (IQR: 11.656.2), 41.8 (IQR: 13.188.7), and 67.2 (IQR: 24.4249.5) kUA/L, respectively. Severe symptoms developed in 47 of 430cases (11%), the detail of cases is 19 cases for cow’s milk, 13 cases for hen’s egg, 8 cases for peanut and 7 cases for wheat. The most frequent combi-nation of anaphylaxis symptoms was“respiratory and skin”(80%). Combinations of symptoms, including gastrointestinal symptoms, were morefrequent in cases involving hen’s egg and peanut than in cases involving milk and wheat (p<0.05). Conclusion: The most frequent combination ofanaphylaxis symptoms was“respiratory and skin.”Anaphylaxis symptoms vary according to the type of food.

PE18-3 Predictor of the buckwheat challenge test results: a retrospective observational study in Japan

Naoki Kajita, Koichi Yoshida, Shoko Yokoyama, Keiko Hirao, Masami Narita (Department of Allergy, Tokyo Metropolitan Children’s Medical Cen-ter Japan)

Background: Buckwheat (BW) is one of the major food allergens and the leading cause of food-induced anaphylaxis in Japan. The standardmethod for diagnosing food allergies is the oral food challenge (OFC). However, when BW allergy is suspected, food avoidance is frequently cho-sen without performing an OFC due to concerns about anaphylaxis. BW-specific IgE values are used to assess BW allergy but their utility is lim-ited. Fag e 3 was recently reported as a BW component associated with OFC results, but its clinical utility has not yet been widely tested. Objec-tive: The aim of this study was to identify factors which may be useful as predictors BW OFC results. Methods: A single center, retrospective,observational study was performed at Tokyo Metropolitan Children’s Medical Center. The records of patients who underwent BW OFC betweenApril 2017 and January 2020 were enrolled. Patients were classified into two groups according to OFC results. Patients with a negative OFC re-sult with total intake < 80g were excluded. The baseline characteristics of the two groups were compared. Univariate analysis was done using theMann-Whitney U test or the Fisher’s exact test. The receiver operative characteristic (ROC) analysis was used to determine single point that si-multaneously maximizes sensitivity and minimizes specificity. Results: In total, 37 patients aged 46-173 months (median 89 months) were ana-lyzed, 10 (27.0%) of whom showed objective symptoms during their OFC. Symptomatic patients had a significantly higher BW-s IgE/total IgE ra-tio than asymptomatic patients (p<0.001), but the total IgE (median concentration: 492 vs. 1380 IU/mL, p=0.139) and BW-s IgE (9.38 vs. 3.58 kUA/L, p=0.130) did not differ significantly between the groups. Receiver operator characteristic (ROC) analysis showed that the BW-s IgE/total IgEratio had a larger area under the curve (AUC, 0.885) than BW-s IgE (AUC, 0.667). The statistically optimal cut off was 0.0058 for the BW-s IgE/to-tal IgE ratio, which corresponded to a clinical sensitivity and specificity of 90.0% and 81.5%, respectively. Conclusions: The BW-s IgE/total IgE ra-tio may be a useful predictor of BW OFC results.

PE18-4 Analysis of the appropriate timing to introduce egg white to children with egg yolk triggered food protein-induced enterocolitissyndrome

Yohei Watanabe, Hideyuki Sakai, Satoru Kumaki (Department of Pediatrics, Sendai Medical Center, Japan)

Background: In Japan, reports of hen’s egg yolk triggered food protein-induced enterocolitis syndrome (EY-FPIES) have been increasing. Thesepatients should eliminate egg yolk until tolerance acquisition, but it remains to be elucidated when egg white should be introduced to them.Meth-ods: To optimize the timing of introducing egg white to these patients, we compared the results of egg white oral food challenge tests (OFC) be-fore tolerance acquisition of egg yolk (BT-group; n=5) with those after the acquisition (AT-group; n=10). Results: Percentages of subjects withpositive egg white specific IgE (EW-sIgE) were 40% in each group. All of the subjects did not exhibit delayed abdominal reactions to the eggwhite. In BT-group, all two subjects with positive EW-sIgE exhibited immediate reactions with 0.5g and 2g egg white OFC, respectively. Further-more, one of them not only exhibited a respiratory symptom induced by OFC using 0.5g egg white, but also had an increasing level of EW-sIgEwith age, and delayed tolerance acquisition for egg yolk. In AT-group, 2 of the 10 subjects with positive EW-sIgE exhibited immediate reactionswith 2g OFC and with consuming whole egg products at home, respectively. Conclusion: There seems to be no risk of delayed abdominal reac-tions to egg white in EY-FPIES patients. Thus, especially in patients negative with EW-sIgE, one should consider the early introduction of eggwhite regardless of tolerance acquisition status of egg yolk. Also, for patients who have both an increasing level of EW-sIgE with age and a de-layed tolerance acquisition of egg yolk, we should pay much attention to the risk of severe immediate reactions.

191

PosterSession

PE18-5 Prediction of severe peach allergy reaction combining peach allergen component specific IgE antibodies in Japanese childrenand adolescents

Yusuke Ando, Yoshihide Terashi, Shinya Yoshihara, Koryo Nakayama, Manabu Miyamoto, Masaya Kato, Yuji Fujita, Motoko Nakayama,Hironobu Fukuda, Shigemi Yoshihara (Department of Pediatrics, Dokkyo Medical University, Japan)

Background: To predict severity of peach allergy specific IgE antibody (sIgE ab) were measured to peach allergen components in patients diag-nosed peach allergy.Method: Twenty-seven patients diagnosed a peach allergy at the Department of Pediatrics, Dokkyo Medical University Hos-pital between October 2012 and September 2017 were enrolled. Diagnosis was made on the basis of a convincing history of allergic reactionswithin 2 hours after ingesting peach and the presence of sIgE Abs to crude peach extract (>0.1 UA/mL) in the sera of patients. SIgE ab to peachcrude extract, Pru p 1, Pru p 2, Pru p 3, Pru p 4, Pru p 7, Japanese cedar pollen and alder pollen were measured in sera from the subjects by Im-munoCAP. We classified into two groups by their allergy symptoms: The local reaction group (LR) including only mucosal symptoms in oral and/or throat, and systemic reaction group (SR) that includes 10 cases of anaphylaxis. Results: SIgE ab titers of Pru p 1, Pru p 4 and alder pollen in LRwere significantly higher than those in SR. sIgE to Pru p 7 was significantly higher in SR than in LR. Few sensitizations to Pru p 2 and Pru p 3were detected. We examined whether allergy severity could be evaluated by combining the peach allergen components. When Pru p 7 was nega-tive, and either Pru p 1 or Pru p 4 was positive, none of the 12 patients experienced anaphylaxis. When Pru p 7 was positive, and either Pru p 1 orPru p 4 was negative, there were 9 cases of anaphylaxis out of 12. Conclusion: These findings suggest that sensitization to Pru p 1 and/or Pru p 4is associated with local symptoms and sensitization to Pru p 7 associated with systemic reaction and anaphylaxis. To predict severity of peach al-lergy in childhood and adolescence, it is useful to measure SIgE ab to Pru p 1, Pru p 4 and Pru p 7 in combination.

PE18-6 Risk factors for moderate to severe allergic reactions in oral food challenges

Kazuki Sato1), Azusa Nakamura1), Shuichi Suzuki1), Hiroko Watanabe1), Minako Tomiita1), Yohei Kawasaki2), Yuki Shiko2) (Department of Pediatrics,Shimoshizu National Hospital, Japan1); Clinical Research Center, Chiba University Hospital, Japan2))

Background: In the previous study, we investigated the risk factors of anaphylaxis in oral food challenge tests. Because anaphylaxis rate was aslow as 6 percent, accurate estimates were difficult using Bayesian analysis. As a result, the estimated odds ratio was not sufficiently reliable.Therefore, we increased the number of cases and focused on moderate to severe allergic reactions, which had a higher incidence, and estimateditems related to the allergic reactions. Method: Single-center retrospective study was performed. Patients hospitalized in Shimoshizu NationalHospital for food challenge tests from 2016 to 2018 were recruited. Patients over 20 years old were excluded. Twelve clinical parameters such asage, gender, specific IgE value, and complication of asthma or atopic dermatitis were examined. The severity of allergic reactions was evaluatedwith a score of four degrees, 0: none, 1: mild, 2: moderate and 3: severe, anaphylaxis, based on the Japanese Pediatric Guideline for Food Allergy2016. Bayesian statistic models for moderate to severe allergic reaction in oral food challenges were constructed and validated. Results: Nine hun-dred and sixty-one patients were analyzed, excluding 95 due to age or data deficiency. Challenged foods were heated chicken eggs, milk, wheat(noodles), peanuts and others in that order. There were 348(34.8%) patients with score of 2 or 3. Patients with lower intake tended to have more se-vere allergic reactions. The final model that best fit data for was Hierarchical Bayes model. Results show that moderate to severe allergic reac-tions increases: (i) for higher milk specific IgE, (ii) for dividing into five times every 20 minutes (v.s. 3 times every 40 minutes), (iii) for completeelimination diet. The odds ratio of each predictor were 16.3(from10 to 100UA/mL), 1.8 and 1.9, expectedly. Conclusion: In oral food challenges,food type, challenge protocol, and complete elimination diet were strongly involved in moderate to severe allergic reactions not only specific IgE.

PE18-7 Predictive factors of walnut allergy: a retrospective observational study in Japan

Ayano Nishimoto, Masami Narita, Koichi Yoshida, Keiko Hirao, Shoko Yokoyama (Department of Allergy, Tokyo Metropolitan Children’s MedicalCenter, Japan)

Background:Walnut is the most common tree nut allergen in Japan. The oral food challenge (OFC) is the definitive method of diagnosing walnutallergy but is time-consuming and potentially dangerous. Dietary elimination of walnuts based on factors, such as a past history of immediate re-actions after ingesting walnut, detection of walnut-specific IgE antibodies, and/or positive skin prick test results, is usually recommended. Objec-tive: This study aimed to identify the predictive factors of walnut allergy. Method: The present, single center, retrospective, observational studywas performed at Tokyo Metropolitan Children’s Medical Center. The results of OFC using walnut between January 2017 and January 2020 werereviewed, and the patients were classified based on their results into the walnut-allergy (WA) group or non-walnut allergy (NWA) group, whichincluded patients with a negative OFC result at a total intake 10g or more. The baseline characteristics of the two groups were then compared.Univariate analysis was done using the Mann-Whitney U test or Fisher’s exact test. Regression analysis was used to create probability curves.Results: Forty-four patients aged 37 to 170 months (median age: 77.5 months) were included. Thirty-three patients (75.0%, median age: 79.0months) had a positive OFC result (WA). Skin symptoms were the most frequent symptoms (18 patients), and 17 patients had symptoms in morethan two organs. The WA group showed a significantly higher walnut-specific IgE and walnut-specific IgE/total IgE ratio(p=0.002) than the NWAgroup (p<0.001), but there was no significant difference in the total IgE between the groups (median concentration: 806 vs. 1020 IU/ml, p=0.915).Receiver operator characteristic (ROC) analysis showed that walnut-specific IgE had a larger area under the curve (AUC, 0.926) than the walnut-specific IgE/total IgE ratio (AUC, 0.802). The statistically optimal cut off was 3.89 for walnut-specific IgE, which corresponded to a clinical sensitiv-ity and specificity of 84.8% and 90.9%, respectively. Conclusions: The walnut-specific IgE and the walnut-specific IgE/total IgE ratio are usefulpredictors of walnut OFC results.

192

PosterSession

PE18-8 Diagnosis of bean sprout allergy with anaphylaxis shock

Yasuhiko Koga1), Masakiyo Yatomi1), Haruka Aoki-Saito1), Takeshi Hisada2) (Department of Respiratory Medicine, Gunma University GraduateSchool of Medicine, Japan1); Gunma University Graduate School of Health Sciences, Japan2))

Background:Many cases of soy-milk allergy has been reported as pollen food allergy syndrome (PFAS). However, few English literatures reportson sprouts anaphylaxis despite the growing diversity of food cultures worldwide. Methods: We experienced two cases of bean sprout-inducedanaphylaxis at Gunma University Hospital. Specific IgE against Gly m4, Bet v1, white birch pollen, and soybean were examined. Prick-to-pricktest was also examined using fresh and boiled bean sprout. Results: No cases were showing negative Gly m4 or Bet v1 IgE. Specific IgE againstwhite birch showed positive results in all cases. Bean sprout-induced allergy was thought to be type 2 allergy. Consistently, all cases showed nega-tive or low levels of soybean IgE. The most important issue is that one of two cases resulted in anaphylaxis shock facing consciousness disorder,hypotension, and hypoxia. Conclusion: Bean sprout-induced anaphylaxis is thought to be caused by the sensitization to Bet v1 of white birch,which has cross-reactivity with PR-10 protein, Gly m4 of soybean. Bean-sprout anaphylaxis should be careful to be a cause of anaphylaxis shock.

PE18-9 Basophil activation test for milk and egg allergy in children with atopic dermatitis

Yoon Hee Kim1), Young Suh Kim1), Younhee Park2), Soo Yeon Kim1), Hye Yung Yum3), Kyung Won Kim1), Myung Hyun Sohn1) (Department of Pedi-atrics, Yonsei University College of Medicine, Republic of Korea1); Department of Laboratory Medicine, Yonsei University College of Medicine, Re-public of Korea2); Department of Pediatrics, Seoul Medical Center, Republic of Korea3))

Purpose: In children with food allergy (FA) accompanying with atopic dermatitis (AD), excavating of causative food allergen is more fastidiousbecause a large number of AD can entail a positive sensitization with high specific IgE (sIgE) without clinical allergic symptoms. We evaluate thebasophil activation test (BAT) in children with milk or egg allergy with AD.Methods: A total of 89 children who were suspicious adverse reactionby food from August, 2017 to March, 2018 were enrolled. We measured sIgE levels (UniCAP) and performed BAT (BUHLMANN CAST) to cowmilk and egg white at the same time. We compared the diagnostic performance using diagnostic accuracy and reliability of sIgE and BAT by De-long methods and also compared them according to the presence of AD. The diagnostic reliability of BAT was compared in subgroups (with ADvs. without AD) by bootstrapping method. Results: Analysis were completed in 75 children for milk allergen (26 children with milk allergy) and 85children for egg allergen (42 children for egg allergy). The sIgE and the percentage of CD60+ basophils of both milk and egg were well correlated.The area under the receiver operating characteristic (AUC) of sIgE (0.701) for milk allergy was increased greater when the BAT was combined(0.805; p=0.029). When accompanying with AD, the AUC of BAT (0.924) for milk allergy was greater than that of sIgE (0.701). The AUC of BAT formilk allergy was greater in children with AD (0.924) than those without AD (0.666; p=0.004). Conclusions: BAT can be a useful diagnostic toolcombined with sIgE in children with milk allergy. Especially when accompanying AD, BAT can be a surrogate marker for milk allergy.

PE18-10 Factors associated with passing small dose milk oral food challenges

Hiroaki Taniguchi1,2), Satoshi Hirase1,2), Masashi Hara1,2), Yukari Koshiba1,2), Mizuka Kaji1,2), Kumiko Itani1,2), Kanako Nakano1,2), Kunitaka Ota1,2),Motohiro Ebisawa3) (Department of Pediatrics, Konan Medical Center, Japan1); Department of Pediatrics, Rokko Island Hospital, Japan2); ClinicalResearch Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan3))

Background: Since 2017, when conducting small dose milk oral food challenge (OFC), our facility switched from using unheated to heated milkand introduced smaller dose challenges with longer intervals.Methods:We sought to investigate the factors influencing results of milk OFC andits safety by conducting a retrospective chart review of patients receiving small dose milk OFC (milk protein<660mg) who have previously beeneliminating milk from their diet at our facilities from 2012 to 2020. Most of the patients before 2017 were challenged with unheated milk, whereasheated milk was used from 2017. Between positive and negative OFC, we compared patient characteristics, whether the milk was heated or un-heated, and amount of milk protein challenged. Results: Fifty patients underwent their first small dose milk OFC during the study period, ofwhich 18 patients were positive (36%). When comparing patient characteristics, those who passed the OFC had significantly lower milk- andcasein-specific IgE values (median 8.0 vs 13.2 kUA/L for milk, and 6.3 vs 18.7 kUA/L for casein, p values 0.026 and 0.009, respectively). Significantlyhigher rate of patients who were negative received heated milk OFC (91% vs 50%, p=0.004), which was introduced to all patients from 2017. Ma-jority of unheated milk OFC was positive (75%), whereas heated milk had much lower rate (24%). There were no statistical differences observedin the patients’ age, gender, history of immediate reactions to milk, and rate of comorbid allergic diseases. Amount of milk protein challenged andchallenge interval was not significantly associated. Multivariate analysis revealed that lower milk-specific IgE values and receiving heated milkOFC was significantly associated with passing small dose milk OFC, but not amount of milk protein or challenge intervals. Conclusion: Lowermilk-specific IgE values and receiving heated milk OFC was associated with passing small dose milk OFC. Using heated milk to conduct smalldose milk OFC might be beneficial from both viability and safety viewpoint.

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PosterSession

PE18-11 Clinical manifestations and safety of oral food challenge using boiled egg yolk

Kei Uneoka1), Satoshi Horino1), Masato Nihei1), Haruka Aki1), Hiroshi Kitazawa1,2), Katsushi Miura1) (Department of Allergy, Miyagi Children’s Hospi-tal, Japan1); Division of Pediatrics, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Japan2))

Background: Hen’s egg is one of the most common allergens encountered in childhood, furthermore, egg white (EW) is considered to be more al-lergenic than egg yolk (EY). Although many studies have reported on oral food challenge (OFC) using EW, it has not been reported whether OFCusing boiled EY without EW is safe. This study aimed to clarify the safety of OFC using boiled EY and to determine the clinical characteristics ofOFC-positive patients. Methods: This retrospective analysis reviewed data from patients who underwent OFC using boiled EY from January2013 to July 2019 at the Miyagi Children’s Hospital. These participants had either experienced an immediate reaction induced by hen’s egg or hadelevated serum specific IgE in response to EW. Before performing the OFC, EW was carefully removed from EY immediately after boiling. Weexamined the detailed results of the OFC and factors including age, history of anaphylaxis, allergic comorbidities and serum level of specific IgE(EY, EW, and ovomucoid). Results: Of 560 patients, 14.6% had positive OFC results but only one patient needed adrenaline intramuscular injec-tion. Age, respiratory complication rate, serum total IgE and specific IgE (EY, EW, ovomucoid) levels were significantly higher in the OFC posi-tive group. Abdominal, skin and respiratory symptoms were respectively observed in 70.7%, 56.1% and 23.2% of OFC positive patients. Conclu-sion: OFC using boiled EY showed a low rate of severe symptoms. Further, OFC positive patients were more likely to show abdominal symp-toms.

PE18-12 Oral food challenges for the diagnosis of food allergy, real life experience from Mexico

Joaquin A Pimentel, Elsy M Navarrete, Blanca E Del Rio, Enrique E Castelán (Department of Allergy and Immunology, Hospital Infantil deMéxico, Mexico)

Background: The prevalence of food allergy in children varies according to the region studied and the method of investigating it. In the case ofLatin America, studies are scarce and are mostly based on questionnaires and self－reports, overestimating the actual prevalence. Methods: Co-hort study conducted over a period of 24 months. Patients with allergic comorbidities from 6 months to 18 years and suspected food allergy with arestriction diet were included. Clinical data were collected and skin prick tests, atopy patch tests, prick to prick and oral challenges were per-formed according to symptoms. The oral challenges were open or double－blind placebo controlled, reaching 3g of protein and with 30－minuteintervals between feedings, the recipes were prepared with products with low lipid intake and mixed with ingredients that masked the flavor.Prior to the dietary challenges, a validation of the recipes was performed using the triangle test; which allowed to ensure the correct blinding. Re-sults: 175 patients were included, 61.1% were men and 38.9% were women, 83.4% had allergic rhinitis, 57.7% asthma, 29.1% atopic dermatitis and2.3% eosinophilic esophagitis. The total of suspicious foods was 375, a total of 4517 individual tests were performed. The most frequently reportedsymptoms for each food were immediate (66.5%), no-immediate (37%) and both in 8%. 149 oral challenges were performed, of which 18 were posi-tive. The food most frequently implicated in positive oral challenges was milk, with a total of 10 positive challenges followed by egg with 4. Thesymptoms most frequently associated with the positive challenge were cutaneous and immediate followed by gastrointestinal. The inclusion of357 foods in the diet was successfully achieved. Conclusions: This is the fifth study performed in Mexico on oral challenges and food allergy andthe one that includes the largest number of oral challenges. By means of the oral challenge, only 4.8% of food allergy was confirmed, with milk be-ing the most frequent food. A total of 357 foods were successfully reintroduced to the diet.

PE18-13 A feasibility study of oral-food-challenge in non-IgE-mediated gastrointestinal food allergies in infants by long-term and incre-mental methods

Koji Nishimura, Miori Sato, Hiroya Ogita, Tomoyuki Kiguchi, Yoshitsune Miyagi, Yusuke Inuzuka, Kenji Toyokuni, Makoto Irahara,Fumi Ishikawa, Shigenori Kabashima, Kiwako Yamamoto Hanada, Tatsuki Fukuie, Ichiro Nomura, Yukihiro Ohya (Allergy Center, National Cen-ter for Child Health and Development, Japan)

Background: Diagnosis of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs) is depends on the results of the oral food challengetests (OFCs). However, the safe OFC protocol for non-IgE-GI-FA has not been developed yet. We have developed an OFC protocol that allows forlong-term and incremental doses.Methods: Eighty-two patients with non-IgE-GI-FAs hospitalized for OFCs to confirm remission of disease at Na-tional Center for Child Health and Development (NCCHD) from 2014 to 2019 were retrospectively investigated. The OFC inclusion criteria is thatthe diagnosis was clear from the clinical history and symptoms with improvement after withdrawal of the suspected trigger food, and differentialdiagnosis has been excluded. OFCs performed to confirm the diagnosis or at home were excluded. The protocol for the oral challenge test was setfor four days for food-protein-induced enterocolitis syndrome (FPIES) and nine days for food-protein-induced enteropathy (FPE) and allergic proc-tocolitis (FPIAP). The patient took 1/50 of the target amount on the first day, and gradually increased to the target amount on the fourth day.FPE and FPIAP continued to take the target dose on days 5-9. Results:We collected a total of 82 OFCs of non-IgE-GI-FAs, including 30 with acuteFPIES, 15 with chronic FPIES, 17 with FPE, and 20 with FPIAP. The number of OFCs was increasing during the study period. Milk was the mostcommonly challenged food (63%), followed by soy (12%) and rice (7%). Positive reactions occurred in 10%, all of which were FPIES and were treat-able with infusions of extracellular fluids (four patients) and intravenous glucocorticoids (three patients). The period from initial diagnosis to OFCof FPE group was significantly longer compared to that of acute FPIES group (8.0 months [5.25-21.5] vs. 26.0 months [13.0-30.0], P<. 01) and chronicFPIES group (8.0 months [6.0-10.5] vs. 26.0 months [13.0-30.0], P<. 01). Conclusions: Our data suggest that our OFC protocol for non-IgE-GI-FAswas safe and feasible.

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PosterSession

PE18-14 Prediction of negative results of oral food challenges by antigen-specific IgE values

Daisuke Takeishi, Yuji Iimura, Mariko Mikami, Ichiro Matsumoto, Akira Kono (Department of Pediatrics, Jouhoku Hospital, Japan)

Background: In our department, we conducted Oral food challenges (OFC) in inpatient and outpatient setting. If antigen-specific IgE (sIgE) isclass 2 or lower (Egg white specific IgE≦14.0IUA/mL. IMMULITE 3gAllergy), we have performed OFC in outpatient setting. We thought thatOFC could be performed more safely if the results of OFC could be predicted by sIgE values. Therefore, we examined whether sIgE values couldpredict the OFC result in eggs, milk and wheat allergic children. Methods: 517 children who conducted OFC between June 2013 and December2019 were included. Eggs, milk and wheat allergy, 313, 142 and 62 children, respectively, were included. We retrospectively investigated eggs,milk and wheat allergic children who underwent OFC. We set the cutoff value by sIgE, and calculated the sensitivity, specificity, positive predic-tive value (PPV), negative predictive value (NPV) and negative likelihood ratio (LR-). Results:When egg white sIgE<14.8IUA/mL was cut off, sen-sitivity was 85.8%, specificity was 85.5%, PPV was 80.2%, NPV was 89.8%, LR- was 0.17. When ovomucoid sIgE<7.73IUA/mL was cut off, sensitivitywas 85.0%, specificity was 78.0%, PPV was 72.5%, NPV was 88.4%, LR- was 0.19. When milk sIgE<2.78IUA/mL was cut off, sensitivity was 80.0%,specificity was 57.5%, PPV was 54.3%, NPV was 82.0%, LR- was 0.35. When casein sIgE<2.05IUA/mL was cut off, sensitivity was 83.6%, specificitywas 57.5%, PPV was 55.4%, NPV was 84.8%, LR- was 0.29. When wheat sIgE<1.81IUA/mL was cut off, sensitivity was 73.5%, specificity was 60.7%,PPV was 69.4%, NPV was 65.4%, LR- was 0.44. When gluten sIgE<1.45IUA/mL was cut off, sensitivity was 79.4%, specificity was 67.9%, PPV was75.0%, NPV was 73.1%, LR- was 0.30. When ω-5 gliadin sIgE<0.44IUA/mL was cut off, sensitivity was 85.3%, specificity was 85.7%, PPV was 87.9%,NPV was 82.8%, LR- was 0.17. Conclusion: It was suggested that OFC results could be predicted by using the above cut-off. In order to implementOFC more safely, we thought it would be necessary to continue using OFC with reference to the above cut-off.

PE18-15 Effect of frequency of hen’s egg ingestion on the succeeding oral food challenge test

Toshiyuki Takagi, Yuki Okada, Kosei Yamashita, Chihiro Kunigami, Mayu Maeda, Toshinori Nakamura, Taro Kamiya, Takanori Imai,Katsumi Mizuno (Department of Pediatrics, Showa University School of Medicine, Japan)

Purpose: Hen’s egg (HE) allergy children can reduce the risk of failing the oral food challenge (OFC) by avoiding the complete elimination and in-taking a portion of HE. It is unclear if the frequency of the intake impacts on the following OFC result.Method: This retrospective study includeschildren who had passed 1/32nd of HE OFC and undertook the succeeding OFC with 1/8th of HE at our hospital between May 2019 and January2020. At the second OFC, we interviewed how many times in a week the children ingested 1/32nd of HE and calculated the total number of theingestion by multiplying the frequency by the duration from the first OFC. Logistic regression analysis was applied to evaluate the impact whichwas adjusted using age, gender, complications of allergic diseases, past history of anaphylaxis, total IgE levels, and egg white and ovomucoid spe-cific IgE levels. The results are shown as the median (interquartile). Result: 74 children aged 2 (1-4) years were included. 45 (61%) were male. 19(25.7%) had experienced anaphylaxis. Their specific IgE of egg white and ovomucoid was 13.1 (4.3-31.3) IU/mL and 6.74 (1.60-15.6), respectively.The proportion of successful OFC was 65 (87.8%). The total number of the ingestion was 113 (77-213) times, which had no significant associationwith OFC results (OR 0.98 [0.94-1.01], aOR 0.96 [0.92-1.01]). However, children who kept eliminating HE had 40% higher odds for failing OFC thanthose intaking at least once a week (OR 1.39 [1.20-1.58], aOR 1.41 [1.21-1.65]). Conclusion: This study shows children confirmed their safe intakedoses should not keep eliminating completely.

PE18-16 Evaluation of risk factors and safety of oral food challenges of a very small portion of an egg

Aiko Honda, Mayu Maeda, Yuki Okada, Toshinori Nakamura, Taro Kamiya, Takanori Imai (Department of Pediatrics, Showa University School ofMedicine, Japan)

Background: Aiming to induce tolerance in children with a severe egg allergy, we have performed oral food challenges (egg OFC: eOFC) since2019 of a very small portion of an egg. We analyzed the results of the eOFC and evaluated risk factors associated with positive results and safety.Method: The participants were pediatric patients with an egg allergy who had undergone eOFCs from February 2019 to March 2020. The testswere performed with single doses of 1/100 of a whole egg. Severity of induced symptoms, treatment, and the final decision whether to continueabstention were recorded. Based on details from the medical records including characteristics and baseline specific Immunoglobulin E (IgE) levelsof the patients we retrospectively evaluated the factors related to the results. For statistical comparisons between the two groups, we used thechi-square test and the Mann-Whitney U-test; multivariate analyses were analyzed by logistic regression. Results are shown as the median (25-75th percentile). Result: Ninety-four patients underwent eOFC. The median age was 34 (range, 23-52) months old. The patients included 61 males(64.9%), and 24 (25.5%) had a history of anaphylaxis to eggs. 24 (25.5%) patients had atopic dermatitis, and 23 (24.5%) had asthma. The median levelof non-specific IgE was 460.5IU/mL (201-1079.8), specific IgE to egg whites was 50.7 UA/mL (21.0-89.7) and to ovomucoid was 39.5 UA/mL (18.0-64.0. Positive OFC results were obtained in 44 patients (46.8%), including 36 (38.3%) gastrointestinal symptoms, 16 (17.0%) skin symptoms, 6 (6.4%)respiratory symptoms, and 2 (3.6%) cardiovascular symptoms. Eleven (11.7%) patients were presented with anaphylaxis. Treatments adminis-tered were H1-antihistamines in 11 patients (11.7%), inhaled short-acting beta-2-agonists in 3 (3.2%), and intramuscular adrenaline injection in 6(6.4%). One patient exhibiting a severe reaction required an additional adrenaline injection. Multivariate analysis revealed that no significant fac-tors were related to a higher risk of positive eOFC results. Conclusions: There was no correlation factor with the positive results in the eOFC.Considering that some patients showed critical symptoms during the tests, we continued to have problems for safety.

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PosterSession

PE18-17 Risk factors for multiple-nut allergies in patients with peanut allergy

Kazutaka Nogami, Mayumi Matsunaga, Shingo Yamada, Miyuki Hoshi, Kana Hamada, Keigo Kainuma, Mizuho Nagao, Takao Fujisawa (AllergyCenter, National Hospital Organization Mie National Hospital, Japan)

Background: Patients who experienced severe allergic symptoms after ingesting peanuts for the first time often fear allergies to other nuts thatthey have never eaten. Physicians also sometimes advise them to avoid all kinds of nuts. However, not all patients with peanut allergy (PA) de-velop allergies to other nuts. To preclude unnecessary avoidance, correct diagnosis is important. To that end, we aimed to identify risk factors formultiple-nut allergies in patients with PA. Methods: This was a retrospective observational study. We enrolled patients who had confirmed PAbased on a positive oral food challenge (OFC) or a history of peanut-elicited immediate symptoms. Allergies to 4 major nuts/seeds (walnuts, cash-ews, almonds, sesame) were determined based on a positive OFC or a history of immediate allergic symptoms after ingesting the correspondingnut. The subjects were divided into 2 groups: peanut-only allergy (P) and multiple-nut allergies (M). The following data were retrieved from elec-tronic charts: age, gender, allergy to other foods, comorbid allergic diseases such as asthma, atopic dermatitis (AD) and allergic rhinitis, total IgEand specific IgE to peanuts and other nuts. Fisher’s exact test and the Mann-Whitney U-test were used to analyze for associations betweenmultiple-nut allergies and possible risk factors. Results: A total of 42 patients were recruited: 27 were in Group P, and 15 were in Group M. TotalIgE was significantly higher in Group M than in Group P. The proportion of AD patients who needed strong topical steroids to control the diseasewas significantly higher in Group M than in Group P. The prevalence of other food allergies, including to eggs, milk and wheat, were also higher inGroup M than in Group P. Accordingly, the number of food allergens in Group M was significantly higher than in Group P. PA patients who hadegg and/or milk allergy had 6.2-fold increased odds of having multiple-nut allergies. Conclusions: Higher total IgE, severe AD and other food al-lergies were risk factors for multiple-nut allergies in patients with PA.

196

PosterSession

Poster Session 19Food allergy-clinical aspects 2

PE19-2 Eosinophilic gastroenteritis treated with targeted two-elimination diet in a child

Masaaki Doi1), Aya Sasaki1), Akiko Masaki1), Ryouta Yoshida1), Kumiko Takagi1), Yasutaka Matsubara1), Yasuko Furuichi1), Shinnosuke Tsuji2),Tomoko Takano2) (Department of Pediatrics, Higashiosaka City Medical Center, Japan1); Department of Pediatrics, Osaka General Medical Center,Japan2))

Background: Eosinophilic gastroenteritis (EGE) is a rare inflammatory disease characterized by eosinophils infiltrating into the gastrointestinal tract. Itsrarity renders the optimal treatment unclear. Although an etiological association of EGE with food antigens has been reported, allergen-specific immuno-globulin (Ig) E or atopy patch and skin prick test results do not always correlate with causative foods. Therefore, empiric multiple FED is used to treatEGE; however, this strategy is time-consuming and may cause a nutrition problem, which in turn decreases the patient’s willingness toward treatment.We describe a pediatric case of EGE treated with targeted two-FED. Case: An 8-year-old boy was diagnosed with food allergy to various food antigens,including wheat and soy, in infancy. He completely abstained from consuming the causative foods until the age of 2 years. However, soy and cow’s milkwere resumed at the age of 2 and 4 years, respectively. When wheat diet was started, he experienced watery diarrhea 35 times/day for 4 years. Endo-scopic examination revealed eosinophilic infiltration of >40/HPF in the ileum and colon. According to a detailed interview covering food consumption his-tory, symptoms, and their temporal relationships, wheat and soy were considered as the most probable causative foods and two-FED was initiated. Simul-taneously, oral administration of fexofenadine, suplatast tosilate, and montelukast was started. The diarrhea resolved quickly after therapy initiation. Oncompletely eliminating soy and wheat for 4 weeks, soy was resumed, followed by wheat. After resuming wheat ingestion, fecality deteriorated. A roughelimination of wheat (e.g., elimination of bread) was reinitiated, after which the diarrhea resolved rapidly again. Based on this clinical course, wheat wasconsequently established as the causative food. Therefore, wheat was resumed and discontinued recurrently according to the fecality. After 11 weeks ofinitiating treatment and despite consuming any wheat product, the child no longer had diarrhea. Endoscopic examination after 12 weeks revealed patho-logical improvement. Conclusion: FED can be effective for treating EGE, and detailed interviews can aid in minimizing the number of eliminated foods.

PE19-3 Analysis of pollen-specific IgE levels that induce pollenfood allergy syndrome in children

Masaya Kato, Shinya Yoshihara, Yoshihide Terashi, Koryo Nakayama, Manabu Miyamoto, Yusuke Ando, Yuji Fujita, Motoko Nakayama,Shigemi Yoshihara (Department of Pediatrics, Dokkyo Medical University, Japan)

Background: Allergens with cross-reactivity to fruits/vegetables and pollen are demonstrated in pollenfood allergy syndrome (PFAS). For exam-ple, Rosaceae fruit allergens are cross-reactive with those of alder and birch, and tomato allergens cross-react with Japanese cedar. However, inclinical practice, few patients with cedar pollinosis also show allergy to tomatoes. We re-examined the potential relationship between allergies tofruits/vegetables and pollen sensitization in children.Methods:We re-assessed medical records of 136 patients aged 318 years with known fruit/vegetable allergies who visited our department between January 2016 and December 2019. The relationship between symptoms after eatingfruits/vegetables and specific IgE antibody levels to alder, Japanese cedar, ragweed, and orchard grass pollen was examined using informationfrom the patients’ medical records. Results: The pollen-specific IgE positivity rate (positivity rate 0.70 UA/ml) was 91% for alder, 99% for Japa-nese cedar, 71% for ragweed, and 73% for orchard grass. The most frequent allergy foods (in decreasing order) were peach, kiwi, apple, melon,pineapple, strawberry, and tomato. Among 136 patients with PFAS, we determined whether there were differences in the pollen-specific IgE lev-els between children with and without allergies to Rosaceae fruits, tomatoes, cucurbit fruits, and pineapples. For Rosaceae fruits, the pollen-specific IgE levels of alder and ragweed were significantly higher in children with these allergies. For tomatoes, significant differences were ob-served for orchard grass only. For cucurbit fruits, significant differences were found for ragweed and orchard grass. Pineapple did not signifi-cantly affect pollen-specific IgE levels. Conclusion: We found evidence of cross-reactivity for tomato and orchard grass allergens. The cross-reactive allergens for fruits/vegetables and pollen detected here may differ from those of previous reports.

PE19-4 Integrated analysis of genomics and metabolomics in childhood food allergy resolution

Haerin Jang, Mi Na Kim, Jung Yeon Hong, Yoon Hee Kim, Myung Hyun Sohn, Kyung Won Kim (Department of Pediatrics, Severance Hospital,Republic of Korea; Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Republic of Ko-rea; Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medi-cine, Republic of Korea)

Background: The natural history of childhood food allergy (FA) occasionally involves a spontaneous resolution of symptoms after years of adver-sity. However, the underlying mechanism behind FA resolution is poorly understood, making prediction challenging. In this study, we examinedthe metabolomic and genetic profile of childhood FA to investigate the metabolic footprint and identify distinctive patterns between patients withresolved and persistent FA.Method:We applied LC-MS untargeted metabolomic profiling with serum samples of 20 egg allergy patients and 20controls. FA patients were consisted of 10 patients with resolved symptoms and 10 with persistent symptoms, where samples for analysis werecollected at the time of diagnosis and after confirmed resolution or matching time progress in persistent patients. We also collected genotype datafrom all subjects to investigate metabolite-SNP association using metabolomic quantitative trait loci (mQTL) analysis. Results: Compared to pa-tients with persistent FA, patients with resolved FA had a marked decrease in metabolites related to eicosanoids and arachidonic acid metabo-lism at the time of FA diagnosis. Especially 8,15-DiHETE, lipopoxin A4, and Prostaglandin H2 were significantly decreased in resolved FA. mQTLanalysis revealed that genetic variations in genes related to lipoprotein metabolism, including LDLRAD3, ST6GALNAC3, ELP1 , and TUSC3 , areassociated to these metabolites, suggesting an underlying genetic effect. Cortisol and cortisone levels were also significantly lower in resolved FAin association to genetic variations in ADCY3 and OPHN1 . Comparing FA with controls, a difference in sphingolipid levels were observed be-tween groups. Conclusion: Children with resolving FA have a unique metabolomic profile compared to persistent FA and its association with re-lated genetic variants provides insights on underlying mechanisms. Our results demonstrate the promise of using genetic variants resulting in dif-ferences in the metabolome to predict the trajectory of childhood FA.

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PosterSession

PE19-5 Retrospective review of food allergic children in a tertiary allergy centre in Hong Kong

Ting Fan Leung, Agnes Sze Yin Leung, Noelle Anne Ngai (Department of Paediatrics, The Chinese University of Hong Kong, Prince of WalesHospital, Hong Kong)

Background: Food allergy is the leading cause of anaphylaxis in children. Our territory-wide study in 2006-2007 revealed shellfish, egg, fish, cow’smilk and peanut to be the leading causes of adverse food reactions (AFR) in Chinese preschoolers. However, there was limited hospital-based dataon childhood food allergy in southern China. This study reviewed the spectrum of food allergy among children attending a pediatric allergy clinicin Hong Kong. Methods: This retrospective study identified 689 patients with AFR who were referred to our allergy clinic in 1999-2018. Theirdemographics, medical history and AFR details were recorded prospectively into our registry. Skin prick test (SPT) was performed with crudeextracts of eight inhalants and 15 foods. Food allergy was diagnosed in patients with AFR and positive SPT (wheal ≧3 mm larger than negativecontrol) to the same food. Differences in proportions between groups were analysed by Pearson χ2 or Fisher exact test. Results: 323 (46.9%) pa-tients were allergic to a total of 486 foods, with the leading foods being egg (n=171), peanut (n=82), fish (n=70), cow’s milk (n=65), shellfish (n=48),wheat (n=36) and soy (n=14). The number of food-allergic patients increased from 50 in 1999-2003 to 203 in 2014-2018. Among 323 patients, 88(27.2%) had a history of food-induced anaphylaxis according to WAO/NIAID guideline. We observed that highest proportion of peanut (45.8%) andwheat (41.7%) allergic patients had history of anaphylaxis. Concordance between AFR and SPT positivity was high for milk, fish, egg, wheat andpeanut (p<0.0001), weak for soy (p=0.031), but poor for shellfish (p=0.210). When analyses was restricted to immediate-type (≦2 hours) symptoms,we found concordant AFR and SPT results only to fish (p=0.023). Conclusions: Our tertiary centre receives increasing number of food allergy re-ferrals over the past 20 years. Instead of shellfish, egg and peanut are the leading causes of food allergy in this hospital-based cohort. As SPT isconcordant only with immediate-type AFR to fish, oral food challenges are needed to establish food allergy diagnosis in most patients.

PE19-6 Major triggers of food allergy and food-induced anaphylaxis in recent 10 years in Korea: a single hospital retrospective study in-cluding all ages

Eunjoo Lee1), Sooyoung Lee2), Kyunguk Jeong2), Yoo Seob Shin3), Young-Soo Lee3), Young-Min Ye3) (Department of Pediatrics, Inje University Hae-undae Paik Hospital, Republic of Korea1); Department of Pediatrics, Ajou University School of Medicine, Republic of Korea2); Department of Al-lergy and Clinical Immunology, Ajou University School of Medicine, Republic of Korea3))

Background: There is no recent study of food allergy (FA) covering all ages in Korea. We performed this study to identify major triggers of foodallergy and food induced anaphylaxis including all ages in a single tertiary hospital in Korea.Methods: A retrospective medical record review anddetailed analysis were performed on patients of all ages diagnosed with immediate-type FA between March 2008 and February 2018 in Ajou Uni-versity Hospital. Results: A total of 4,680 cases of FA among 2,733 patients were reported. The distribution of onset ages of the first FA symptomwas as follows: 45.3% below 2 years, 16.2% in 2-6 years, 5.5% in 7-12 years, 4.0% in 13-18 years, 16.9% in 19-40 years, 10.4% in 41-65 years, and 1.8%above 65 years of age. The 10 major causative foods were hen’s eggs (17.2%), cow’s milk (16.7%), wheat (8.6%), crustaceans (8.5%), fish (4.6%), wal-nuts (4.4%), pork (3.2%), peanuts (3.2%), shellfish (3.0%), and peach (2.2%). The culprits ranked from 11th to 20th were as follows: soybean, apple,chicken, buckwheat, beef, kiwi, almonds, perilla seeds, tomato, and squid. Food-induced anaphylaxis was reported in 29.2% of all cases. The top 10triggers of food-induced anaphylaxis in children were cow’s milk, hen’s eggs, wheat, walnuts, peanuts, buckwheat, crustaceans, fish, pine nuts andperilla seeds, and those in adults were wheat, crustaceans, fish, shellfish, pork, beef, squids, buckwheat, chicken, soybean and peanuts. The foodswith the highest proportion of anaphylaxis was buckwheat (60.0%), followed by barley (47.4%), pine nuts (45.2%), wheat (42.8%) and pork (35.3%),whereas in adults, it was the highest upon exposure to pupa (72.7%), followed by peanuts (57.1%), buckwheat (56.5%), wheat (51.3%) and mango(50.0%). Conclusion: The main causative foods of FA and anaphylaxis differ between children and adults. This study would provide detailed infor-mation on the causes of FA by age group in Korea, for better understanding of major items for food labeling and the prevention of anaphylaxis.

PE19-7 Prevalence of food allergy in staff members of Fukuoka National Hospital, Japan

Akiko Sugiyama1,2,3), Reiko Kishikawa1,3), Koki Okabe1,3), Takehito Fukushima1,3), Nanae Kimura2), Kaoru Kojima3), Makiko Oda3), Satoshi Honjo3),Makoto Yoshida3), Mai Honda4), Hiroyuki Murota4), Masutaka Furue5) (Department of Allergy, Fukuoka National Hospital, Japan1); Department ofDermatology, Fukuoka National Hospital, Japan2); Department of Clinical Research, Fukuoka National Hospital, Japan3); Department of Dermatol-ogy, Nagasaki University Hospital, Japan4); Department of Dermatology, Kyushu University Hospital, Japan5))

Background: Food allergy is potentially fatal not only for children but also for adults. Prevalence and related factors of food allergy (FA) in adult-hood has been little investigated in Japan, however. Subjects and Method:We distributed a self-administered questionnaire (Kijima A, Murota Het al. 2013) to 417 persons working at Fukuoka National Hospital (19-82 years old) to ascertain history and clinical course of allergic diseases includ-ing FA and exacerbating factors as well as family history of the allergic conditions. The response was obtained from 357 (86%; mean [SD] age, 41.3[13.0] years). Result: The prevalence of FA was 5.0% (n=19; mean [SD] age, 43.5 [11.6] years), and those of allergic rhinitis (AR), atopic dermatitis(AD), and bronchial asthma (BA) were 33, 7.0, and 5.0%, respectively. The average age of onset of FA was 16.0±12.8 years, and 16 cases had devel-oped after infancy. Persons with AR, with paternal history of BA, with maternal history of AD, or with sibling having AD or FA were more likelyto have FA. No relapse of FA after remission was reported from 15 cases with previous history of FA in contrast to other allergic diseases. Con-clusion: Family history of allergic diseases is important for the risk of FA in adults. Further studies are required to corroborate the present find-ings.

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PE19-8 Incidence of allergic reactions in elementary, junior high, and high schools in Gunma Prefecture from 2015 to 2019

Takaharu Inoue1,2), Hisako Yagi1), Satoshi Yamada1), Koichiro Sato1), Yutaka Nishida1), Hirokazu Arakawa1), Takumi Takizawa1) (Department of Pe-diatrics, Gunma University Graduate School of Medicine, Japan1); Department of Pediatrics, Public Tomioka General Hospital, Japan2))

Background: Schools need to deal with the incidence of allergic reactions among students because of an increase in the prevalence of food aller-gies among children. Methods: To analyze allergy cases at school and delineate issues to be resolved, we investigated the data collected by theGunma-prefectural Committee for Food Allergy at schools and analyzed the symptoms, causes, and actions for allergic reactions that occurred atschools in Gunma, Japan from 2015 to 2019. Results: The total reported cases were 157, of which there was an annual increase of 20, 29, 25, 42, and41 cases for each year. Cases included more boys (61%) than girls. There were 68 (43.3%), 72 (45.8%), and 17 (10.8%) cases in elementary, juniorhigh, and high schools, respectively. In total, 38.2% of cases presented their first episode of an allergic reaction at school. Food-dependent exercise-induced anaphylaxis or its suspected cases accounted for 40% of the total, which increased annually. Among the 157 cases, 10 were served regularlunch from which they avoided allergen food themselves, and four were served with wrong ones whose original lunch was to be devoid of allergenfoods. The doctor-written direction form for allergy was not filled in 26 cases, and the prescribed rescue medicine was not brought in by sevencases. The number of EpipenⓇ prescriptions, which increases yearly, reached 814 in 2019. EpipenⓇ was used in 15 cases in total. Rescue treatmentwas delayed in three cases because it was waived until their guardians arrived at school. Conclusion: The incidence of allergic reactions atschools increased annually in Gunma. The incidence was relatively more frequent in junior high schools. Some cases were likely difficult to predictand prevent, but there were preventable incidences such as the absence of direction files, wrongly served lunch, and self-avoidance of causativefood. Preventive actions are required for these issues.

PE19-9 Sensitization to gibberellin-regulated protein in hinoki cypress pollen is associated with severity of peach allergy

Nobuyuki Maruyama1), Sakura Sato2), Kyotan Sho1), Cerrone Cabanos1), Motohiro Ebisawa2) (Graduate School of Agriculture, Kyoto University, Ja-pan1); Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan2))

Background: Gibberellin-regulated proteins (GRPs) are suggested to be linked to a cypress pollen/food-associated syndrome.Methods: 1) Eighty-six patients with peach allergy were enrolled in this study and classified into two groups: the local reaction group (LRG, 52 patients) and the sys-temic reaction group (SRG, 34 patients). Anaphylactic reactions were observed in 8 patients of SRG; 2) GRPs were purified from peach flesh andHinoki cypress pollen using cation-exchange and gel filtration chromatography. Purified GRPs were confirmed by mass spectrometry; 3) The lev-els of specific IgE (sIgE) to GRPs in patients’ sera were measured using a fluorescent enzyme-linked immunosorbent assay. A pool of serum sam-ples with known sIgE by Immuno-CAP analysis were used to establish a standard curve and the results were expressed as ELISA-based kilo-units per liter (kUE/L). Results: The sensitization frequencies to Hinoki cypress GRP and Pru p 7 in SRG were 52% and 50%, respectively. All pa-tients with anaphylactic reactions in SRG were sensitized to both Hinoki cypress GRP and Pru p 7 (1.1 kUE/L to 66.5 kUE/L, with a median of 19.7kUE/L for Hinoki cypress GRP; 2.8 kUE/L to 77.5 kUE/L, with a median of 8.7 kUE/L for Pru p 7). Significant correlations in sIgE levels betweenHinoki pollen GRP and Pru p 7 in SRG were observed (rlog=0.940). When comparing the sIgE levels between LRG and SRG, the AUC values of theROC analysis to Hinoki cypress GRP (0.715, 95% CI 0.635-0.862) were similar to those for Pru p 7 (0.748, 95% CI 0.635-0.862). Conclusion: sIgE levelsto Hinoki pollen GRP are relevant to those to Pru p 7 in peach allergic patients with a systemic reaction. *This study was supported by a grantfrom the Food Safety Commission, Cabinet Office, Government of Japan (Research Program for Risk Assessment Study on Food Safety, No 1807).

PE19-10 Increase in food protein-induced enterocolitis syndrome caused by solids: a case study

Daisuke Shigeta1), Takayuki Nakazawa1), Tatsuya Yoda1), Machiko Hosoya1), Hisako Yagi2), Takumi Takizawa2) (Department of Pediatrics, SakuCentral Hospital Advanced Care Center, Japan1); Department of Pediatrics, Gunma University Hospital, Japan2))

Purpose: Food protein-induced enterocolitis syndrome (FPIES) is a type of allergy that mainly presents with gastrointestinal symptoms in a non-IgE-dependent manner. In Japan, although FPIES has been reported to be mostly caused by milk, solid food such as hen’s egg yolk have also beenobserved to cause the disease. This is known as solid food FPIES. We have encountered 14 cases of solid food FPIES in our institution and weaimed to report the characteristic features of these cases.Methods: We retrospectively reviewed the medical records of 14 cases diagnosed withsolid food FPIES at our hospital between October 2014 to January 2020. The diagnosis was based on international consensus guidelines. Results:The subjects included 8 boys and 6 girls with a median age of 8 months. They had an average of 2.4 episodes before diagnosis. Symptoms started1 to 4 hours after ingestion of causative food. 8 cases presented with vomiting alone, while 6 cases presented with vomiting and diarrhea. Thecausative food were hen’s egg yolk and wheat in 7 and 2 cases, respectively. The suspected agents in the other 5 cases were scallops, salmon roe,chicken, fish, and cherry. Antigen-specific IgE antibodies were positive in 4 cases. Eight patients experienced repeated symptoms after subse-quent ingestions. Of the 7 cases subjected to oral challenge testing, 5 cases were tested positive. Remission was observed in 2 cases. Conclusion:Solid food FPIES caused by hen’s egg yolk has increased, as seen in 50% of cases in this study. FPIES develops when there is repeated intake ofcausative food even when the patient was initially asymptomatic at the first exposure to such an agent. Its symptoms such as vomiting and diar-rhea are difficult to distinguish from those caused by acute gastroenteritis. It is, therefore, important to suspect FPIES when similar symptomsdevelop after ingestion of a certain food.

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PosterSession

PE19-12 Progression to esophageal eosinophilia in patients with suspected eosinophilic esophagitis or congenital esophageal stenosis

Mariko Shimizu1), Yuichi Kama1,2), Akihiko Shimizu1), Shigeru Nomura1), Akira Nishi3), Masahiko Kato1,2), Yoshiyuki Yamada1) (Division of Allergyand Immunology, Gunma Children’s Medical Center, Japan1); Department of Pediatrics, Tokai University School of Medicine, Japan2); Division ofSurgery, Gunma Children’s Medical Center, Japan3))

Background: Eosinophilic esophagitis (EoE) rarely occurs in infancy and should be distinguished from other diseases of infancy, such as congeni-tal esophageal stenosis (CES) although it is sometimes difficult. This study determined the characteristics of patients suspected to have EoE orCES during infancy who eventually developed esophageal eosinophilia (EE). Methods: We retrospectively reviewed symptoms, histological find-ings, and treatments of infants with early suspicion of EoE or CES who later developed EE (15 per high-power field [HPF]) during follow-up(20052019) at our hospital. Results: This study included five patients (female, n=1; CES, n=2; EoE, n=2; EoE secondary to eosinophilic gastroenteri-tis [EGEEoE], n=1). Initial symptoms were vomiting of solids (n=4) and poor weight gain (n=1). Median age at onset and diagnosis of EE was 6(range 29) and 27 (range 1133) months, respectively, and median peak intraepithelial eosinophil count was 112 (range 48290) per HPF. Two pa-tients with CES were treated with end-to-end esophageal anastomosis, and one was postoperatively treated with a proton-pump inhibitor (PPI).Treatment with PPI was effective in two patients with EoE and one with EGEEoE. Conclusion: Besides EoE, causes of EE may occasionally in-clude CES and EGE. Therefore, long-term follow-up using endoscopy should be recommended in patients with suspected EoE or CES.

PE19-13 Pollen-food allergy syndrome in Japanese children with allergic diseases: a single center study

Azusa Nakamura, Syuichi Suzuki, Kazuki Sato, Minako Tomiita (Department of Pediatrics, National Hospital Organization National ShimoshizuHospital, Japan)

Background: Pollen-food allergy syndrome (PFAS) is caused by cross-allergenicity between pollen and foods such as fruits and vegetables. Theprevalence and clinical characteristics of PFAS in Japanese children with allergic diseases have been unclear.Methods:We conducted a question-naire survey at our center in 2019. Caregivers of children with allergic diseases aged 0-18 years were asked about oral symptoms (OS) followingingestion of raw fruits or vegetables, symptoms of pollinosis, and other 6 6 doctor-diagnosed allergic diseases. Results:We analyzed 273 out of 300responses to the questionnaire. Overall, 72 (26%) patients were considered to have PFAS, reporting OS after ingesting raw fruit or vegetables andhaving symptoms of pollinosis. The prevalence of PFAS was 16% (17/106) in 0-6 years, 32% (35/109) in 7-12 years, and 34% (20/58) in 13-18 years.Patients with PFAS were more likely to be male than those without PFAS (74% vs 58%). In addition, patients with PFAS had more allergic dis-eases than those without PFAS (mean: 2.9 vs 2.2), with a significantly higher diagnosed atopic dermatitis (57% vs 39%), allergic rhinitis (50% vs27%), and allergic conjunctivitis (31% vs 13%). In 86 patients who experienced OS, the most common food that triggered OS was kiwi (45%), fol-lowed by melon (33%), pineapple (24%), watermelon (24%), peach (26%), and apple (12%). The number of reported foods that triggered OS was sig-nificantly higher in the patients who had symptoms of pollinosis during three or four seasons. Conclusion: In our center, approximately one quar-ter of pediatric patients with allergic diseases were estimated to have PFAS with male dominance and more comorbidities of allergic diseases.

PE19-14 Sensitization to hen’s egg during early infancy in a cohort study of Japanese infants with eczema

Mari Takei1), Noriyuki Yanagida2), Sakura Sato1), Yohei Watanabe3), Shigenori Kobayashi3), Hideo Kaneko3), Michimasa Fujiwara3),Wakako Shinahara4), Hiroshi Kido4), Motohiro Ebisawa1) (Department of Allergy, Clinical Research Center for Allergy and Rheumatology, NationalHospital Organization Sagamihara National Hospital, Japan1); Department of Pediatrics, National Hospital Organization Sagamihara National Hos-pital, Japan2); Immune Abnormal Network Group, National Hospital Organization, Japan3); Division of Enzyme Chemistry, Institute for EnzymeResearch, Tokushima University, Japan4))

Background: There are few studies of high-risk infants with eczema where in the development of sensitization to food allergens and food aller-gies have been assessed. The aim of this study was to clarify the risk of sensitization to hen’s egg (HE) in infants with eczema at 1 mo of age andconsider the mechanism of HE sensitization (ES). Methods: In this prospective cohort study, we recruited 1-month-old breastfeeding babies witheczema. We measured their eczema statuses based on scoring atopic dermatitis (SCORAD) and transepidermal water loss (TEWL) at 1, 2 and 4mo(s) and assessed ES at 2 and 4 mos using skin prick test (SPT) and ImmunoCAP system. The cheek [at 1, 2, and 4 mo(s)] and bed mattress (at 2mos) ovalbumin (OVA) levels were measured using a densely carboxylated protein chip. ES was defined as egg white SPT≧3 mm and/or IgE≧0.10 kUA/L; Egg allergy (EA) was defined as a positive result of an HE oral food challenge or clinical history of immediate allergic reaction on con-suming HE. Results: Among 185 enrolled babies, 154 who could be assessed for EA were analyzed. Eighty-one infants (53%) had ES at 4 mo; 24 ofthem had EA. The remaining 73 infants (47%) did not have ES, and none of them developed EA. ES at 4 mo was associated with TEWL at 1 mo[odds ratio (OR) 1.042; 95% confidence interval (CI) 1.0131.072, p＝0.037], the bed mattress OVA level (OR 1.980; 95% CI 1.1403.437, p＝0.046), totalIgE (OR 3.396; 95% CI 1.4188.137, p＝0.035), and OVA IgG1 level (OR 7.385; 95% CI 1.77330.770, p＝0.029). Conclusion: Environmental exposure toHE with skin barrier dysfunction during early infancy seems to be a risk factor for ES. One third of 4-month-old babies with ES developed EA. Onthe other hand, 4-month-old babies without ES had not developed EA.

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PosterSession

PE19-16 An epidemiologic study of oral allergy syndrome and pollen allergy in Japanese university students

Nobue Takamatsu1), Masaru Kubota2), Izumi Hayashidera2), Kumiko Nakai3), Yukie Higashiyama4), Takashi Kusunoki2) (Beppu University, Japan1);Ryukoku University, Japan2); Hagoromo University of International Studies, Japan3); Aichi Shukutoku University, Japan4))

Background: Recent reports from various countries demonstrated an increase of oral allergy syndrome (OAS) in patients with food allergy. In ad-dition, OAS is reported to be complicated with pollen allergy. However, the exact prevalence of OAS with pollen allergy has not been well eluci-dated in adolescents. The aim of the present study is to elucidate the prevalence in Japanese university students.Methods: Our own self-reportedquestionnaire was made after discussion among authors who participated in this study. The questionnaire consisted of questions including posi-tivity of food allergy, if positive, main symptoms especially the presence of OAS, causative foods, and the experience of consultation, the positivityof pollen allergy, if positive, possible causative pollen, and the experience of consultation. Participants were students attending to either Ryukoku,Beppu, Hagoromo International or Aichi Shukutoku universities during April and May in 2019. After excluding the incomplete answers, 1100 stu-dents (male 418, female 682, mean age 19.1 yr) were enrolled. This study was approved by the ethical committee of Ryukoku University. Results:(i) Totally, 221 (20.1%) students had food allergy. Male showed 14.1% positivity, whereas female showed 23.8% (p<0.001). (ii) Among students withfood allergy, 21 males (35.6%) and 84 females (51.9%) had OAS (p=0.032). (iii) Approximately, half students with food allergy consulted the physi-cians, and 87 (39.4%) students were diagnosed as food allergy without any sex difference. (iv) Kiwi, melon, pineapple and peach are representativecausative foods in OAS. The number of causative foods tended to be higher in females. (v) Totally, 587 (53.4%) students had pollen allergy, butthere was no sex difference. (vi) The overall rate of complication of OAS and pollen allergy was 76 (6.9%) students. Discussion: This large scalestudy on OAS and pollen allergy in adolescents clearly indicates high prevalence of both condition. However, since the number of students whoconsulted the physicians is limited, a further study is necessary to delineate“true food allergy”from“food hypersensitivity”.

PE19-17 Changes in the clinical presentation of infants’ food allergies at first onset and the impact of early food introduction in a 9-yearperiod

Kiyotake Ogura1), Kyohei Takahashi1), Noriyuki Yanagida1), Sakura Sato2), Motohiro Ebisawa2) (Department of Pediatrics, National Hospital Organi-zation Sagamihara National Hospital, Japan1); Clinical Research Center for Allergy and Rheumatology, National Hospital Organization SagamiharaNational Hospital, Japan2))

Background: The food allergy (FA) guideline recommends early introduction of weaning food to help reducing baby’s allergy risk. This studywas conducted to clarify the changes in the clinical presentation of food allergies of infants, with a focus on the impact of early introduction.Meth-ods: The retrospective study enrolled patients who had visited our hospital between 2010 and 2018, and their age at the first visit was 24 months.The clinical information of immediate-type allergy-inducing food antigens were extracted from the database and analyzed. Results: A total of 2358participants were included in the analysis. The patients’ age (median, interquartile range) at their first visit to our hospital was 7 (1014) months. Atinitial diagnosis, 41.4% of the participants were suspected to have FA by sensitization, and 57.9% were diagnosed with FA from the history ofimmediate-type allergic symptoms (other causes were implicated in 0.7% of patients). The age at the onset of the first immediate-type allergicsymptoms was 8 (711) months, and the age changed significantly earlier in recent with the year of the first visit (p-trend<0.001). There were 4195antigens registered, and the numbers of hen’s egg (HE), cow’s milk (CM), and wheat (W) allergies were 1512, 1089, and 522, respectively. Dividingthe antigens into two groups based on whether their first hospital visit was before December 2014 or after January 2015, the rate (%) of HE, CM,and W for all antigens in older and recent groups were HE; 34.3 and 39.8, CM; 25.2 and 27.5, W; 11.4 and 14.6, respectively. For HE, a weak correla-tion was detected between the month age of FA diagnosis and the year of the first visit, and the age of diagnosis was significantly delayed (r=0.237, p-trend<0.001). Conclusions:Weaning foods seem to have been introduced earlier for the allergic infants, and the diagnosis of egg allergyseemed to have been delayed over years. Early food introduction might affect these clinical changes.

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PosterSession

Poster Session 20Food allergy-clinical aspects 3

PE20-1 Three-year prognosis of fish allergy in children

Naoko Fusayasu1), Tomoyuki Asaumi1), Hiroaki Taniguchi3), Noriyuki Yanagida1), Sakura Sato2), Motohiro Ebisawa2) (Department of Pediatrics, Na-tional Hospital Organization Sagamihara National Hospital, Japan1); Department of Allergy, Clinical Research Center for Allergy and Rheumatol-ogy, National Hospital Organization Sagamihara National Hospital, Japan2); Department of Pediatrics, Konan Medical Center, Japan3))

Background and Objective: Fish is one of the common causative foods of allergy in Japanese children. However, few studies have reported theprognosis of fish allergy in children. Therefore, we investigated the prognosis of fish allergy in children.Methods: This questionnaire-based studyinvestigated children who had an immediate-type fish allergy. We collected data via two rounds of survey, from August 2016 to February 2017and from August 2019 to February 2020. We included the patients who participated in both surveys. We analyzed patient characteristics, toler-ance acquisition to the fish, and change in specific Immunoglobulin (sIgE) in a span of 3 years. Results: Among the 97 patients who had avoidedfish and participated in the first survey, 59 patients (62%) took part in the second survey. The median age of patients at the first survey was 7years (IQR: 411). Of the included patients, 42 patients (73%) were male, 5 patients (9%) had a history of anaphylaxis to fish, and 32 patients (56%)had atopic dermatitis. The median total IgE level was 1590 (8372535) kU/L. After 3 years, 39 patients (66%) became tolerant to at least 1 fish typeand 9 patients (15%) were tolerant to all the fish types. In this study, horse mackerel was the most common causative fish types. Among 44 pa-tients who had been allergic to horse mackerel, 24 (55%) got tolerant to horse mackerel. The median horse mackerel-sIgE level at the first surveywas significantly lower in tolerant patients than in intolerant patients (1.8 vs. 4.8 kUA/L, p=0.01). The ratio of horse mackerel-sIgE in the secondsurvey to that in the first survey was significantly lower in tolerant patients than that in intolerant patients (0.45 vs. 0.97, p=0.049). Conclusions:Even in cases wherein fish was eliminated because of a history of immediate fish allergy symptoms, more than half of the children became toler-ant to at least 1 fish type. Specific IgE levels may be a good tool to predict the prognosis of fish allergies in children.

PE20-2 An evaluation of the effects of Kakkonto in combination with dietary advice in children with food allergies through a non-randomized controlled trial

Taisuke Kato1), Yasunori Ito1), Takeshi Yamamoto2), Muneyuki Shimizu1), Yoko Adachi1), Makoto Kadowaki2), Yuichi Adachi1) (Department of Pedi-atrics, Faculty of Medicine, University of Toyama, Japan1); Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, Universityof Toyama, Japan2))

Background: In patients with food allergies, oral immune tolerance is induced upon ingestion of the causative food. Kakkonto is a Chinese herbalmedicine used for common colds, but we reported that immune tolerance was induced through use of Kakkonto when administration of causativefood in pathophysiological models of food allergies in mice. Thus, this Chinese medicine may be used as a supportive treatment that is involved inthe acquisition of resistance in humans. This study aimed to evaluate the efficacy and safety of the acquisition of tolerance through administrationof Kakkonto when consuming meals in children with food allergies. Methods: An oral food challenge (OFC) was performed on children with foodallergies. Those who tested positive received kakkonto when they ingested a small amount of causative food in a non-randomized controlled trial.OFC and blood tests were performed at enrollment and 6 months later to confirm changes in triggered threshold protein levels and various anti-body titers. Results: A total of 22 children were enrolled (10 in the oral administration group and 12 in the non-administration group). The thresh-old change (protein equivalent) at 6 months was 378±341 (%) and 547±721 (%) in the oral administration and non-administration groups, respec-tively (p=0.51). Total Immunoglobulin E (IgE) was elevated in 4 children and decreased in 5 (1 child had a missing baseline measurement) in theoral administration group, and elevated in 6 and decreased in 6 in the non-administration group, and there were no significant differences ob-served. Specific IgE was elevated in 0 children, decreased in 9, and unchanged in 1 child in the oral administration group, and elevated in 2, de-creased in 9, and unchanged in 1 child in the non-administration group. Conclusion: Although the obvious superiority of Kakkonto was not dem-onstrated in this study, absence of elevations in specific IgE was observed in many children in the oral administration group. There were also noadverse events due to oral administration observed.

PE20-3 Efficacy of bronchodilators for moderate respiratory symptoms in oral food challenges

Toshinori Kitatsu1), Naoko Fusayasu1), Tomoyuki Asaumi1), Noriyuki Yanagida1), Sakura Sato2), Motohiro Ebisawa2) (Department of Pediatrics, Na-tional Hospital Organization Sagamihara National Hospital, Japan1); Department of Allergy, Clinical Research Center for Allergy and Rheumatol-ogy, National Hospital Organization Sagamihara National Hospital, Japan2))

Background: The Japanese guidelines for food allergy and European Academy of Allergy and Clinical Immunology anaphylaxis guidelines rec-ommend that respiratory symptoms such as repetitive coughs or mild wheezing can be treated with inhalation of bronchodilators alone in oralfood challenges (OFCs) administered by clinical staff experienced in managing anaphylaxis. However, no studies have demonstrated the efficacyof bronchodilators for respiratory symptoms in OFCs. We aimed to evaluate the efficacy of bronchodilators for respiratory symptoms in OFCs.Methods:We retrospectively analyzed subjects whose initial symptoms were moderate respiratory symptoms in OFCs of hen’s egg, cow’s milk,and wheat at our hospital between April 2008 and June 2019. We excluded subjects who had severe respiratory symptoms as initial symptoms orother organ symptoms observed when respiratory symptoms appeared. Results: Five hundred and twenty subjects had moderate respiratorysymptoms as initial symptoms in OFCs of three kinds of food (hen’s egg: 134 subjects, cow’s milk: 214 subjects, wheat: 172 subjects). The medianage of the subjects was 3.7 years. Four hundred and fourteen subjects (80%) had a history of immediate symptoms. The median specific immuno-globulin E (IgE) levels for egg white, milk, and wheat were 19.8, 28.0, and 30.3 kUA/L, respectively. The median specific IgE levels for ovomucoid,casein, and omega-5-gliadin were 10.8, 31.2, and 3.1 kUA/L, respectively. Regarding the initial symptoms, 354 subjects (68%) had repetitive coughsand 225 subjects (43%) had wheezing detectable via auscultation. After all subjects were treated with bronchodilators as the first-line treatment,respiratory symptoms disappeared in 446 subjects (86%). Respiratory symptoms relapsed after the symptoms disappeared in 37 subjects (7%),and adrenaline was required in 2 subjects (0.4%). Meanwhile, among 74 subjects (14%) whose symptoms remained, adrenaline was required in 14subjects (3%). Conclusion: Bronchodilator inhalation is effective for moderate respiratory symptoms in OFCs administered by clinical staff experi-enced in managing anaphylaxis. However, patients must be observed carefully because respiratory symptoms in OFCs may relapse or may notimprove following bronchodilator inhalation.

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PosterSession

PE20-4 Examination of a single administration of 2g of boiled egg white to infants sensitized to egg white in a first-time oral food chal-lenge

Koji Yamasaki1), Yutaka Takemura1,2), Tomoyuki Arima1), Hiroki Masumi2), Megumi Nagai1), Norihiro Inoue3), Keisuke Sugimoto1) (Department ofPediatrics, Kindai University Hospital, Japan1); Department of Pediatrics, Kaizuka City Hospital, Japan2); Department of Pediatrics, National Hospi-tal Organization Osaka Minami Medical Center, Japan3))

Background: Recent studies show that administering an allergen to an infant to ingest from an early stage, 6 months after birth, before sensitiza-tion occurs helps to prevent food allergies. However, the best approach safely feeding suspected allergens to infants already sensitized remainsunclear. Therefore, this study aimed to examine the positive rate and safety of a single oral food challenge (OFC) of 2 g of boiled egg white fed toinfants suspected to have egg allergy. Subjects and Methods: From July 2018 to February 2020, we performed an OFC where 2 g of egg white,boiled for 20 min, was fed to infants aged 618 months, whose egg white-specific IgE (sIgE) levels were 0.7 (UA/mL) and ovomucoid (OM) sIgE lev-els were 17.5 (UA/mL). Results: Overall, 47 infants (35 boys) with a median age of 10 months, and median sIgE levels of (UA/ml) 8.46 and 2.27 foregg white and ovomucoid, respectively. The percentages rate of infants with a history of allergy, were 9 (19.1%), 43 (91.5%), and 3(6.3%), respec-tively. The rate of OFC positive was 9 (19.1%), and the median time to onset of symptoms was 55 min. The Sampson Grade (G) at the time of ap-pearance of symptoms was G1 for 0, G2 for 8, and G3 for 1. No infant was administered adrenaline. Comparison of Area Under the Curve in the Re-ceiver Operating Characteristic ROC curve of the median sIgE value (UA/mL) based on the OFC results revealed that egg white sIgE was 0.518and OM sIgE was 0.673, showing that OM sIgE was more useful. Conclusion: In this OFC, neither the allergic reaction positivity rate nor the se-verity of the reactions was high, and a certain level of stability was maintained To develop a safe and diagnostically efficient OFC method whereboiled egg white is used, OM sIgE may be more effective than egg white sIgE; studies with a larger number of subjects are needed.

PE20-5 Effect of the change in specific immunoglobulin E levels on the result of oral food challenge for patients with egg allergy: a retro-spective observational study

Masaru Kawamura, Moeri Tsuji, Kota Ikari, Takuya Oda, Junichiro Tezuka (Department of Allergy and Pulmonology, Fukuoka Children’s Hospi-tal, Japan)

Background: In clinical situations of food allergy, changes in specific immunoglobulin E (sIgE) levels are often used for assessing the status of sen-sitization. However, there are few reports the change in sIgE levels affects the result of the oral food challenge (OFC). The aim of this study wasto investigate whether the change in sIgE levels can predict the result of the OFC.Methods: This study included patients with hen’s egg allergywho had a positive reaction in the OFC (first OFC) and subsequently took the OFC for the same dose (second OFC) in our hospital from Novem-ber 1, 2014 to November 30, 2019. Between the first OFC and second OFC, the patients consumed eggs at amounts that were lower than theirthreshold twice within a week. We divided the positive group and the negative group based on their allergic reaction in the second OFC, and com-pared the change in sIgE levels. Result: The positive and negative groups comprised 8 and 12 cases, respectively. The median term from the firstOFC to the second OFC was 208 days (range: 115-754). The egg white and ovomucoid sIgE levels decreased significantly more in the negativegroup than in the positive group (median -4.6%/month vs. -0.36%/month, p=0.0048). All cases in which sIgE levels increased had allergic reactionsin the second OFC. Conclusion: The change in sIgE levels can predict the result of the OFC.

PE20-6 The problems with allergen-free hospital food service

Sanae Kishida1), Sachiko Kaburagi1), Kumiko Morita1), Tomo Ishii2), Masayuki Akashi1) (Department of Pediatrics, Keio University Hospital, Japan1);Department of Pediatrics, Tochigi Medical Center, Japan2))

Background: Providing appropriate allergen-free meals for inpatients is extremely important for safety management in hospitals, but there arefew reports on the current state of allergen-free food service. Methods: All medical records of inpatients from December 1-7, 2019 were obtainedfrom Keio University Hospital. We performed a retrospective chart review and analyzed the number of patients and allergenic foods, the occupa-tions of those who took the records and the reasons for their“food allergy”. Results: In a total of 1182 inpatients, 144 were reported as having foodallergies (15 out of 69 children). The causal foods in adults were fish (18.0%), fruits (14.4%) and shellfish (11.3%), while those in children were cowmilk and fruits (both 14.8%), and eggs, nuts, peanuts and soy (all 11.1%). The occupations of the reporting person were dietitians (57.6%), nurses(33.3%) and physicians (1.39%). The reason“food allergy”was determined was mostly from a self-report of symptoms (65.2%), followed by a posi-tive allergen-specific IgE antibody test (3.55%). 21.3% of the patients did not have any reason recorded. Conclusions: Food allergy was reported in12.2% of all inpatients, which is significantly higher than the estimated general prevalence in Japan (1-3%). In adults, fish was the leading cause ofavoidance in the study, which differs from the general population. Conversely, there was no significant difference in children. The reason for thesedifferences in prevalence may be that in adults, there was a tendency to avoid food depending solely on self-judgement, while in children, aller-gens were eliminated based on a doctor’s diagnosis. In addition, interviews about food allergy were made by people of various occupations, mostlyby non-specialists. Providing allergy-free meals requires careful confirmation in multiple steps until serving. Incorrect interviews can create“un-necessary food allergies”, that result in requiring huge time and effort, and may lead to human error. In order to obtain accurate information andprovide safe allergen-free meals, it is essential to use highly reproducible interview forms regardless of the interviewer.

203

PosterSession

PE20-7 The distribution of Mal d 1 protein, apple allergen component, in apples cultivated and consumed in Japan

Naoko Okishima, Chiyumi Suzuki, Takumi Fukuda, Shiho Nakayama, Masami Nitta (Department of Health and Nutritional Science, MatsumotoUniversity, Japan)

Background: Pollen-Food Allergy Syndrome (PFAS) is a type 2 food allergy in which main symptoms are localized in the oral cavity. There aremany patients with birch pollen allergy who concomitantly develop the apple PFAS at Hokkaido in Japan. Recently, the Betulaceae pollinosis pa-tients accompanied by the apple PFAS have been increasing in other regions of Japan. The amounts of allergens in some apple varieties is re-ported in Europe. However, the most cultivars are not common between Europe and Japan, and no information about the allergens of apples culti-vated in Japan are not available. In this regard, we first revealed and reported the mRNA expression levels of Mal d 1 in apples cultivated in Ja-pan, which is the major apple antigens. In this report, we estimate the amount of Mal d 1 protein in the apples cultivated and consumed in Japan.Methods: Fifteen varieties of apples, in which the Mal d 1 mRNA expression levels were lower than Fuji, were used. The Mal d 1 allergen was de-tected by the Western Blotting. Amount of the Mal d 1 specific bands were estimated by comparing with the band of 0.1 g of the recombinant Mald 1 protein as a standard. Results: Compared with Sun Fuji, the amounts of Mal d 1 protein were significantly less in most varieties like as Ourin,Korin, Sensyu, Shinano Red, Shinano piccolo and Toki. However, the amounts of Mal d 1 protein were more, even though the differences were notsignificant, than Fuji in apples of Sun tsugaru, Shinano Dolche and White sweet. Conclusion: In this report, we revealed that the expression levelsof the Mal d 1 mRNA partially correlated with the amount of the Mal d 1 protein in apples. However, the Mal d 1 protein should be estimated cor-rectly for the patients with the apple PFAS to avoid the allergy. Consequently, we are developing the sandwich ELISA to determine the quantita-tive value of the Mal d 1 proteins in apples precisely.

PE20-8 Determinants of parental burden among Hong Kong children with adverse food reactions

Ming Yan Rebecca Li, Agnes Sze Yin Leung, Gary Wong, Ting Fan Leung (Department of Paediatrics, The Chinese University of Hong Kong,Prince of Wales Hospital, Hong Kong)

Background: Quality of life (QoL) in families with food-allergic children is compromised due to lifestyle changes as a result of food avoidance. Thedegree of QoL impairment is geographically specific as food consumption patterns and social awareness towards food allergy varies considerablyacross the world. This study aimed to identify factors affecting QoL in parents with food-allergic children in Hong Kong and the interplay be-tween these factors and different aspects of living.Method: Clinical characteristics, patient history and response to FAQoL-PB questionnaire (Co-hen BL et al. J Allergy Clin Immunol 2004) of 110 participants were collected, and 92 of them were complete and analyzed in this study. TheFAQoL-PB questionnaire measures quality of life in parents with food-allergic children, specifically parental burden. The relationship betweenFAQoL-PB scores and different clinical and adverse food reaction (AFR) factors was analyzed by Mann-Whitney U test or student t test as appro-priate, and independent factors were identified by multivariate regression analyses. Results: Participants’ age was 0.7-20.2 years. Sixty-five (70.7%)patients reported adverse food reaction (AFR), 54 (58.7%) had physician-diagnosed food allergy and 54 (58.7%) with current food avoidance. Peanutwas the leading food causing AFR with 27 (41.5%) parent-reported AFR, followed by shellfish (n=23, 35.4%), egg and fish (n=18, 27.7%) and cow’smilk (n=14, 23.1%). Parental burden was found to be significantly greater in parents with children who had AFR towards more than three foods (p=0.040), with current food avoidance (p=0.003), and AFR caused by egg (p=0.027) and fish (p=0.036). Multivariate regression revealed number offood avoidance (β=0.421, p<0.001) was a significant predictor of parental burden. Factor analysis revealed that FAQoL-PB questionnaire meas-ured parental burden regarding social limitations and emotional distress. Conclusion: AFR to more than three foods, current food avoidance andAFRs toward egg, fish and cow’s milk are significantly associated with parental burden, social limitations and emotional distress. The number offood being avoided is a significant predictor for parental burden.

PE20-9 Case report of 9 childhood patients with buckwheat allergy

Xiaoyang Wang, Chuanhe Liu (Department of Allergy, Capital Institute of Pediatrics, China)

Background: To summary the clinical manifestation and analyze the laboratory change in children with buckwheat allergy, and to increase theawareness of the disease.Methods: Children suspected with buckwheat allergy were enrolled during July 2019 through January 2020 from outpa-tients in the hospital of Capital Institute of Pediatrics. The data of personal and family history, clinical symptoms, and previous exposure to buck-wheat were collected and necessary laboratory testing completed for all patients. Results: Nine children (6 boys, 3 girls) were enrolled, with theage at 6.4±3.6 years. The attack triggers were buckwheat taken in, using buckwheat pillow or buckwheat flour contact. Allergic symptoms ap-peared within 30 minutes in eight patients, and in 1.5 hours in one patient after exposure to buckwheat allergen. Children’s symptoms included cu-taneous (8/9, 88.9%), respiratory (7/9, 77.8%) and digestive (3/9, 33.3%) symptoms. Eight children ever had developed anaphylaxis. All nine chil-dren showed positive skin reaction to buckwheat flour, with degree of ++ or more, and one patient had positive reactions to kiwi fruit. The levelof total IgE in serum was from 155 kU/L to 443 kU/L, and grass pollen sensitized in 5 patients. The counting of eosinophil in peripheral blood was4% - 19.5%. All children had a history of using buckwheat husk pillows, and with bronchial asthma and/or allergic rhinitis ever diagnosed. Conclu-sion: Buckwheat allergy is common in young children, with varied clinical manifestations and high frequent anaphylaxis. Using buckwheat pillowmight be the way of buckwheat sensitization in children. Keywords: Buckwheat, allergy, children

204

PosterSession

PE20-10 Wheat allergy in children: 21 cases reports

Xiaoyang Wang, Chuanhe Liu, Mingjun Shao, Li Sha, Jing Zhao (Department of Allergy, Capital Institute of Pediatrics, China)

Background: To analyze and summarize the clinical features of wheat allergy in children to help increasing the awareness. Methods: Childrensuspected with wheat allergy in the outpatient of Capital Institute of Pediatrics from December 2018 to May 2019 were included. Clinical datawere collected, including the demographic profile, clinical symptoms, and some laboratory findings. Follow-up were conducted 3 months later bytelephone. Results: 21 children (15 boys, 6 girls) were finally enrolled. The median age was 21.5 months (range 10 to 54 months). All children hadallergic reactions within 2 hours after eating wheat food, and six of children also had reactions after contacting wheat flour. Children’s symptomsincluded cutaneous (20/21, 95.2%), respiratory (7/21, 33.3%), digestive (4/21, 19.0%) and cardiovascular (1/21, 4.8%) symptoms, and there were 11children that even had anaphylaxis. The total IgE level of serum allergy ranged from 86 to 5000 kU/L, a wheat IgE level of ten cases was morethan 100 kU/L, 4 cases were from 50 to 100 kU/L, 2 cases were from 17.5 to 50 kU/L, 3 cases were from 3.5 to 17.5 kU/L, and 2 cases were from 0.7to 3.5 kU/L. The serum allergen detection indicates that seven of patients were sensitive to egg white, four patients to milk, and one patient topeanut. Only five of children took the skin prick test, and all showed positive skin reactions to wheat flour. The peripheral eosinophil count in chil-dren was (0.47-1.00)×10^9/L. All children had a family history of allergy. Conclusion:Wheat allergy in children always appears early. The clinicalmanifestations are severe and various, mainly skin systems. Serum wheat IgE detection shows an important role in the diagnosis and evaluationof wheat allergy. Children with other food allergies and family history of allergies should be alert of the anaphylaxis and be treated seriously. Key-words: children; wheat allergy; clinical characteristic

PE20-11 An impaired bone mineral density in children with cow’s milk allergy

Komei Ito1), Tomomi Nakazato1), Shiro Sugiura1), Yoshihiro Takasato1), Teruaki Matsui1), Katsumasa Kitamura1), Harue Umemura2) (Aichi Children’sHealth and Medical Center, Japan1); Department of Nutrition, Nagoya University of Arts and Sciences, Japan2))

Background: Cow’s milk (CM) is the primary source of calcium intake. Persistent CM avoidance due to CM allergy (CMA) from infancy may re-sult in calcium deficiency, which might affect the bone mineral density (BMD) in children.Method:We recruited 46 children (30 boys) with CMA 7to 12 (median 9.5) years old. The BMD was measured via dual-energy X-ray absorptiometry (DEXA, Hologic) at the lumbar spine L1-L4. Gender-and age-related Z-scores were calculated based on the internal standard of the manufacturer. Results: At the time of DEXA testing, 28 childrenwere under complete elimination of CM products, and 18 were consuming <3 ml of CM as programmed oral immunotherapy. Complete or partialavoidance of hen’s egg (n=17 or 13) and wheat (n=2 or 9) was also performed. Eleven children (24%, 8 boys) had episodes of bone fracture. In the 7-to 9-year-old group, the average±standard deviation (SD) BMD (g/cm2) was 0.48±0.05 in the boys (n=17) and 0.52±0.02 in the girls (n=8). In the10- to 13-year old group, this value was 0.58±0.05 in the boys (n=13) and 0.63±0.10 in the girls (n=8, including 3 in early menarche). The Z-score ofthe all-age group was -1.69±0.73 in boys, which was significantly lower than that for girls (-1.1±0.95, p<0.01). Four boys (13%) showed a Z-score <-2.5, and 3 of them had 1, 2 and 3 episodes of bone fracture (n=1 each). Two boys, whose Z-scores were -3.3 and -2.3, also had fish allergy. In theboys, the prevalence of Z-score 2.0 was 58.3% in those who exercised for 2.0 h/week (n=12), which was significantly higher than in those who exer-cised for >2.0 h/week (5.6%, n=18, p<0.01). Conclusion: CMA influenced the BMD in children, especially boys. Concomitant fish allergy and littleexercise time further affected the BMD in children with CMA. We should provide special nutritional support to support calcium intake in childrenwith CMA.

PE20-12 Decreased bone mineral density of the school children with IgE-mediated cow’s milk allergy

Mika Ogata1), Nami Hirai1), Tomoyuki Mizukami1), Tetsuo Ikeda3), Soroku Nishiyama2) (Department of Pediatrics, National Hospital OrganizationKumamoto Medical Center, Japan1); Faculty of Human Life Science, Department of Nutritional Science, Shokei University, Japan2); Department ofPediatrics, Jikei Hospital, Japan3))

Background: Dairy products are one of the major sources of calcium (Ca). We investigated bone mineral density (BMD) of school children withIgE-mediated cow’s milk allergy (CMA) who had been removing dairy foods for a long time. And the efficacy of oral supplementation with Ca orCa and vitamin D (VD).Methods: Nineteen prepubertal children with persistent CMA were enrolled. Lumbar spine BMD (BMDL 2-4) was meas-ured by using dual-energy x-ray absorptiometry (DXA) and calculated z-scores based on the standard BMD of Japanese children by Nishiyama.Subsequently, the subjects were divided into the two groups, group 1 (Ca Lactate Hydrate 2 g/day) and group 2 (Ca 2 g/day and 1α-hydroxyvitamin D 0.25 g/day), compared the effects of taking the supplements. Results: Z-score was -2.4±1.3 (mean±SD), 74% of the subject hada score of -2 SD or less. Urinary Ca/Cr ratio, and 25-OH VD levels were low, although serum levels of Ca, phosphorus, ALP, and intact PTH werenormal. Of the 19 participants, 17 excluding 2 in group 2 received Ca and or VD supplementation. The observation period was 275 days (240-360days), and the mean compliance rate was 5.0 days per week. At the end of treatment, Z-score was -2.1±1.4, which was not improved, and therewas no difference between the two groups. Conclusion: These CMA children had low BMDL 2-4. Considering their insufficient Ca intake as onereason, the BMD of healthy children without CMA may be low because many Japanese does not take enough Ca. This trial was safe, but the im-provement in BMDL 2-4 was poor. The possible reasons were low adherence, low supplement dose, and short treatment period. More aggressiveintervention in CMA patients is needed.

205

PosterSession

PE20-13 The summary of oral food challenge tests for the past two years at a secondary care hospital in Japan

Mikita Yamamoto, Kenji Waki, Yoshio Aragaki (Department of Pediatrics, Kurashiki Central Hospital, Japan)

Background: The result of oral food challenge (OFC) tests varies according to its design and patients’ background. Objective: The purpose of thisstudy was to evaluate the safety and efficacy of OFCs at our hospital. Subjects: We retrospectively analyzed 166 patients who had undergone atotal of 426 OFCs from June 2017 to May 2019 at Kurashiki Central Hospital. Methods: Open OFCs were performed. We judged OFCs positivewhen patients had obvious objective symptoms. When symptoms were ambivalent or subjective, we advised them to take the same amount athome. Final judgment was made by checking for reproducible symptoms at the next visit. Results: The average number of OFCs per patientswas 2.6 (range, 1-9) times. 100 patients were male, 66 were female. Median age was 3.9 (range, 0.4-17.9) years old. History of immediate reaction wasseen in 286/426 (67.1%) of the patients. OFCs were positive in 78/426 (18.3%). When all 426 OFCs were classified by allergen, hen’s egg, cow’s milk,and wheat were the most common. The positivity rate classified by challenged dose were as follows: 1/32, 1/8, 1/2 of whole hen’s egg were 12/78(15.4%), 13/79 (16.5%), 5/30(16.7%), 3ml, 25ml, 50ml of cow’s milk were 12/45 (26.7%), 5/33 (15.1%), 4/18 (22.2%), and 2g, 15g, 50g of Udon noodlemade of wheat were 6/26 (23.1%), 9/19 (47.4%), 2/10 (20.0%). Anaphylaxis was experienced in 24/426 (5.6%). Treatment for symptoms were neededin 70/426 (16.4%). Medication used for treatment were anti-histamine 62/426 (14.6%), steroid 32/426 (7.5%), β2-agonist inhalation 34/426 (8.0%), andadrenaline 1/426 (0.2%). 91.0% of the patients succeeded in partial removal of their dietary restriction at an average of 2.1 (range, 0-7) times. Con-clusions:Most of the patients were able to partially remove their dietary restriction. Safety of OFCs were acceptable in our hospital.

PE20-14 Safety of low-dose cow’s milk oral food challenges administered in two doses at 60-minute intervals

Nana Kojima1), Makoto Nishino1), Naoto Otake1), Toshinori Kitatsu1), Noriyuki Yanagida1), Sakura Sato2), Motohiro Ebisawa2) (Depertment of Pediat-rics, National Hospital Organization Sagamihara National Hospital, Japan1); Department of Allergy, Clinical Research Center for Allergology andRheumatology, National Hospital Organization Sagamihara National Hospital, Japan2))

Background: According to the Japanese guidelines for food allergy 2017, the dose interval for an oral food challenge (OFC) is recommended to beat least 20 min. However, the optimal interval between doses remains unknown. This study aims to assess the safety of low-dose heated cow’smilk OFCs administered in two doses with a 60-minute interval (two-dose OFC). Methods: We retrospectively analyzed two-dose OFCs per-formed with low-dose (3 mL) heated cow’s milk from April 2014 to April 2019. These were carried out with an initial dose (1/4 of total challengedose) and followed by a second dose (3/4 of total challenge dose) after 60 min if no symptoms were observed. Results: There were 430 patients in-cluded in the two-dose OFCs, and 210 of them showed positive results (positivity rate: 49%). The median age of patients with positive results was3.9 years. Among them, 169 (80%) had a history of immediate reaction to cow’s milk. The median specific IgE values of milk and casein were 36.8and 35.0 kUA/L, respectively. Eighty-eight (42%) cases were positive after the initial dose and 122 (58%) cases after the second dose. The mediantime OFCs were determined to be positive was 40 min after the initial dose, and 36 min after the second dose. Severe symptoms were recognizedin 5 (6%) cases after the initial dose and in 2 cases (2%) after the second dose. Anaphylaxis was observed in 33 (38%) cases after the initial dose andin 47 (39%) cases after the second dose. Conclusion: The 60-min interval in two-dose OFCs of 3 ml heated cow’s milk enabled many patients toavoid additional intake since OFCs were deemed positive after a median of 40 min. Although anaphylaxis was observed in 38% of positive cases,the risk was equally distributed between the initial and second dose, which suggests that two-dose OFCs were relatively safely performed.

PE20-15 Clinical features of Chinese yam allergy in Japanese children

Hiroaki Obayashi1,2), Katsumasa Kitamura2), Teruaki Matsui2), Yoshihiro Takasato2), Shiro Sugiura2), Komei Ito2) (Department of Pediatrics, MatsudoCity General Hospital Children’s Medical Centre, Japan1); Department of Allergy, Aichi Children’s Health and Medical Center, Japan2))

Background: Chinese yam (Dioscorea polystachya ) is widely consumed in East Asia, but there are few reports of allergic reactions. It is not clearhow much allergic reactions occur in yam-sensitized patients, and whether heating changes the antigenicity.Methods: Paired open oral food chal-lenges (OFCs) using raw and cooked yam were performed for yam-sensitized children from August 2018 to February 2020. Yam was heated inthe microwave for 3 minutes at 500W for cooked yam, and each OFCs was typically conducted with 5-10-20-50 g at 40 minutes intervals. The se-verity of provoked symptoms was calculated by the Total Score (TS) of Anaphylaxis Scoring Aichi (ASCA) and TS divided by the cumulative pro-tein dose (TS/Pro). Results: Ten patients underwent both raw and cooked yam OFCs. The median (range) age was 6.5 (3-15) years, and 2 weremales. The median total IgE titer was 1342 (136-1931) IU/mL, and yam specific IgE was 11.1 (1.3-103) UA/mL. Raw yam OFCs showed positive re-sults in 7 patients (70%) with the median 41 (7-85) g of cumulative dose and TS/Pro of 9.7 (5.3-71.4). Six of them (86%) had negative results forcooked yam OFCs. Cooked yam OFCs provoked allergic reactions in only 1 patient with 85 g of cumulative dose and TS/Pro of 5.3. This patienthad positive raw yam OFC with 35 g of cumulative dose and TS/Pro of 26.0. Gastrointestinal symptoms were provoked in all patients with posi-tive results for each OFCs. No patient required intramuscular adrenaline injections. Conclusion: Most of the yam-sensitized children reacted toraw yam, but tolerated cooked yam. The results of this study suggest that the antigenicity of yam changed by heating.

206

PosterSession

Poster Session 21Food allergy-Immunotherapy

PE21-1 Three-year outcomes of oral immunotherapy using dried egg powder for severe hen’s egg allergy

Koki Sasamoto1), Ken-ichi Nagakura1), Noriyuki Yanagida1), Sakura Sato2), Motohiro Ebisawa2) (Department of Pediatrics, National Hospital Organi-zation Sagamihara National Hospital, Japan1); Department of Allergy, Clinical Research Center for Allergy and Rheumatology, National HospitalOrganization Sagamihara National Hospital, Japan2))

Background: Children with hen’s egg allergy who have a history of anaphylactic reactions or high egg white specific IgE (sIgE) levels exhibit dif-ficulties in acquiring tolerance. Few studies of long-term oral immunotherapy (OIT) for severe egg allergy have been conducted. We investigatedOIT using dried egg powder for 3 years in children with severe egg allergy.Method:We included children 5 years or older and confirmed the ob-jective reactions in oral food challenge (OFC) of 250 mg egg protein. Of 92 children, 22 underwent OIT between 2015 and 2016 (OIT group), and 25children who did not receive OIT underwent repeated OFC as historical control group. In OIT group, each home initial dose was determined dur-ing 5 days of hospitalization. They gradually increased the amount of dried egg powder to 1000 mg egg protein (target dose) and continued OITfor more than 1 year. When no symptoms were observed for 3 months, they underwent an OFC of 3100 mg egg protein (half egg) on consecutivedays after cessation of OIT for 2 weeks. The children who passed the OFC was classified as achieving“short-term unresponsiveness”(STU). Wecompared the outcomes for 3 years between OIT and historical control groups. Results: At baseline in OIT and control groups, a history of ana-phylaxis to hen’s egg was observed in 64% and 41% of children, the median egg white-/ovomucoid-sIgE levels were 35 and 23 kUA/L/28 and 19kUA/L, respectively. The rates of achieving STU 3 years later were 54% and 8%, respectively (p<0.001). The reduction rates of egg white-/ovomucoid-sIgE from baseline to 3 years later were 64% and 42% (p=0.036)/74% and 33% (p<0.001), respectively. During OIT, children experi-enced adverse reactions at rates of 73% per ingestion in hospital and 14% per ingestion at home. One child developed anaphylaxis requiring intra-muscular adrenaline at home. Conclusion: OIT using dried egg powder induces immunological changes and has the capability of achieving STUin half of children with severe hen’s egg allergy within 3 years.

PE21-2 Safety of ultralow-dose of antigen oral immunotherapy in pediatric patients with severe peanut allergy: induction, fixed-dose, andescalation phases

Kyoko S Nishikage1,2), Takeharu Yamanaka2) (Yokohama Nishikage Clinic: Kids and Allergies, Japan1); Department of Biostatistics, School of Medi-cine, Yokohama City University, Japan2))

Background: For pediatric patients’ anaphylactic peanut allergy, oral immunotherapies have not been tolerable due to adverse events during thecourse. We examined the induction of ultralow-dose immunotherapy and report on its safety. Methods:We firstly made 5-fold dilutions of peanutallergen extract which contained 127 g of peanut protein per ml (ALK Abello, Denmark). Second, the thresholds of skin prick tests (SPT) of pa-tients were examined by using the above mentioned dilutions. The induction phase began with swallowing 0.1 ml of the threshold dose of SPT.The starting dose was adjusted to a weaker one if there were any adverse reactions. The confirmed doses were kept as the medication doses 2times a day for a month. Third, each medication dose was increased to 1.5 times stronger every month if the oral challenge showed no reactions.Results: Between May and Dec 2019, the ultralow-dose of antigen oral immunotherapy was administered to 6 patients from the single medicalcenter; median age, 7 (range: 3-15); 3 males. A history of anaphylaxis, severe skin reaction, and a high level of Ara h2 without an accidental inges-tion of peanut was observed in 4, 1, and 1 out of 6, respectively. At baseline, the median peanut-IgE level was 22.5 (range: 1.45-100) UA/ml, the me-dian Ara h2 level was 17.8 (range: 1.21-25.5), and the thresholds of SPT varied from 1/55 to 1/57 of the original extract. The rates of adverse reac-tions per ingestion during the induction, the fixed-dose, and the escalation phase thereafter, were 57% (8/14), 0% (0/1020), and 2.9% (1/34), respec-tively. The reactions in the induction and escalation phases were mild, none of which required intramuscular adrenaline. The method has been tol-erable since there was no adverse reaction in the fixed-dose phase at home. All the patients could raise their thresholds up to 125 to 200 timesstronger in 1 year. Conclusions: Ultra low-dose antigen oral immunotherapy safely increased the threshold of each patient. Efficacy results will bereported in a long-term follow-up study.

PE21-3 Comparison of the efficacies of low-dose and high-dose slow oral immunotherapy for egg allergy

Yuri Takaoka, Junko Kumon, Tomohiro Yamaguchi, Rumi Ueno, Yuki Tsurinaga, Tamana Nakano, Yohei Fukasawa, Amane Shigekawa,Yukinori Yoshida, Makoto Kameda (Department of Pediatrics, Osaka Habikino Medical Center, Japan)

Background: Oral immunotherapy (OIT) for egg allergy has been reported as an effective modality to raise the threshold level. However, the riskof severe symptoms after this treatment has been documented previously; therefore, a reliable method to reduce this risk is required. Objective:We aimed to compare the efficacy and safety of low-dose and high-dose OIT allergy treatments using boiled egg white (EW). Method: Patientsaged 3 to 15 years with a moderate allergy to hen eggs were included in this study. According to the maximum maintenance EW dose adminis-tered, the patients were randomized into two groups: low-dose OIT group (2 g) and high-dose OIT group (20 g). The starting dose of OIT was de-termined as per the result of an oral EW challenge test. Following this, the doses were increased to the target maintenance in-home dose. Anotheroral EW challenge test was performed after 6 months of OIT. The primary endpoint was the final dose determined from the EW challenge test af-ter OIT. Adverse events during OIT were evaluated from the patients’ diaries. Results: Fifty-one patients (low-dose group: n=23; high-dose group:n=28) were enrolled. The median final dose of the EW challenge test before OIT was 2 g. OIT was completed in 15 low-dose patients and 16 high-dose patients for 6 months. The median final dose of the EW challenge test after 6 months of OIT was 10 g in both groups (p=0.800, Mann-Whitney U test). No patients used epinephrine during OIT. Conclusions: The effect and the risk of severe symptoms were not different betweenlow-dose and high-dose OIT for moderate allergy to eggs. Therefore, low-dose OIT is an appropriate treatment modality for the first 6 months ofthe patient developing an allergy. Our findings highlight the efficacy of both treatment dosages administered over a long period and attempt toportray an effective risk-reduction method against the adverse effects of OIT.

207

PosterSession

PE21-4 Low achievement of sustained unresponsiveness in oral immunotherapy for persistent cow’s milk allergy

Toshinori Nakamura, Kosei Yamashita, Yuki Okada, Mayu Maeda, Taro Kamiya, Takanori Imai (Department of Pediatrics, Showa UniversitySchool of Medicine, Japan)

Background: Oral immunotherapy (OIT) may have a more difficult increasing dose in cow’s milk allergy (CMA) patients, often requiring an ex-tended therapeutic period. We should clarify the prognosis of CM OIT, helping the patients to decide either staying in the therapy or not. Hence,we aim to investigate the rates of sustained unresponsiveness and the period to attain the outcome in CM OIT. Methods: This retrospectivestudy includes CMA patients who have undergone the OIT in the last eight years in our hospital. The patients’ characteristics and outcome werereviewed from medical records. Sustained unresponsiveness (SU) was defined as the negative response to the oral food challenge with 200 mLwith at least two weeks of the complete elimination. The end of the therapy for patients dropped-out was defined as the final day of either OITtherapy or the clinic presence. Survival analysis was applied. Numerical values show median (IQR) for descriptive analysis and mean (95% confi-dent interval) for outcomes. Results: Ninety-six patients were starting OIT at 6.8 (5.7-9.0) year-old. The observational period was 2.0 (1.1-2.7) years.The level of IgE specific CM was 21.5 (9.1 51.9) UA/mL. OIT starting dose was 0.5 (0.2-5) mL. 34 (35.4%) of the subjects attained SU. The SU attainrate was 0.16 (0.12-0.23)/person-year. Estimated probability of SU increased to 0.56 (0.42-0.70) by 3 years after OIT start, then stayed flat after-wards. Hazard ratios for risk factors in univariate analysis were: starting age [1.14 (1.02-1.28), p=0.02], starting dose [1.02 (1.01-1.03), p<0.001], andthe level of IgE specific CM [0.80 (0.60-1.05), p=0.11]. In multivariate analysis, Only starting dose associated significantly with increasing the SU at-tain rate [1.02 (1.00-1.03), p=0.005]. Conclusions: This study clarifies that of CMA patients, approximately a half can attain SU over 3 years of OIT.However, those who failed to achieve SU in this period may hardly achieve in the following therapy. These findings may well support patients’ de-cision making for when to end the therapy.

PE21-5 Food allergy and oral immunotherapy affect food preferences

Kenji Toyokuni, Kiwako Yamamoto-Hanada, Yoshitsune Miyagi, Hiroya Ogita, Tomoyuki Kiguchi, Yusuke Inuzuka, Koji Nishimura,Fumi Ishikawa, Makoto Irahara, Miori Sato, Mayako Saito-Abe, Yumiko Miyaji, Shigenori Kabashima, Tatsuki Fukuie, Yukihiro Ohya (AllergyCenter, National Center for Child Health and Development, Japan)

Background: Children with food allergies can feel anxious and fearful about the consumption of culprit foods. However, there is limited evidenceavailable on how food allergies can affect patients’ food preferences. The aim of this study was to examine the association between food allergies,oral immunotherapy (OIT), and food preferences.Methods:We performed a cross-sectional study at our center’s outpatient department from No-vember 2019 to December 2019. Participants answered questions on their history of allergic reactions, current consumption conditions, and pref-erences for each food. The preference score for each food was based on a 5-point scale (1=dislike, 5=like). We analyzed whether food allergies andOIT affected their preference scores, using the Wilcoxon signed-rank test. Results: There were 476 participants enrolled in this study, and weanalyzed their answers about preferences on egg (n=290), milk (n=255), and wheat (n=248). The prevalence of past allergic reactions to each foodwas 63% (egg), 40% (milk), and 35% (wheat); and 46% (egg), 27%(milk), and 21% (wheat) were undergoing OIT treatment. The preference score(mean±standard deviation) for each was 3.2±1.4 (egg), 3.5±1.4 (milk), and 4.2±1.0 (wheat), respectively. Participants with a history of allergic re-action to each food had a lower preference score than those without any past allergic reaction history (egg: 2.9 vs 3.7; P<.0001, milk: 2.8 vs 4.0; P<.0001, wheat: 3.9 vs 4.4; P<.0001). Participants on current OIT had lower preference scores than those not on OIT (egg: 2.9 vs 3.4; P=.0043, milk:2.6 vs 3.8; P<.0001, wheat: 3.5 vs 4.4; P<.0001). Conclusion: Food allergies and OIT treatment can cause patients to dislike certain foods. We shouldconsider the patients’ food preferences in food allergy management.

PE21-6 Long-term quality of life of persistent food allergy patients in post oral immunotherapy

Kosei Yamashita, Toshinori Nakamura, Toshiyuki Takagi, Yuki Okada, Mayu Maeda, Taro Kamiya, Takanori Imai, Katsumi Mizuno (Departmentof Pediatrics, Showa University School of Medicine, Japan)

Background: Oral immunotherapy (OIT) can desensitize many persistent food allergy patients. However, little is known about how the therapyimpacts on the quality of life (QOL) of the patients in the long-term period. To characterize in QOL change, we investigated post immunotherapypatients regarding satisfaction for the treatment, the degree of anxiety about allergy reactions, improvements of daily life, dietary restrictions ontheir children’s group life, and concerns on eating out. Methods: The subjects are patients who underwent OIT in our hospital, attaining the de-sensitization to following causative foods in the last five years: Hen’s egg, Cow’s Milk, Wheat, or Tree Nuts. We modified the QOL questionnairefor food allergy patients and sent to the guardians via post. Numerical values show mean and standard deviation. Results: Of 145 subjects, 94(64.8%) provided the valid response. The period from the end of OIT was 23.6 (7.2-40) months. 88 (93.6%) parents were highly satisfied with theirlife after OIT. 91 (96.8%) felt improvement in their daily life, and 89 (94.7%) reported reduced anxiety about allergy reactions. 93 (98.9%) had no con-cerns in eating out, and 47 (50.0%) had no dietary restrictions on their children’s group life. 54 reported allergic reactions provoked in post OIT pe-riod, yet 50 (92.6%) were highly satisfied with the therapy. Conclusion: The survey shows that OIT can significantly improve patients’ QOL for along time after the treatment ends. Surprisingly, this effect was also observed in most parents whose children had failed sustained unresponsive.

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PosterSession

PE21-7 Effectiveness and safety of rush and slow oral immunotherapy in our facility

Tomonori Kadowaki, Yukiko Otsuka, Yuki Okada, Kanako Maruta, Kumiko Miyazaki, Yuko Shimokawa, Koji Tatebayashi, Michinori Funato,Hideo Kaneko (Department of Pediatrics, National Hospital Organization Nagara Medical Center, Japan)

Background: Oral immunotherapy (OIT) is a treatment in which patients consume gradually increasing quantities of the food leaded to allergicreaction in order to induce desensitization followed by sustained unresponsiveness. However, rapid OIT (ROIT) which is the method that intakeof the allergen increases to the amount to induce desensitization in a few weeks often occurs the severe side effect such as anaphylaxis. In our fa-cility, if patients develop frequent severe allergic symptoms during the desensitization induction period in hospitalization, their treatments arechanged ROIT to slow OIT (SOIT) which is the method that the increase of allergen during hospitalization is set small amount followed by gradu-ally increasing on an outpatient basis. In this study, we evaluated the effectiveness of this protocol.Methods: Using the cases performed ROIT orSOIT with egg, milk, and wheat between April 2012 and December 2017 in our hospital, we performed retrospective study to examine theirchanges of intake and specific IgE levels over two years. The side effect during course was also evaluated. Results: The numbers performed OITwith egg, milk, and wheat were 28, 15, and 8, respectively. The patients switched to SOIT for egg, milk, or wheat were 5, 10 and 5, respectively. Inaddition, the number of patients whose OIT with egg, milk, or wheat were stopped were 2, 2, and 1, respectively. Over the course of 2 years, thespecific IgE values of egg white, egg yolk, ovomucoid, milk, and casein were significantly decrease (the p values of each were 0.0002, 0.0164, <0.0001, 0.0178, and 0.0010, respectively). On the other hand, more than half of the cases who transitioned to SOIT developed frequent allergicsymptoms more than 10 times a year. Conclusion: Even in the cases of transition to SOIT, it is necessary to give sufficient explanation to the pa-tients before starting treatment because side effects may occur.

PE21-8 Factors associated with the safety of initials dose of slow low-dose oral immunotherapy

Shiro Sugiura, Katsumasa Kitamura, Teruaki Matsui, Yoshihiro Takasato, Komei Ito (Department of Allergy, Aichi Children’s Health and MedicalCenter, Japan)

Background:We have already reported the feasibility, efficacy and safety of slow low-dose oral immunotherapy (SLOIT) which applied severity-stratified initial/maintenance dose (Allergology International). The initial dose of SLOIT was determined as 1/5 1/100 of the symptom-provokingfinal dose stratified by the severity of the provoked symptoms (total score of ASCA: TS) in the low-dose oral food challenges (OFCs, final dose ≦ 5g of boiled egg white, whole milk, or udon noodle). We instructed participants to continue the initial dose everyday for at least one month. The aimof this study was to identify factors associated with the safety of the initial dose. Methods: The background characteristics of participants werecompared among 3 groups: participants with no symptom during the first month, with symptom(s), and withdrawal due to allergic symptoms. Re-sults: Between April 2015 and March 2019, total 451 children were enrolled in SLOIT study for hen’s egg (n=225), cow’s milk (n=121), and wheat (n=105). Twenty-one children (4.7%) withdrew from SLOIT (14 children [3.1%] due to allergic symptom) in early phase of SLOIT, however, no par-ticipants developed anaphylaxis. Among remaining 430 children, 199 allergic symptoms were provoked in total 11379 ingestion (1.7% per inges-tion) of 113 children (symptom group), whereas 317 children (73.7%) did not experienced any symptoms during the first month (no symptomgroup). Although age, sex, antigen, atopic dermatitis, the protocol of the entry-OFCs, TS and threshold dose in the entry-OFCs were not signifi-cantly different among 3 groups, the proportion of children with bronchial asthma was higher in worse outcome: 30.0%, 38.9%, 64.3% of no symp-tom, symptom(s), withdrawal group respectively (p=0.012). TS/threshold dose was higher in withdrawal group compared with no symptom group(p=0.038). Conclusion: Severity-stratified initial dose of SLOIT based on the threshold dose and severity of symptoms in the OFCs showed highsafety for the participants with various background. Careful observation/treatment of bronchial asthma and further stratification of initial dosefor children with high TS/threshold dose may be useful for safer therapy.

PE21-9 Examination of the long-term effect of oral immunotherapy in children with cow’s milk allergy

Ryohei Suzuki, Yuriko Sekiguchi, Nagatoshi Sagara, Akiko Aota, Kenichi Akashi, Toshio Katsunuma (Department of Pediatrics, Daisan Hospital,The Jikei University School of Medicine, Japan)

Background: Previously, we conducted a 48week intervention trial (a randomized controlled trial) on the effect of oral immunotherapy (OIT) inchildren with severe cow’s milk (CM) allergy (ORIMA study; UMIN000005784). The results of the ORIMA study showed, the rate of a negativeCM challenge test at study completion was significantly higher in the treatment group in comparison with control group. However, the annualepisode of anaphylactic symptoms was about 1.0 per patient. In this study, we examined the long-term treatment effect in children whom wewere able to follow-up for at least two years after the completion of the 48 week-intervention. Objective: To confirm the long-term effect of OITfor CM. Methods: After the ORIMA study, the subjects who wished to continue the therapy in the long-term continued to ingest CM daily. Theupper limit of the intake dose was 100mL of CM. The primary endpoint was the changes in the CM-specific IgE and casein-specific IgE levelsthree years after the start of OIT. As secondary endpoints, we estimated the amount of CM intake and changes in the threshold three years afterthe start of OIT. Results: Eight children were examined in this study, and the median age at the start of OIT was 5.6 years (3.1-8.0). At the start ofOIT, CM-specific IgE was 52.6±42.4 UA/mL (mean±SD), casein-specific IgE was 54.0±43.5 UA/mL, and the threshold dose to induce symptomswas 7.6±13.2 mL. Three years after the start of OIT, CM-specific IgE was 9.2±15.0 UA/mL, casein-specific IgE was 9.1±15.4 UA/mL, and theamount of CM that the subjects could tolerate was 128.7±63.5 mL (4504.1±3520.8%). The rates of changes in CM-specific IgE, casein-specific IgE,and the amount of CM that the subjects could tolerate were all statistically significant. Conclusion: Results of this study demonstrated the long-term effectiveness of CM OIT, because it is very difficult to acquire true immunological tolerance in one year.

209

PosterSession

PE21-10 Exercise-induced allergic reactions after achievement of desensitization to cow’s milk and wheat

Shohei Kubota, Katsumasa Kitamura, Teruaki Matsui, Yasuhiro Takasato, Shiro Sugiura, Komei Ito (Department of Allergy, Aichi Children’sHealth and Medical Center, Japan)

Background:We have recently reported that the majority of patients who are successfully desensitized with rush oral immunotherapy (OIT) forwheat induce exercise-induced allergic reaction on desensitization (EIARD). There are also reports of experiencing EIARD after achieving desen-sitization with slow OIT in patients with CM and wheat allergies. We analyzed the result of exercise provocation tests (EPTs) for the diagnosis ofEIARD in patients who achieved desensitization with slow OIT for CM and wheat allergies. Method: This is a retrospective chart review of 74EPTs (CM, n=43; wheat, n=31) performed in Aichi Children’s Health and Medical Center from March 2012 to December 2019. The EPTs wereperformed for the patients who were desensitized to at least 6600 mg CM protein or 5200 mg wheat protein with slow OIT and were judged to behigh-risk of EIARD, e.g. patients who have history of allergic symptom after unintended exercise during OITs. In EPT, the patients ingested theirmaximum desensitized dose, and underwent either free running, treadmill or stepping exercise. We determined EIARD positive if the EPTs werepositive or the definitive episodes were seen after negative EPT. The clinical characteristics of the patients and provoked symptoms by EPTwere analyzed. Results: The EIARD-positive was 49% (21/43) for CM and 48% (15/31) for wheat. The median age at EPT for CM and wheat was10.5 and 9.4 years old, respectively. Among the EIARD-positive patients, skin symptoms were observed in 76% (16/21) and 87% (13/15), and respi-ratory symptoms were observed in 57% (12/21) and 53% (8/15) for CM and wheat challenge, respectively. Two children (5%) were treated withadrenaline injection in CM EPT. Among the EIARD-positive patients, 13 patients (CM, n=6; wheat, n=7) underwent second EPT, and EIARD dis-appeared in 8 (CM, n=4; wheat, n=4). Conclusion: EIARDs are observed not only after rush OIT but also in slow OIT for CM and wheat.

PE21-11 Factors related to treatment outcome and adverse events in peanut rush oral immunotherapy

Tomonori Ishiguro, Katsumasa Kitamura, Yoshihiro Takasato, Teruaki Matsui, Shiro Sugiura, Komei Ito (Department of Allergy, Aichi Children’sHealth and Medical Center, Japan)

Background: Rush oral immunotherapy (ROIT) has been reported as an effective treatment in achieving desensitization. We aimed to identifyfactors related to the outcome and adverse events in the rush phase of peanut ROIT.Methods:We retrospectively reviewed the medical charts of21 patients who underwent peanut ROIT in our department from April 2014 to March 2020. ROIT was performed in patients over 5 years of agewith threshold dose of less than 2 g peanut butter (equivalent to 500 mg peanut protein). After a positive oral food challenge (OFC), rush phase ofROIT was carried out in hospital with an initial dose determined by the threshold dose and symptom severity during OFC. During the rushphase, increasing doses of peanut butter were given 2 to 4 times a day for 12 days, aiming to reach the target dose of 3 g peanut butter. We exam-ined whether the background characteristics and the severity of provoked symptoms in the OFC (total score of Anaphylaxis Scoring Aichi: TS)(1) divided by the cumulative protein intake (TS/pro) were related to the outcome and adverse events during the rush phase of ROIT. Results: Ofthe 21 patients, 13 patients achieved the target dose. Comparing the achieving vs. non-achieving groups, the median (range) age was 12.1 (9.5-19.3)vs. 9.7 (7.1-14.3) years. The median peanut- and Ara h 2-specific IgE (sIgE) levels (UA/mL) were 28.8 (5.15-345) vs. 66.5 (1.79-332), and 25.4 (4.57-192)vs. 35.8 (0.99-171), respectively, with no statistical differences. The median TS/pro showed significant difference between the groups with 77 (1.1-532) vs. 545 (98-984) (p=0.007). TS/pro showed significant inverse co-relation to the achieved dose (r=-0.716, p<0.001). TS/pro also co-related to thenumber of moderate adverse events (TS10) (r=0.711, p<0.001). Age, gender, complication of other allergic diseases and other food allergies werenot significantly related to the outcome and adverse events. Conclusion: TS/pro was the only predicting factor related to the outcome and ad-verse events in the rush phase of peanut ROIT.

PE21-12 Exercise-induced allergic reactions on desensitization to cow’s milk after rush oral immunotherapy

Genki Tsuji, Teruaki Matsui, Yoshihiro Takasato, Katsumasa Kitamura, Shiro Sugiura, Komei Ito (Department of Allergy, Aichi Children’s Healthand Medical Center, Japan)

Background:We have previously reported the frequency of exercise-induced allergic reactions on desensitization (EIARDs) after successful rushoral immunotherapy (ROIT) for wheat allergy (Furuta T, Allergy 2020, doi: 10.1111/all.14182). In that report, 66.7% of the subjects were diagnosedas EIARD+, which remained 5 years in 52.4% of the patients. In this study, we have examined the frequency of EIARDs and the associated riskfactors in ROIT for cow’s milk allergy (CMA). Methods: We retrospectively performed a chart review of the patients in January 2020 who re-ceived the ROIT for CMA. ROIT protocol consisted of rush phase for 12 days in hospital, followed by slow-increase and maintenance phase athome. During 2010-2014, 43 patients underwent a ROIT for CMA, and 34 patients achieved a full-dose intake of CM (6.6 g of CM protein). Exercise-provocation tests after taking full-dose CM (Ex-P) were performed in 32 patients to diagnose EIARD. In some patients, Ex-Ps were repeated to ex-amine the resolution, or when the patient had a suspicious event of EIARD even after passing the 1st Ex-p. Time-course of the specific IgE (sIgE)levels to CM extract, casein, α-lactalbumin and β-lactoglobulin was analyzed using ImmunoCAP. Results: At lease 1 episode of EIARDs wereobserved in 17 patients (50.0%), which remained 5 years in 11 patients (32.3%). Of the EIARD+ patients, 12 patients failed in the 1st Ex-P. Even inthe patients who passed the 1st Ex-p, 2 patients failed in the 2nd Ex-P, and 1 patient had a convincing EIARD event. There were no differences inthe clinical backgrounds, severity of CMA before ROIT and the sIgE levels between the EIARD+ and EIARD－ patients. The sIgE levels to eachcomponent decreased almost equally after 1 and 2 years of ROIT, irrespective of the EIARD+ or EIARD-. Conclusions: As with OIT for wheat al-lergy, EIARDs were frequently observed and remained for a long period after successful ROIT for CMA. It was difficult to predict EIARD by sI-gEs or clinical backgrounds.

210

PosterSession

PE21-13 ω-5 gliadin-sIgE/total IgE predicts long-term outcome of low-dose OIT for severe wheat allergy

Ken-ichi Nagakura1), Noriyuki Yanagida1), Sakura Sato2), Yoko Miura1), Makoto Nishino1), Kyohei Takahashi1), Tomoyuki Asaumi1),Kiyotake Ogura1), Motohiro Ebisawa2) (Department of Pediatrics, National Hospital Organization Sagamihara National Hospital, Japan1); Depart-ment of Allergy, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan2))

Background: Little is known about the long-term follow-up of wheat oral immunotherapy (OIT). We analyzed the outcome and predictive factorsof low-dose OIT for patients with severe wheat allergy over 3 years.Methods: Eligible subjects were aged 5 years older who developed objectivesymptoms during an oral food challenge (OFC) of 53 mg wheat protein. After admission for 35-day build-up phase, patients gradually increasedwheat ingestion to 53 mg/day (target dose) and then continued 53 mg ingestion at home. One year later, patients who could ingest 53 mg withoutsymptoms for 3 months underwent 400660mg OFC to confirm short-term unresponsiveness (STU) after 2 weeks of avoidance. Reactive patientscontinued taking 53 mg, and repeated 400660 mg OFC one year later. We compared the baseline profiles between the STU group in which the pa-tients passed an OFC with 400 mg or more within 3 years and non-STU group in which patients did not achieve STU within 3 years. Results:Twenty-seven patients received low-dose wheat OIT. The median age was 6.7 years and 96% of patients had a history of wheat anaphylaxis. Themean threshold to induce symptoms was 33.4 mg. The median wheat-, gluten, and ω-5 gliadin--sIgE levels were 248 kUA/L, 315 kUA/L, and 12.7kUA/L, respectively. The proportions of STU were 7%, 26%, and 33% after 1, 2, and 3 years, respectively. After 3 years, measurements for theSTU group vs non-STU group showed the following results: baseline ω-5 gliadin-sIgE level, 4.1 vs 28.2 kUA/L (p=0.01); wheat-sIgE/total IgE ra-tio, 16.4% vs 25.5% (p=0.09); ω-5 gliadin-sIgE/total IgE ratio, 0.7% vs 1.8% (p=0.001). While ROC curve predicted STU achievement 3 years later,the AUC of the ω-5 gliadin-sIgE/total IgE ratio was at its highest (.877), and cut-off level was 1.05% (sensitivity, 78%; specific, 100%). Conclusions:Continuing low-dose OIT in patients with severe wheat allergy increased the rate of STU yearly. The baseline ratio of ω-5 gliadin-sIgE/total IgEwould be a good predictor for STU achievement 3 years later.

PE21-16 Does oral immunotherapy for food allergy impact allergic chidren BMI?

Skander Larakeb1), Carine Billard1), Patricia Tome2) (Department of Pediatrics, Meaux General Hospital, France1); Allergology Unit, Aulnay SousBois Hospital, France2))

Introduction: Children with food allergies frequently have eating disorders and a poorly diversified diet, responsible for lower anthropometric pa-rameters than those of non-allergic children. OIT is frequently performed with commercial products. For the most frequent allergens, these prod-ucts are reputed to be unhealthy, rich in sugar and fat, which can create reluctance on the part of parents. The objective of this study is to deter-mine the evolution of the body mass index (BMI) in children with food allergies during oral immunotherapy.Method: A retrospective descriptivestudy of a population of 75 children followed in an allergology consultation at the Meaux hospital for oral immunotherapy between January 2013and December 2019. Results: There was a significant increase in the mean cohort BMI on OIT (16.7 before OIT, vs 17.9 on OIT, p<0.0001) with anincrease in the average BMI Z score of 0.270 SD (p=0.0001). 60% of children increased their BMI by 0.750 SD on average. Particularly in childrenwho avoid 4 or more allergens and children on OIT with hazelnut. There was no significant increase in the number of overweight children (6 be-fore OIT vs. 7 during OIT). Conclusion: Oral immunotherapy is accompanied by an increase in the BMI of allergic children, without an increase inthe incidence of overweight. It could be explained by the decrease in anxiety generated by food allergy, which would allow them to eat better.The caloric intake of products used for OIT is in itself non-significant. Oral immunotherapy could also act on the intestinal mucosa and its perme-ability, leading to better absorption of macro and micronutrients.

PE21-17 Evaluation of the effectiveness of subcutaneous immunotherapy with birch pollen extract for pollen-food allergy syndrome asso-ciated with soybean allergy

Masaaki Hamada1), Masakazu Kagawa2), Ichiro Tanaka1) (Department of Pediatrics, Yao Municipal Hospital, Japan1); Department of Clinical Re-search Center, Yao Municipal Hospital, Japan2))

Purpose: To investigate the efficacy of subcutaneous immunotherapy with birch pollen extract (Birch SCIT) for pollen-food allergy syndrome(PFAS) associated with soybean allergy.Method: Birch SCIT was introduced in 6 patients with PFAS caused by alder/birch pollen and soybeanallergy (Birch SCIT group). Another six patients with PFAS and soybean allergy did not receive Birch SCIT as a control group. Oral food chal-lenge test for soy milk was carried out in the Birch SCIT group and the control group. Results: In the Birch SCIT group, systemic adverse reac-tions occurred in 4 of 6 patients in the rapid escalation phase. The median intake of soy milk was 1.5 ml (quartile 1-2 ml) in the Birch SCIT groupand 5 ml (quartile 2-5 ml) in the control group, and there was no significant difference between the two groups. One year after the initiation oftherapy, the median intake of soy milk significantly increased to 150 ml (quartile 20-200 ml) in the Birch SCIT group, although none of the patientscould increase the intake in the control group. Conclusion: It was suggested that Birch SCIT could be the treatment for patients with PFAS andsoybean allergy despite concerns about systemic adverse reactions.

211

PosterSession

PE21-18 Real-world outcome of oral immunotherapy for food allergy

Miyuki Hoshi, Shingo Yamada, Mayumi Matsunaga, Kazutaka Nogami, Kana Hamada, Keigo Kainuma, Mizuho Nagao, Takao Fujisawa (AllergyCenter, National Hospital Organization Mie National Hospital, Japan)

Background: A number of randomized controlled trials have demonstrated that oral immunotherapy (OIT) for food allergy is effective in induc-ing desensitization to allergenic food and in preventing anaphylaxis by accidental exposure. However, long‐term data from the real‐world set-ting, assessing actual intake of allergenic food in daily life, are sparse.Method: A prospective nonrandomized trial. Eligible subjects were patientsaged 4-21 years with history of food-induced anaphylaxis who had objective immediate reactions at oral food challenge (OFC) to 800 mg of eggprotein (1/8 of a whole egg), 396 mg of milk protein (12 ml of milk), or 312 mg of wheat protein (12g of udon noodle) and positive specific IgE (sIgE)to the corresponding food allergens. The OIT was performed with a modified rush protocol; 3-4 week build-up phase to reach goal maintenancedose and subsequent maintenance phase. The goal dose was individually adjusted from small dose to full dose. Primary outcome was actual intakeof the allergenic food in daily life after 5 years of maintenance. A cross-sectional mail/web surveys for patients who underwent OIT from Decem-ber 2008 to October 2017 was conducted to investigate the outcomes. Results: A total of 242 patients were surveyed and 183 (76%) replied. Ofthem 72, 47 and 23 patients had continued maintenance egg, milk or wheat OIT for 5 years or more, respectively. Proportions of the patients whoate regular serving amount of egg, milk or wheat were 81%, 83% and 87%, respectively. Anaphylaxis in the build-up phase for milk, during mainte-nance phase for egg, dislike of egg and eosinophilic gastroenteritis by wheat were risk factors of not achieving the goal. Conclusion:We found fa-vorable long-term outcome of OIT comparable to short-term outcomes previously reported. Adverse events were the limiting factors against thesuccess.

212

PosterSession

Poster Session 22Immunotherapy 1

PE22-1 Sublingual immunotherapy treatment for nine-year-old boy suffering from allergic rhinitis causing sleep disorders and school ab-senteeism

Tamaki Ito1), Ikuo Okafuji1), Kiyoshi Kikuchi2), Satoru Tsuruta1) (Department of Pediatrics, Kobe City Medical Center General Hospital, Japan1);Children’s Rehabilitation, Sleep and Neurodevelopmental Medical Center, Hyogo Prefectural Rehabilitation Center Hospital, Japan2))

Background: Allergic rhinitis is known to have a significantly adverse effect on quality of life (QOL). Herein, we report a case of a child who wasdiagnosed with allergic rhinitis that caused sleep disorders but was improved via sublingual immunotherapy. Case: The case involved a nine-year-old boy, who had suffered from severe eczema in infancy, and year-round nasal discharge throughout childhood. After entering elementaryschool, he was often absent from school, owing to insomnia, malaise, headache, and dizziness; he had previously visited another sleep outpatientclinic; he was referred from there to our pediatric outpatient clinic, based on the diagnosis of suspected allergic rhinitis as a cause of sleep disor-der. At first consultation, it was noted that his inferior nostril was pale, exhibited strong congestion, and was filled with serous nasal discharge,causing frequent nose slips and mouth breathing in the patient. Blood tests showed total IgE levels of 218 IU/mL, Dermatophagoides pteronyssi-nus levels of 36.70 UA/mL, Dermatophagoides farinae levels of 40.70 UA/mL, and Japanese cedar levels of<0.10 UA/mL. A nasal dischargeeosinophil test revealed an E/N ratio of 0.93. In response to severe allergic rhinitis, antihistamines, leukotriene receptor antagonists, and nasalsteroids were administered, followed by conduction of sublingual mite immunotherapy with MiticureⓇ. After around three months of treatment,the patient could sleep well at night, without suffering from headache and dizziness, and attended school moreto the point where, by four months,he could attend school every day. Simultaneously, he felt that the treatment was effective and had improved his aptitude; he also reported that hisQOL has since improved, that he was satisfied with the treatment, and that his improved attitude has been remarked on at school. Conclusion:Allergic rhinitis persists in some children who visit medical institutions owing to insomnia, headache, and school refusal. Following appropriateevaluation, symptoms may be improved by including sublingual immunotherapy as part of the patient’s treatment.

PE22-2 Induction of an eosinophilic gastroenteritis occurred during sublingual immunotherapy with Japanese cedar pollen extract: acase report

Makoto Yasuda1), Shota Okamoto1), Takatoshi Nakajima2), Shigeru Hirano1) (Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefec-tural University of Medicine, Japan1); Department of Gastroenterology, Takatsuki General Hospital, Japan2))

Background: Eosinophilic gastrointestinal diseases (EGIDs) are characterized by dense infiltration of eosinophils in gastrointestinal tissues, result-ing in morphological and functional abnormalities of the gastrointestinal tract. EGIDs are divided into eosinophilic esophagitis (EoE) and eosino-philic gastroenteritis (EGE), depending on the involved gastrointestinal tract. We experienced an EGE case occurred during sublingual immuno-therapy (SLIT) with cedar pollen extract. Result: We encountered a 21-year-old male who had suffered for several years from severe allergicrhinitis caused by Japanese cedar (JC) pollen, house dust mite, and grass pollen with exacerbation mainly seen in April and May. In addition to al-lergic rhinitis, he had atopic dermatitis and food allergy to apples. He began to receive SLIT with daily administrations of standardized JC pollenextract according to the standard procedure. Ten days after initiation of the therapy, he felt mild abdominal pain. His symptoms such as severeabdominal pain and frequent vomiting gradually increased and he visited the emergency unit of our hospital 21 days after starting SLIT. Sincecomplete blood cell examination including eosinophil count was normal, he was told to go home with some prescription drugs. However, his symp-tom did not get better after one week passed. He visited the gastroenterology of another hospital. Blood cell examination revealed increase ineosinophil count, and he was suspected of an eosinophilic gastrointestinal disease. Upper and lower gastrointestinal endoscopies were performedtogether with biopsies from some lesions. As biopsy specimens showed severe eosinophil infiltration in each organ, he was finally diagnosed as anEGE due to SLIT for JC pollinosis. Fortunately, he had recovered from his illness only by quitting SLIT. Conclusion:We will report the first case,to our knowledge, of EGE in a young adult that occurred during SLIT for JC pollinosis.

PE22-3 Mastocytosis and tryptase in hymenoptera venom allergy: real world data from the United States

Dilawar Khokhar1), Charles F Schuler1,2), Sofija Volertas1,7), Yunshen Jiao3), Onur Baser4), Huseyin Yuce5), Jenny Montejo1,6), Cem Akin1) (Division ofAllergy and Clinical Immunology, University of Michigan, USA1); Mary H Weiser Food Allergy Center, University of Michigan, USA2); ColumbiaData Analytics, USA3); MEF University, Turkey4); Department of Mathematics, New York City College of Technology, USA5); Mayo Clinic, USA6);Division of Rheumatology, Allergy and Immunology, University of North Carolina, USA7))

Rationale: Mastocytosis is a risk factor for hymenoptera venom anaphylaxis and current guidelines recommend measuring tryptase in Hy-menoptera venom allergy (HVA) patients. This data is based largely on European single center studies and the rate of mastocytosis in the UnitedStates (US) HVA population is not known. Methods: A retrospective study of 161 patients undergoing venom immunotherapy (VIT) between2015 and 2018 at the University of Michigan Allergy clinic was conducted. Variables assessed included the original reaction’s nature and severity,reactions to VIT, tryptase level, and bone marrow biopsy results. Statistical analyses included bivariate and chi-squared correlations, followed bylinear or logistic regression as appropriate. The IBM Watson Database consisting of insurance claims from approximately 40 million patients wasqueried to identify patients with a diagnosis of HVA and/or mastocytosis. Results: In the University of Michigan cohort, 2.6% of patients werefound to have underlying mast cell disease. Tryptase level did not correlate with severity of the initial reaction but was found to be higher in pa-tients with systemic reactions to VIT. In the IBM Watson database, 218,814 HVA patients were identified and 59 of these also carried a diagnosisof mastocytosis. Compared to the general population, there was a 12-fold increase in mastocytosis prevalence in patients with HVA (p<0.0001).Conclusion: Our data suggest a lower rate of mastocytosis in the US population than previous reports. We observed that patients with HVA hadsignificantly greater rates of mastocytosis over the general population however there was no correlation between tryptase level and severity ofreactions.

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PosterSession

PE22-4 Efficacy and safety of allergen immunotherapy for allergic rhinitis with autoimmune disease

Kazuki Fujioka, Akiko Kasahara, Makoto Wada, Masataka Kohno, Yutaka Kawahito (Department of Inflammation and Immunology, Kyoto Pre-fectural University of Medicine, Japan)

Objectives: Allergen immunotherapy (AIT) is the only causative treatment that modifies the natural history of allergic diseases. However, sincethe overall effect on the immune system has not been elucidated, there is a concern that unfavorable effects will be exerted on patients with auto-immune diseases (AID), and the number of AID patients receiving AIT is not large. Therefore, there has been few observations of efficacy againstallergic symptoms and changes in the activity of background AID, when AIT was applied to these AID patients. We examined the efficacy andsafety of AIT for allergic patients with autoimmune diseases.Method: AID patients who received AIT at our hospital were extracted from medi-cal records and their clinical course was retrospectively investigated. Result: There were 13 AID patients who received AIT at our hospital, withan average age of 58.3 years. The breakdown was 8 in RA, 1 in PM with SSc, 1 in Sjogren syndrome, 1 in EGPA, 1 in Spondyloarthritis, and 1 ineosinophilic fasciitis. All patients received sublingual immunotherapy for allergic rhinitis (11 in Japanese cedar, 2 in mites). Four patients haddropped out due to adverse events (1 case of nasal symptom, 3 cases of oral discomfort). Efficacy was evaluated in 6 cases, and 5 cases showed asignificant improvement of symptom scores in the JRQLQ questionnaire. Of all cases, including those discontinued, 3 cases worsened AID symp-toms, but none of them had been determined to have a causal relationship with AIT. Conclusion: AIT is considered to be a safe and effectivetreatment for allergic rhinitis patients with autoimmune diseases.

PE22-5 Sublingual immunotherapy improved nasal symptoms and allergen-specific nasal and skin reactivity in house dust mite-inducedperennial allergic rhinitis patients

Sawako Masuda, Satoko Usui (Department of Otorhinolaryngology, National Hospital Organization Mie National Hospital, Japan)

Background: The efficacy of sublingual immunotherapy (SLIT) on allergic rhinitis is mainly evaluated by changes in nasal symptoms. Method:Twenty-three patients with house dust mite (HDM)-induced perennial allergic rhinitis (5 males and 8 females, aged from 5 to 60 years old) re-ceived SLIT with HDM extract for more than one year. Total nasal symptom scores (TNSS), eosinophil count in the nasal secretion, nasal provoca-tion tests with house dust, skin prick tests with HDM, and specific IgE to HDM in serum was evaluated before immunotherapy and one year afterstarting the therapy. Results: At one year after starting the treatment, TNSS significantly decreased from baseline (p<0.05). Significant reductionin nasal sensitivity to house dust (p<0.01) and skin reaction to HDM (p<0.01) was also observed. No significant differences were detected in nasaleosinophilic count. Specific IgE to HDM in serum significantly increased from baseline after six months of treatment (p<0.01), and significantly de-creased after one year (p<0.05). The significant correlation was observed between the change of TNSS from baseline to one year and the changeof nasal sensitivity to house dust from baseline to one year. Conclusion: One-year of HDM-SLIT not only improved nasal symptom but also modu-lated allergen-specific nasal and skin reactivity in the patients with HDM-induced perennial allergic rhinitis.

PE22-6 Efficacy of sublingual immunotherapy for house dust mite allergic rhinitis in children

Kayoko Kawashima1), Masashi Yamamoto1), Mika Okuno1), Yuri Takaoka2), Yukinori Yoshida2), Makoto Kameda2) (Department of Otorhinolaryngol-ogy, Osaka Habikino Medical Center, Osaka Prefectural Hospital Organization, Japan1); Department of Pediatrics, Osaka Habikino Medical Center,Osaka Prefectural Hospital Organization, Japan2))

Background: Sublingual immunotherapy (SLIT) was added to the list of treatments for pediatric allergic rhinitis in children under the age of 12years in Japan in 2018. At our center, the efficacy of sublingual immunotherapy for perennial allergic rhinitis induced by house dust mites initi-ated in children 15 years old and under in 2018 was investigated. Methods: The subjects were 44 children had pediatric allergic rhinitis. Housedust mite(HDM) SLIT was started during the summer vacation from July to August in 2018. Thirty-seven (84.1%) of these children also had otherallergies. After the start of the SLIT, the children and their parents were asked to write in a diary the daily symptoms and medications used.Regular assessments set to match school vacations were then performed during the 2018 winter vacation (December-January), 2019 spring vaca-tion (March-April), and the 2019 summer vacation (July-August). In accordance with the practical guideline for the management of allergic rhini-tis, the symptom and drug scores were the means of the scores recorded in the symptom diaries for one week before visiting the hospital on theday of assessment. On the day of the regular assessment, a questionnaire survey using the Japanese Allergic Rhinitis Standard Quality of LifeQuestionnaire (JRQLQ No. 1) was also administered, and house dust mite nasal provocation tests were performed as objective tests. Results: Twochildren dropped out after one year. Compared with before the start of sublingual immunotherapy in the summer of 2018, the total nasal symp-tom medication score was significantly lower in the summer of 2019. Although seasonal fluctuations were seen in the symptom score and qualityof life score on the JRQLQ No. 1, the nasal score was significantly lower in the summer after one year. Reactivity in a nasal provocation test with ahouse dust disc after one year also decreased. Conclusion: HDM SLIT for pediatric allergic rhinitis was shown to have short-term efficacy in chil-dren with other concurrent allergic diseases.

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PosterSession

PE22-7 A novel immuntherapy to airway allergy

Mingi Chang, Yu Shen Hsu, Annie Pai (Advagene Biopharma Co., Ltd., Taiwan)

The increasing allergic rhinitis/rhinoconjunctivitis, allergic asthma and food allergy has been contributed to environment and/or genetics under-lying immunity. Allergic therapies involve two major categories, symptomatic control via small compounds, e.g. antihistamine and immunother-apy by biologics, such as allergen. Only immunotherapy may provide long term prevention to allergy but lengthy treatment often hindering thepatient’s compliance. The LTh(αK) is a detoxified enterotoxin from E Coli with immunomodulatory potential demonstrated in two clinical trialsconducted by Advagene. Preclinical studies have showed that intranasal treatment of LTh(αK) limited the clinical manifestations of subsequentallergen induced allergic responses. In the allergen cotreatment model, sublingual treatment of allergens in conjunction with LTh(αK) via in-tranasal route not only enhancing the allergen-specific IgG and IgA, but also drastically reducing the frequencies of treatment. In addition to pro-phylactic model, therapeutic models also came out with comparable outcomes. Due to significant finding on animals, a phase Ib/IIa clinical trial onallergic rhinitis has been initiated. In this trial, three dosing arms of LTh(αK) are giving to volunteers with rhinitis weekly for a total of three con-stitutive doses and follow for additional 6 weeks. The TNSS is set as primary endpoint. The second cohort has been completed and final data un-blind is set to the fourth quarter of 2020.

PE22-8 Safety and efficacy of house dust mite subcutaneous immunotherapy (interim analysis of post-marketing surveillance from 2016to 2019)

Hiroki Matsuhara, Takeru Sugawara, Yuriko Maekawa, Remi Hashimoto, Keiichi Taniguchi (Torii Pharmaceutical Co., Ltd., Japan)

Background: Allergen Extract Standardized HDM“TORII”(Torii, Japan/ALK, USA) is a house dust mite (HDM) allergen extract for subcutane-ous immunotherapy (SCIT) and is available for HDM-induced allergic rhinitis (AR) and allergic asthma (AA) in Japan. Post-marketing surveillance(PMS) has been initiated to investigate the safety and efficacy of long-term administration (24 months) in patients with AR and AA. Methods:Eighty patients (younger than 15 years: 56.3%) were included for safety analysis in this evaluation (data lock: December 25th, 2019). We assessedadverse drug reactions (ADRs) and a global evaluation (Much better, Better, The same, Worse, Much worse) of AR and AA. Results: Sixty-ninepatients had never undergone HDM-specific SCIT, and 11 patients had switched from house dust (HD) -specific SCIT. In new patients, the initialdose was 0.00023 JAU, and the maintenance dose was mainly 500 JAU. In patients who had switched from HD-specific SCIT, the initial dose was0.00520 JAU. Sixty-four ADRs occurred in 34 patients. No serious ADRs were reported. The most common ADRs were urticaria (21.3%) and ana-phylaxis (10.0%). Global evaluation of both AR and AA showed improvements (Much better+Better) before administration (AR: approximately80% from 6 months, AA: approximately 70% from 12 months). Conclusion: This interim analysis does not identify new safety concerns. In real-lifesettings in Japan, Allergen Extract Standardized HDM“TORII”improves overall symptoms in patients with AR and AA during treatment.

PE22-9 Safety and efficacy of Japanese cedar pollen sublingual immunotherapy tablet under actual use condition (interim analysis ofpost-marketing surveillance from 2018 to 2019)

Satoko Kobayashi, Yuriko Maekawa, Hiroko Honda, Eiji Horikawa, Chiyoko Kunishima, Noriaki Nishino (Torii Pharmaceutical Co., Ltd., Japan)

Background: Japanese cedar pollen (JCP) sublingual immunotherapy (SLIT) tablet (5,000 JAU Torii, Japan/ALK, Denmark) is a freeze-dried, fast-dissolving lyophilisate formula. It has been approved for the treatment of Japanese cedar pollinosis since 2017. Post-marketing surveillance of theJCP SLIT tablets has been initiated to investigate the safety and efficacy among patients with Japanese cedar pollinosis under actual use condi-tion actual treatment from August 2018 to December 2023. Here, we report the interim results of this surveillance from August 2018 to Septem-ber 2019.Methods: In this surveillance, 500 patients who have never undergone JCP SLIT treatment were observed for 2 years. The safety pro-file of these patients was assessed during adverse events. Efficacy was assessed in 2 JCP seasons by evaluating the severity, symptom score, gen-eral state in JRQLQ, and global evaluation. The data sets were obtained for 116 cases in the first season evaluation that was fixed until September26, 2019. Results: No serious adverse drug reactions (ADRs) were reported. ADRs occurred only in 12 out of 116 patients (10.3%). The most fre-quent ADRs were mild local reactions, such as throat irritation (5.2%), ear pruritus (3.4%), mouth swelling, oral pruritus, and cough (2.6% each).The general state in JRQLQ was analyzed using the data of 69 patients who were assessed in both baseline and in the first season after treatment.Out of these 69 patients, 59 patients (85.5%) showed significant improvement compared to before treatment. A total of 101 patients were sub-jected to the global evaluation. Out of these 101 patients, 95 patients (94.1%) showed improvements (Much better+Better). Conclusion: In the in-terim results of this surveillance, no safety concerns were found. Moreover, more than 80% of the patients showed an amelioration of symptoms inJapanese cedar pollinosis in the first season.

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PosterSession

PE22-10 The efficacy of SQ HDM sublingual immunotherapy tablets in patients with HDM-induced allergic rhinitis in Japan (interimanalysis of post-marketing surveillance from 2016 to 2019)

Yuriko Maekawa, Remi Hashimoto, Keiichi Taniguchi, Hiroki Matsuhara, Chiyoko Kunishima, Noriaki Nishino (Torii Pharmaceutical Co., Ltd., Ja-pan)

Background: The SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablets (10,000JAU Torii, Japan/6 SQ-HDM, ALK, Denmark)have been approved for the treatment of HDM-induced allergic rhinitis (AR) in Japan. Post-marketing surveillance (PMS) of the SQ HDM SLIT-tablets has been initiated to investigate the safety and efficacy of long-term administration (3 years) in patients with HDM-induced AR. In thisanalysis, we report the efficacy at third interim analysis based on data collected from 2016 to 2019. Method: In this analysis, we performed an in-terim analysis of 684 patients fixed from the start of the survey to September 2019. Effectiveness was evaluated using the general state score ofJapanese Allergic Rhinitis Standard Quality of Life Questionnaire (JRQLQ) No1 (0: fine to 4: crying) and the global evaluation (much better, better,the same, worse, much worse). Improvement was defined score 0 plus 1 in the JRQLQ and much better plus better in the global evaluation asoverall symptom. Result: 684 patients were included the children under 15 years old (231 patients, 33.8%), the adult (438 patients, 64.0%) and theelderly over 65 years old (15 patients, 2.2%). The major complications were bronchial asthma (79 patients, 11.6%) and Atopic dermatitis (79 pa-tients, 11.6%). The JRQLQ and global evaluation were improved over time for two years of treatment in approximately 80% of patients. The chil-dren patients also showed improvements in both evaluations in the same manner. Conclusion: In the real-world clinical setting in Japan, SQ HDMSLIT-tablets improved QOL and overall symptom depending on treatment period regardless of age stratification.

PE22-11 Actual conditions of dual SLIT with Japanese cedar pollen sublingual immunotherapy products and SQ house dust mite sublin-gual immunotherapy tablet in Japan

Yuriko Maekawa, Hiroki Matsuhara, Satoko Kobayashi, Eiji Horikawa, Keiichi Taniguchi, Noriaki Nishino (Torii Pharmaceutical Co., Ltd., Japan)

Background: In Japan, a large proportion of allergic rhinitis (AR) patients are sensitized to both, Japanese cedar pollen (JCP) and house dust mites(HDM). Although JCP sublingual immunotherapy (SLIT) droplets and tablets, and SQ HDM SLIT tablet are available in clinical practice in Japan,the safety and efficacy of their co-administration, i.e. dual SLIT, has not been investigated. Therefore, we investigated the actual conditions of dualSLIT with JCP and HDM SLIT ptoducts based on post-marketing surveilances.Method: This evaluation was based on three post-marketing sur-veilances of SQ HDM SLIT tablets (715 patients), JCP SLIT tablets (116 patients) and JCP SLIT droplets (1225 ptients). We investigated the ad-verse drug reactions (ADRs) and quality of life using Japanese Allergic Rhinitis Standard Quality of Life Questionnaire (JRQLQ) No.1 in the pa-tients who treated with dual SLIT of JCP and HDM. Result: Each surveillance included 93, 23, and 18 patients administered with dual SLIT, re-spectively (<15 years : 50/134 patients). Most patients preceded either JCP or HDM SLIT product, followed by addition of the other SLIT product.ADRs occurred 15 events, 6 events and 1 event in each surveillance, respectively. Most ADRs were mild and local reactions, such as mouth swel-ling and oral discomfort and related to the application site. The JRQLQ showed improvement over time. Conclusion: This evaluation does notidentify new safety concerns in patients of dual SLIT. In a real life setting in Japan, the dual SLIT of JCP and SQ HDM SLIT products conductedunder the supervision of health provider is seemed to be safe and efficacious.

PE22-12 Efficacy and safety of dual sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergic rhinitis

Tatsuya Fujii1,2), Yoshiaki Kitamura2), Seiichiro Kamimura2), Noriaki Takeda2) (Department of Otolaryngology, JA Kochi Hospital, Japan1); Depart-ment of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan2))

Background:Many patients with allergic rhinitis (AR) are sensitized to multiple allergens, and the most common coexisting seasonal and peren-nial AR are Japanese cedar (JC) pollinosis and house dust mite (HDM) AR in Japan. Although the efficacy and safety of sublingual immunotherapy(SLIT) for each AR are well-known, there is insufficient evidence of dual SLIT. In this study, we investigated the efficacy and safety of dual SLITwith JC pollen and HDM for coexisting JC pollinosis and HDM AR. Methods: A non-randomized controlled study was conducted in 25 patientswith coexisting JC pollinosis and HDM AR. Sixteen out of these patients received dual SLIT for JC pollen and HDM, another nine patients re-ceived SLIT monotherapy for JC pollen. We compared nasal symptoms of JC pollinosis during JC pollen dispersal period between pre-SLIT andpost-SLIT using classification of the severity of AR symptom, and also compared nasal symptoms of HDM AR from November to December whenHDM AR symptoms being exacerbated between pre-SLIT and post-SLIT using Japanese Allergic rhinitis QOL Standard Questionnaire No.1. Inaddition, we evaluated the efficacy of dual SLIT by comparing nasal symptoms during JC pollen dispersal period with JC pollen SLIT monother-apy. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. Results: Dual SLIT with JCpollen and HDM significantly improved nasal symptoms of both of JC pollinosis and HDM AR compared with pre-SLIT in patients with coexistingJC pollinosis and HDM AR. Moreover, dual SLIT significantly improved nasal obstruction during JC pollen dispersal period compared with JC pol-len SLIT monotherapy. Eight out of sixteen dual SLIT patients experienced adverse events, but no serious events were observed. Conclusion:These findings suggested that dual SLIT was effective, safe and better than JC pollen SLIT monotherapy in reducing nasal obstruction during JCpollen dispersal period in patients with coexisting JC pollinosis and HDM AR.

216

PosterSession

PE22-13 Dose reduction in inhaled corticosteroid of sublingual immunotherapy during 3 years for allergic asthma with cedar pollinosis

Kyohei Morita1), Chie Yoshimura1), Shinichi Sumimoto2), Hiroki Ikeda3), Toshitaka Morishima5), Erika Toyokura1), Kenta Nishi4), Ryoichi Ishikawa1),Masato Taki1), Hwang Moonhee1), Yasuo Nishizaka1) (Department of Respiratory Medicine, Japanese Red Cross Osaka Hospital, Japan1); Depart-ment of Pediatrics, Japanese Red Cross Osaka Hospital, Japan2); Ikeda-jibika (E.N.T. clinic), Japan3); Department of Respiratory Medicine, GraduateSchool of Medicine, Kyoto University, Japan4); Cancer Control Center, Osaka International Cancer Institute, Japan5))

Background: More than 40% of adult asthma patients have comorbid allergic rhinitis. The exacerbation of asthma symptoms due to cedar polli-nosis often results in the need for increased doses of inhaled corticosteroid (ICS). There are no reports on the dose-reduction of ICS in sublingualimmunotherapy (SLIT) for patients with asthma complicated by cedar pollen allergy. Objective: To investigate the dose of ICS used over time inpatients with asthma complicated by cedar pollinosis who received either add-on SLIT with pharmacotherapy or the standard treatment. Meth-ods: Of patients with asthma complicated by pollinosis who started add-on SLIT with pharmacotherapy and those who received the standardtreatment between May and December in 2015 and 2016 (the non-dispersal period of cedar pollen), patients who could continue the treatment for3 years were retrospectively examined. The dose of ICS (fluticasone propionate [FP] conversion) used in 1, 2, and 3 years was compared. Results:The add-on SLIT group comprised 36 patients with a mean age of 51.5±14.3 years, including 26 women (72%), and the baseline ICS (FP) dose was533.3±293.2 µg. The standard treatment group comprised 38 patients with a mean age of 48.0±18.2 years, including 27 women (71%), and thebaseline ICS (FP) dose was 597.4±294.2 µg. Up to 3 years of follow-up, add-on SLIT group significantly decreased in ICS dose compared with stan-dard treatment group. (1 year: 516.7±334.4µg vs 585.5±285.4µg, -4.8 (-138.1 to 128.4) p=0.94. 2 years: 475.7±365.3µg vs 653.9±312.5µg, -114.22(-247.5 to 19.0) p=0.09. 3 years: 369.4±378.3µg vs 614.5±376.4µg, -180.9 (-314.2 to -47.6) p=0.008). Conclusions: In the third year, addition of SLIT tostandard asthma therapy provides dose reduction in ICS compared with pharmacotherapy alone in patient with both cedar pollinosis and asthma.

PE22-14 Safety of dual sublingual immunotherapy with house dust mite and Japanese cedar pollen tablets

Naofumi Suzuki1), Hisashi Nishimori1), Jun Horie1), Atsushi Kohso1), Tomoya Harada1), Hirotoshi Makino1), Katsuhiko Ito1), Keiko Yamaguchi1),Yusuke Omori1), Hodaka Ohta1), Kenji Sugiyama1), Eri Suzumura2), Takao Fujisawa3) (Department of Pediatrics, Mie Prefectural General MedicalCenter, Japan1); Department of Otolaryngology, Mie Prefectural General Medical Center, Japan2); Allergy Center, National Hospital OrganizationMie National Hospital, Japan3))

Background: In Japan, sublingual immunotherapy (SLIT) tablets of Japanese cedar pollen (JCP) have been available since 2014, and those ofhouse dust mite (HDM) have been available since 2015. Efficacy of the SLIT with HDM and JCP has been well described. Need for concomitantuse of the both tablets, dual SLIT, is not small for patients who have allergies to the two most common allergens. However, safety of dual SLIThas not been established. Methods: Data were reviewed from electric medical records of allergic rhinitis patients who received both HDM andJCP tablets from January to December 2019 in Mie Prefectural General Medical Center, Japan. The aim is to evaluate the safety of dual SLIT, sowe analyzed the frequency of adverse events (AEs) and the rate of cessation of therapy. Results: A total of 66 children (male 44, female 22, agerange 4 to 16 years, median age 8 years) were enrolled in this study. 61 children (92.4%) had bronchial asthma (BA) and 37 children (56.0%) had al-lergic conjunctivitis. The median value of serum total IgE at enrollment was 839 IU/ml. (1 child’s data was missed) The median value of peripheraleosinophil count at enrollment was 442/µl. (1 child’s data was missed) The median duration of therapy at the end of December 2019 was 2.9months. 48 children (72.7%) had AEs. The majority of AEs were mild in severity and were able to be observed without any medication therapy.The most frequent AE was oral pruritus. (39 children, 59.1%) Most children had AEs soon after they started SLIT, and only 1 child (1.5%) had AEsboth HDM and JCP tablets. 6 children (9.1%) interrupted the therapy because of AEs or uncontrolled BA or uncontrolled atopic dermatitis. Con-clusion: Dual sublingual immunotherapy with HDM and JCP tablets is a safe and well-tolerated.

PE22-15 Medication compliance of sublingual immunotherapy in patients with house dust mite induced allergic rhinitis in Japan: a retro-spective database study

Yoshie Hongo1), Martin Rees2), Yuki Kado3), Manami Yoshida1), Shinzo Hiroi1), Efstrathios Karagiannis2) (Medical Affairs Department, Shionogi &Co., Ltd., Japan1); Stallergenes Greer, France2); IQVIA Solutions Japan K.K, Japan3))

Background: Sublingual immunotherapy (SLIT) has been considered as a curative therapy for allergic rhinitis (AR). Several years of treatmentare recommended and medication compliance is crucial for achieving the long-term therapeutic benefits. However, medication compliance in clini-cal practice in Japan is uncertain. In this study, we evaluated the medication compliance of SLIT for house dust mite (HDM)-induced AR in Japan.Methods:We analyzed prescription data from an IQVIA Rx Database (January 2015-October 2019), covering over 18% of the whole external pre-scriptions in Japan. Patients prescribed SLIT tablets [house dust mite sublingual tablets (Actair and/or Miticure)] at least once were extractedfrom the database. The first prescription date of SLIT tablets was defined as index date (ID), and observation period (OP) was defined as the expo-sure period from ID of any of following prescription, SLIT tablets, AR medication, and asthma medication. Only patients with records of ≧1 yearbefore the ID, without severe asthma and COPD were included in the analysis. Medication compliance to SLIT was measured using the propor-tion of days covered (PDC), i.e., it was calculated as total number of prescription days of SLIT tablets/total number of days undergoing SLIT inthe OP. Results: A total of 10969 individuals were prescribed SLIT tablets at least once, and 5278 were fulfilled the above-mentioned criteria. Of5278 patients, 3550 (67%), 1096 (21%), and 448 (8%) were between 5 to 18, 30 to 55, and 18 to 30 years old, respectively. Mean PDC in the entire OPwas 96%, and those in OP from 0 to 6, 6 to 12, 12 to 18, 18 to 24, 24 to 36, and after 36 months were 98%, 94%, 94%, 94%, 92%, and 92%, respectively.Conclusion:Most of the patients receiving SLIT were children and adolescents. The medication compliance was generally good, and it indicatedthat SLIT is well-accepted treatment for patients with HDM-induced AR in Japan.

217

PosterSession

PE22-16 Efficacy and safety of sublingual immunotherapy in patients with allergic rhinitis induced by house dust mites

Satoko Hamada1,2), Yoshiki Kobayashi1,2), Akihiro Shimamura1), Daiki Sakamoto1), Mikiya Asako1,2), Hiroshi Iwai1) (Department of Otorhinolaryngol-ogy, Kansai Medical University, Japan1); Allergy Center, Kansai Medical University, Japan2))

Background: Allergic rhinitis (AR) is a major chronic inflammatory disease of the respiratory tract and frequently coexists with asthma andother allergic diseases. Allergy immunotherapy (AIT) is recognized as an effective treatment for allergic rhinitis and respiratory allergic disease.In Japan, sublingual immunotherapy (SLIT) tablets have been available for the treatment of allergies to house dust mites (HDMs) since 2015. Theaim of this study was to evaluate the safety and efficacy of SLIT for both upper and lower airway inflammation in patients with HDM-inducedAR.Methods: A total of fifty patients with HDM-induced AR were retrospectively analyzed. All patients were treated with 6 SQ-HDM SLIT tab-lets for more than 2 years. The total nasal symptom medication score (TNSMS), and quality of life (QOL) score were assessed. Serum Dermato-phagoides farinae specific IgE and IgG4 expression levels, fractional exhaled nitric oxide (FeNO) and spirometry were also assessed. All outcomeswere measured before treatment, and at 1 and 2 years after the onset of treatment. Safety was also evaluated based on the occurrence of adverseevents (AEs). Results: The observed AEs were mainly mild and localized. No serious side effects, such as anaphylaxis, were observed. TheTNSMS scores were significantly reduced after 1 and 2 years of treatment. The QOL scores for activities of daily life were also improved after 1and 2 years of treatment. The mean FeNO level in patients without asthma was higher than the normal level (25ppb). The patients with FeNOlevel over 25ppb before treatment showed a significant decrease in level at 1 year after the onset of treatment. Conclusion: SLIT was effective inimproving upper airway systems associated with HDM-induced AR, and may also be effective for treating lower airway inflammation.

218

PosterSession

Poster Session 23Immunotherapy 2

PE23-1 Genome-wide transcriptome and copy number variation analysis for sublingual immunotherapy

Osamu Kaminuma1,4), Minoru Gotoh1,2), Akihiro Nakaya1,3), Mayumi Saeki1), Tomoe Nishimura1), Noriko Kitamura1), Nobumasa Watanabe1),Kimihiro Okubo1,2), Takachika Hiroi1) (Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Japan1); Department ofOtorhinolaryngology, Nippon Medical School, Japan2); Department of Genome Informatics, Osaka University, Japan3); Department of DiseaseModel, Hiroshima University, Japan4))

Background: Regardless of the strong therapeutic potency, the principal mechanisms underlying the efficacy of allergen immunotherapy largelyremain unknown. We investigated the genomic DNA structural variations related with the efficacy of sublingual immunotherapy (SLIT) againstpatients with Japanese cedar pollinosis (JCP). Methods: Following 2-year SLIT with the cedar pollen extract, JCP patients were classified intohigh-responder (HR), non-responder (NR), and the other groups. In addition to genome-wide copy number variation (CNV) analysis, microarray-based transcriptome analysis for CD4+ T cell- and basophil-expressing genes were performed to compare HR and NR groups. Results: An apopto-sis pathway was extracted both in CD4+ T cells and basophils as a SLIT efficacy determinant by the multivariate pathway analysis for microar-ray data. Taste receptor type 2 member 43 (TAS2R43) in CD4+ T cells and D4, zinc, and double plant homeodomain fingers family 2 in basophilswere identified as CNV-related and differentially expressed genes between HRs and NRs. Stimulation-induced expression of IL-4 in human CD4+

T cells was augmented by TAS2R agonists. Conclusion: CNV-related differential gene expression in CD4+ T cells and basophils may be relatedwith the efficacy of SLIT against JCP patients.

PE23-2 Changes of immunological response with subcutaneous immunotherapy for Japanese cedar

Tomoyuki Asaumi1), Sakura Sato2), Noriyuki Yanagida1), Hiroki Matubara3), Satoko Kobayashi3), Chiharu Fukano3), Katsuyo Ohashi-Doi3),Motohiro Ebisawa2) (Department of Pediatrics, National Hospital Organization Sagamihara National Hospital, Japan1); Department of Allergy,Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan2); Torii Pharmaceu-ticals Co., Ltd., Japan3))

Background: Immunological response of subcutaneous immunotherapy (SCIT) for Japanese cedar is not fully clarified yet. Therefore, we investi-gated the immunological response with SCIT for Japanese cedar. Method: Eleven patients have been treated with 3 year SCIT for Japanese ce-dar at Sagamihara National Hospital in 2013-2014. Rush SCIT was used as a 5-day introduction and reach to 400 JAU as the target dose. The doseon the last day of admission was applied to the maintenance dose at outpatient clinic. Symptoms of nose and eyes (Symptom score) during thescattering of Japanese cedar pollen and immunological changes were investigated. Japanese cedar specific antibodies (IgE and IgG4) were meas-ured by ImmunoCAP. To detect the change of allergen presenting ability in B cells, IgE－allergen－CD23 complexes in serum was measured bya cell-free, Enzyme-linked Immunosorbent assay (ELISA)-based FAB (ELIFAB) assay. Results: Median age (IQR) of subjects was 8 (6-10) yearsold. Three patients (27%) were comorbid with atopic dermatitis, and 5 patients (45%) bronchial asthma. Before starting SCIT, total IgE was 373(75－2870) kIU/L, and Japanese cedar specific IgE was 77.2 (15.4－528) kUA/L. Symptom score improved significantly and persistently from theyear after treatment. Japanese cedar specific IgE did not change after 3 years of treatment. Japanese cedar specific IgG4 increased significantlyand persistently after 1 month of treatment. IgE－allergen－CD23 complexes decreased significantly after 3 years of treatment. Conclusion:Japanese cedar specific IgG4 increased, and binding ability to CD23 decreased in SCIT, which may suggest increase of blocking factors as amechanism of action.

PE23-3 The safety of SQ HDM sublingual immunotherapy tablets in patients with HDM-induced allergic rhinitis in Japan (interim analy-sis of post-marketing surveillance from 2016 to 2019)

Shiori Saito, Yuriko Maekawa, Remi Hashimoto, Keiichi Taniguchi, Chiyoko Kunishima, Noriaki Nishino (Torii Pharmaceutical Co., Ltd., Japan)

Background: The SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet (10,000JAU Torii, Japan/ALK, Denmark) has been ap-proved for the treatment of HDM-induced allergic rhinitis (AR) in Japan. Post-marketing surveillance (PMS) of the SQ HDM SLIT tablets has beenconducted to investigate the safety and efficacy of long-term administration (3 years) in the patients with HDM-induced AR. In this study, we re-port the results of the safety assessment performed during the third interim analysis. Method: This PMS was initiated in July 2016 and will beconducted until December 2022. In the present study, we performed an interim analysis by using the data from 715 cases that were fixed fromthe start of the survey to September 2019. Result: A total of 715 patients (mean age, 27.3 years; approximately 50% were <20 years of age) wereincluded in this safety analysis (6 months: 715 patients, 12 months: 478 patients, 24 months: 223 patients, 36 months: 2 patients), out of which 198patients showed concomitant diseases, such as bronchial asthma, atopic dermatitis, and allergic conjunctivitis. The incidence of adverse drug reac-tions (ADRs) was 16.5% (118 out of 715 patients). In stratified analysis, the incidence of ADRs in children, adults, and the elderly was 14.5% (35 outof 241 patients), 17.5% (80 out of 458), and 18.8% (3 out of 16), respectively. There was no statistical difference (p=0.056, Fisher’s exact test) in the in-cidence of ADRs in the patients with concomitant diseases. In particular, the incidence of ADRs in patients with bronchial asthma was 14.8% (15out of 83 patients). Most ADRs were local reactions occurring in the oral cavity and pharynx. Conclusion: In this interim analysis of a PMS study,we did not identify any new safety concerns. We will thus continue to collect safety information in order to promote proper use of the SQ HDMSLIT tablets.

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PosterSession

PE23-4 Development of a novel Cry j 1 allergoid using chemical modification

Takeru Sugawara, Keisuke Suzuki, Koji Fujinami, Katsuyo Ohashi-Doi (Research Laboratory, Torii Pharmaceutical Co., Ltd, Japan)

Background: Allergy immunotherapy (AIT) is the only disease modifying treatment for IgE-mediated allergy. Since AIT products were firstlaunched for Japanese cedar (JC) pollinosis, subcutaneous treatment with crude allergen extracts has been associated with a risk of anaphylaxis inclinical practice. Therefore, the generated Cry j 1 allergoids (major JC allergen) with lower IgE-binding (low allergenicity) compared to modifiedCry j 1 allergen or JCP pollen extract would be a candidate substance for next generation of AIT. The aim of this study was to produce and char-acterize an allergoid of chemically modified Cry j 1.Method: Cry j 1 allergoid was generated by conjugating purified native Cry j 1 (nCry j 1) withpullulan (p-Cry j 1) followed by denaturing in guanidine hydrochloride (Dn p-Cry j 1). The allergenicity was evaluated by IgE-binding, EXiLE1) andbasophil activation test. Effective IgE-binding value was calculated from dose-response curves compared to nCry j 1. To evaluate immuno-genecity, proliferation of splenocytes obtained from nCry j 1 or Dn p-Cry j 1 sensitizedmice was measured. Data were expressed as IC50 (IgE-binding), EC50 (EXiLE), expression of CD203c and BrdU incorporation (cell proliferation). Results: Reduced allergenicity was observed in IgE-binding (nCry j 1: 6.02 ng/mL, Dn p-Cry j 1 : 1830 ng/mL) and EXiLE assay (nCry j 1 : 0.17 ng/mL, Dn p-Cry j 1 : 3230 ng/mL). The percentage ofCD203c expression was more than 90% for nCry j 1 and less than 2% for Dn p-Cry j 1 at maximum response (10 ng/mL Cry j 1). Splenocyte prolif-eration was equivalent to nCry j 1 and Dn p-Cry j 1 (nCry j 1: 6.19×105 counts per second (CPS), Dn p-Cry j 1: 4.74×105 CPS). Conclusion: Wecould generate a Cry j 1 allergoid with high reproducibility by conjugating with pullulan followed by denaturation. The Dn p-Cry j 1 allergoidshowed lower allergenicity than nCry j 1. 1) R. Nakamura et al., Allergy (2010).

PE23-5 Sublingual immunotherapy with Japanese cedar pollen extract induces apoptosis of memory CD4+ T cells

Hiroyuki Arai1), Hideaki Kouzaki1), Atsushi Yuta1,2), Takeshi Shimizu1) (Department of Otorhinolaryngology, Shiga University of Medical Science,Japan1); Yuta Clinic, Japan2))

Background: Allergen immunotherapy suppresses the type 2 responses through the induction of allergen-specific regulatory T/B cells and in-duces the production of allergen-specific IgG4. However, the effects of allergen immunotherapy on memory CD4+ T cells are unknown.Methods:Memory CD4+ T cells were isolated from peripheral blood mononuclear cells of the patients with Japanese cedar pollinosis (JCP) before and afterthe sublingual immunotherapy (SLIT) with Japanese cedar pollen extract. The patients after SLIT were divided into responder and non-responder based on the clinical symptom medication score. We comprehensively analyzed microarray data on gene expression of memory CD4+T cells. The mRNA expression of apoptosis-related genes (Fas, Caspase 3, Nuclear factor-kappa B p100 (NFκB p100) and Double PHD Fingers 2(DPF2)) in memory CD4+ T cells were also examined by Real-Time PCR. Results: The microarray analysis revealed that memory CD4+ T cellsfrom SLIT responder showed lower expression of DPF2, anti-apoptotic gene, compared with those from JCP patients and SLIT non-responder.The mRNA expressions of DPF2 and NFκB p100 which activate anti-apoptotic pathway, were significantly suppressed after the SLIT, whilethose of Fas and Caspase 3 which activate the apoptotic pathway did not change. Conclusion: SLIT with Japanese cedar pollen extract inducesthe apoptosis of memory CD4+ T cells by suppressing the mRNA expressions of DPF2 and NFκB p100. Apoptosis of memory CD4+ T cells maybe involved in the long-term clinical tolerance after the SLIT.

PE23-6 Involvement of type 1 regulatory T (Tr1) in clinical effectiveness of sublingual immunotherapy (SLIT)

Masaya Matsuda1), Tetsuya Terada2), Kazuyuki Kitatani1), Ryo Kawata2), Takeshi Nabe1) (Laboratory of Immunopharmacology, Faculty of Pharma-ceutical Sciences, Setsunan University, Japan1); Department of Otorhinolaryngology-Head & Neck Surgery, Osaka Medical College, Japan2))

Background: Allergen-specific sublingual immunotherapy (SLIT) is clinically effective for allergic diseases such as Japanese cedar pollinosis,whereas mechanisms of the effectiveness have not been fully elucidated. Regulatory T (Treg) cells are generally divided into two main groups:Foxp3+ Treg cells and Foxp3- type 1 regulatory T (Tr1) cells. More recently, it has become clear that the number of Foxp3+ Treg cells are in-creased by SLIT. However, it is unclear whether the number of Tr1 cells are increased by SLIT. The purpose of this study was to elucidatewhether Tr1 cells play roles in the effectiveness of SLIT. Methods: SLIT treatment was started in 2014 or 2015 in Japanese cedar pollinosis pa-tients, and had been continued until May 2019. In May 2017 and May 2019, peripheral blood mononuclear cells (PBMCs) were collected from thepatients, and analyzed by flow cytometer. In another experiment of mice, Tr1 cells were induced in vitro by the culture of splenocytes of ovalbu-min (OVA)-sensitized BALB/c mice with OVA and IL-21, IL-27 and TGF-β and adoptively transferred to OVA-induced asthmatic mice. Airwayhyperresponsiveness to methacholine was measured by forced oscillation technique. Results: (1) Visual analogue scale score, a parameter of clini-cal effects for nasal symptoms in 2019 was significantly improved in comparison with that in 2017. (2) The number of Tr1 cells (IL-10-producingFoxp3- CD4+ T cells) in PBMCs collected in 2019 were significantly larger than those in 2017. (3) When spleen cells isolated from the OVA-sensitized mice were cultured with OVA together with cytokines in vitro, Tr1 cells were efficiently proliferated. (4) The adoptive transfer of Tr1cells significantly suppressed the development of airway hyperresponsiveness, and increases in eosinophils and neutrophils in BAL fluid. (5) Thetransfer of Tr1 cells significantly suppressed the increase in IL-5 in BAL fluid. Conclusion: Tr1 cells could play roles in clinical effectiveness ofSLIT.

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PosterSession

PE23-7 Immunological responses during long-term sublingual immunotherapy with Japanese cedar droplet

Tomokazu Matsuoka1,2), Satoko Kobayashi3), Katsuyo Ohashi-Doi3), Kimihiro Okubo4), Keisuke Masuyama2,5) (Department of Otorhinolaryngology,Head & Neck Surgery, University of Yamanashi, Japan1); Allergy Center, University of Yamanashi Hospital, Japan2); Torii Pharmaceutical Co.,Ltd., Japan3); Department of Otolaryngology, Head and Neck Surgery, Nippon Medical School, Japan4); Department of Otolaryngology, Suwa Cen-tral Hospital, Japan5))

Background: Allergy immunotherapy (AIT) is the only disease modifying treatment for IgE-mediated allergy. Standardized Japanese cedar (JC)droplet has been developed for sublingual immunotherapy (SLIT) for Japanese cedar (JC) pollinosis. This study aims to investigate immunologicalresponse during long-term SLIT with standardized JC droplet.Methods: A total of 233 patients with JC pollen induced allergic rhinoconjunctivitiswere enrolled in this phase IV trial (JapicCTI-142585). Patients received daily sublingual administration of standardized JC pollen droplet (2,000JAU) for 33 months. Serum samples were collected over time. Total-IgE (t-IgE), JC specific-IgE (s-IgE), and JC specific-IgG4 (s-IgG4) were meas-ured by ImmunoCAP (Phadia, Thermo Fisher Diagnostics K.K.). Results: Change of t-IgE and s-IgE value was similar. After the start of treatmentwith JC pollen-droplet, s-IgE was immediately increased from baseline. The peak of increased s-IgE was detected at 12 weeks after treatment.Slightly increase of s-IgE with SLIT patients was detected after natural JC pollen exposure. During the SLIT-droplet treatment, s-IgE value wasgradually decreased and reached to same level of baseline at the end of treatment. S-IgG4 was significantly increased and peaked at 12 weeks andit maintained the same value during treatment. Ratio of s-IgE/s-IgG4 was increased and peaked 12 weeks, and then the ratio was decreased forend of treatment. Discussion: SLIT-drops treatment induced s-IgE and s-IgG4 production in serum. Type II response was a major type of im-mune response in initiate of SILT. Long-term SLIT elicits Immuno-deviation and may lead to immunological tolerance. Ratio of s-IgE/s-IgG4 maybe considered to have a potential marker for change in immunological response to allergen.

PE23-8 Significance of house dust mite components in the selection of specific immunotherapy

Gabija Biliute1), Asta Miskiniene2), Loreta Bagdonaite3), Jolita Norkuniene4), Violeta Kvedariene5,6) (Faculty of Medicine, Vilnius University, Lithu-ania1); UAB In novum, Lithuania2); Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University, Lithuania3); Vilnius Gediminas Techni-cal University, Lithuania4); Clinic of Chest diseases, Immunology and Allergology, Institute of Clinical Medicine, Vilnius University, Lithuania5); Vil-nius University Hospital Santaros Klinikos, Lithuania6))

Background: To evaluate the diagnostic relevance of home dust mite (HDM) allergen components before choosing specific immunotherapy.Methods: 179 patients with symptoms of allergic rhinitis and/or bronchial asthma were tested for specific IgE with ALEX (Allergen Explorer)macroarray at the laboratory“Invitro diagnostics”, Vilnius, Lithuania. 82 subjects were tested with ALEX1 and 97 subjects were tested withALEX2 macroarrays. HDM Dermatophagoides pteronyssinus (Der p) allergen components were analyzed. Patients were divided into two groups.The first group included polysensitized patients, while the second group included patients with only one allergen component sensitization. Re-sults: 179 patients with suspected allergies were investigated: 94 (52,51%) females and 85 (47,48%) males. The study group included 111 childrenunder 18 years of age, average age 6,5 years and 68 adults, average age 38 years. Sensitization to Der p allergens was found in 57 (31,84%) indi-viduals: 29 (50,88%) females and 28 (49,12%) males. Statistically there was no significant difference in sensitization to Der p between children andadults (p-value>0,05). In the first group 47 (82,46%) patients were polysensitized to Der p allergen components. The majority of patients were sen-sitized to Der p 1 (n=33; 57,89%) and Der p 2 (n=40; 70,18%) components. However, substantial amount of patients in addition were sensitized to anallergen components not commonly used in immunotherapy: Der p 23 (n=34; 59,65%), Der p 5 (n=15; 26,32%), Der p 7 (n=17; 29,82%), Der p 10 (n=6;10,53%). In the second group, 10 (17,54%) patients were sensitized to other Der p components: 4 (7,02%) patients were monosensitized to Der p 23,3 (5,26%) were monosensitized to Der p 10, 2 (3,51%) were monosensitized to Der p 5 and 1 (1,75%) patient was monosensitized to Der p 21. Conclu-sion: Our study shows the importance of molecular testing for choosing AIT for HDM allergic individuals. 10 (17.54%) Der p positive patientswere not sensitized to major D.pteronyssinus components Der p 1 and Der p 2 and showed sensitization profiles to less common molecular Der pallergens. Treatment of such patients with currently available AIT medication may prove to be ineffective.

PE23-9 Changes in specific immunoglobulin G4 levels during pediatric subcutaneous immunotherapy with Japanese cedar pollen

Mayumi Fujita, Shuntaro Tsumagari, Tetsuya Takamasu, Chisato Inuo (Department of Allergy, Kanagawa Children’s Medical Center, Japan)

Background: Levels of pollen-specific immunoglobulin G4 (IgG4) increase after pollen-based subcutaneous immunotherapy (SCIT), but the mecha-nisms mediating this increase remain obscure. This retrospective study evaluated the effects of the effective doses and frequencies of Japanesecedar pollen (JCP)-based SCIT on JCP-specific IgG4 levels.Method: Fifty-nine patients (male, 42; female, 17; age, median [range]: 9 [515] years) withJCP-induced allergic rhinitis received JCP-based SCIT for more than 2 years. The JCP-specific IgG4 levels were compared between the high- andlow-dose groups (maintenance dose >200 or 200 JAU, respectively) and the high- and low-frequency groups (injection frequency 10 and <10 timesper year, respectively). Results:Median JCP-specific IgE levels were 94.6 UA/mL in this study population. JCP-specific IgG4 levels increased sig-nificantly after 2-year SCIT (0.292 to 2.48 mgA/mL, P<0.05), were significantly elevated in the high-dose group than in the lose-dose group (me-dian: 5.150 and 3.045 mgA/mL, respectively, P<0.05), and did not significantly differ between the high- and low-frequency groups (median values:3.355 and 3.89 mgA/mL, respectively, P=0.47). Conclusion: JCP-based SCIT increased JCP-specific IgG4 levels for more than 2 years, and theseelevated levels were associated with SCIT dose concentration than with injection.

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PosterSession

PE23-10 Induction of Th1 CD4 T cells with peptide vaccine

Takumi Kumai1,2), Ryosuke Sato2), Toshihiro Nagato2), Yasuaki Harabuchi2) (Department of Innovative Head & Neck Cancer Research and Treat-ment (IHNCRT), Asahikawa Medical University, Japan1); Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University,Japan2))

The imbalance of Th1/Th2 subset is a hallmark of allergic disease. The subcutaneous and sublingual immunotherapy has improved the allergicsymptom. In addition to the induction of IgG4 neutralizing antibody and regulatory T cells, skewing CD4 helper T cells to Th1 subset might playrole in attenuating allergy. Because these treatments require several months to years to relieve the clinical symptoms, it is necessary to establishmore rapid and efficient method to induce antigen-specific Th1 cells. Here, we describe a peptide vaccination strategy capable of generating vastCD4 Th1 responses by combining synthetic peptides with toll-like receptor (TLR) ligands and costimulatory molecule agonists. Among TLRligands, TLR7 ligand gardiquimod capably induced peptide-specific Th1 cells. These results have practical implications in the design of effectiveactive immunotherapy.

PE23-11 Comparison of immunological effect of standardized and non-standardized extracts in subcutaneous immunotherapy for childrenwith house dust mite-induced perennial rhinitis

Shuntaro Tsumagari, Mayumi Fujita, Tetsuya Takamasu, Chisato Inuo (Department of Allergy, Kanagawa Chileren’s Medical Center, Japan)

Background: Non-standardized house dust (HD) extract has been used in subcutaneous immunotherapy (SCIT) for patients with perennial rhini-tis in Japan. Recently a new standardized house dust mite (HDM) extract has been available in SCIT. The purpose of the present study was tocompare the immunological efficacy of standardized and non-standardized extracts. Method: Ten patients (male 8; female 2; median age: 11.0;range 6-13 years) received SCIT more than three years for HDM-induced allergic rhinitis. The immunological evaluation involved a comparison ofthe HD group and the HDM group. Serum Dermatophagoides farinae (Der f)-specific Immunoglobilin (Ig) E antibody levels were compared beforeand after SCIT. Der f-specific IgG4 levels were evaluated after SCIT. Results: Five patients received HD extract and five received HDM extract.The Der f-specific IgE levels among both groups tended to increase (HD: 257 UA/mL to 313 UA/mL; P=0.188, HDM: 174 UA/mL to 247 UA/mL;P=0.063, respectively). There was no significant difference in Der f-specific IgG4 levels between the HD and HDM group (median: 2.53 and 2.39mg/mL, P=1.00), and there was no significant difference in Der f-specific IgE/IgG4 ratio between the two groups (P=1.00). Conclusion: The pre-sent result suggest that the SCITusing both non-standardized HD and standardized HDM extractinduces immunological change in children withhouse dust mite-induced perennial rhinitis.

PE23-12 The establishment of EXiLE test for house dust mite allergy

Katsuyo Ohashi-Doi1), Yuya Tanaka2), Ikuo Okafuji2), Satoru Tsuruta2), Saori Ohmae1) (Research Laboratory, Torii Pharmaceutical Co., Ltd, Japan1);Department of Pediatrics, The Kobe City Medical Center General Hospital, Japan2))

Background: Successful allergen immunotherapy (AIT) is associated with an increase in the production of allergen-specific IgG antibodies includ-ing IgG4 which may contribute to IgE-blocking factor (IgE-BF) activity. Recently, in vitro allergy test method was reported as EXiLE (IgEcrosslinking-induced luciferase expression) test using a luciferase-reporting humanized rat mast cell line. However, to understand immunomodula-tion effect after AIT, this functional assay has not been fully validated. Objective: This study is aimed to investigate effect of IgE-BFs induced byhouse dust mite (HDM)-AIT on EXiLE test. Method: HDM allergic rhinitis patients’ sera before- and after-AIT were used. EXiLE test was per-formed as previously reported (Allergol. Int, 2012). Briefly, RS-ATL8 cells were plated into the wells of a 96 well-plate and incubated with dilutedserum overnight. The cells were stimulated with allergen (HDM, 0.1-1000 ng/mL) without washing. Then, luciferase substrate was added to thecells, and chemiluminescence was measured. The data was expressed as luciferase expression (LE) levels which were represented as the fold in-crease compared with the allergen untreated conditions (baseline), and EC50 value was calculated by fitting a dose response curve. Results: Theoptimal incubation time was 3hr with HDM (0.1-1000 ng/mL). The LE levels showed significant correlation with the value of Der p specific-IgE (r2>0.95). EC50 of LE levels in sera after-AIT was shifted from that in sera before-AIT (p=0.01). Conclusion: EXiLE test was established for theHDM allergic rhinitis sera. This test can be utilized for immunomodulation effect induced by AIT.

222

PosterSession

PE23-13 Allergen stability and immunological reactivity following dissolution and co-Incubation of house dust mite and Japanese cedarpollen SLIT-Tablets

Katsuyo Ohashi-Doi, Hiroki Matsuhara, Takashi Yamamoto, Keisuke Suzuki, Hiroshi Nakazawa (Research Laboratory, Torii Pharmaceutical Co.,Ltd, Japan)

Background/Objective: Japanese allergic subjects are commonly sensitized to both house dust mite (HDM) and Japanese cedar pollen (JCP) andcombined treatment with SLIT tablets is desirable. However, mixing extracts of two non-homologous allergens may compromise allergen stabil-ity and affect the clinical outcome. Therefore, we investigated the stability of major allergens and total allergenic reactivity of HDM and JCPSLIT-tablets following dissolution and co-incubation in human saliva or artificial gastric juice. Methods: Two fast-dissolving freeze-dried SLIT-tablets (HDM or JCP) were used. SLIT-tablets were completely dissolved in assay butter (100 mM phosphate, pH6.8, 0.125% casein), a pool of hu-man saliva or artificial gastric juice (0.32% (w/v) pepsin, 0.03% M NaCl, 0.084 M HCl, pH=1.2). The SLIT-tablet solutions were mixed, co-incubatedat 37°C, or incubated separately. Major allergen concentrations (Der f 1, Der p 1, Der Gr.2 and Cry j 1) and total HDM and JCP allergenic reactivitywere measured by ELISA at t=0 min and t=10 min. Results: After incubation of the two SLIT-tablets in human saliva, no statistically significantdifferences in major allergen concentrations were detected compared to the control (t=0 vs. t=10). Likewise, no loss of allergenic reactivity of themixed SLIT-tablet solutions was seen after co-incubation in human saliva for 10 minutes at 37°C. In contrast, complete loss of allergenic reactivityand detectable major allergen concentrations occurred when the two SLIT-tablets were dissolved and incubated in artificial gastric juice. Conclu-sion: These results demonstrate that the total allergenic reactivity of both SLIT-tablets as well as the HDM or JCP major allergens measuredhere remain intact after dissolution and co-incubation in human saliva, supporting the possibility of a dual HDM and JCP SLIT-tablet administra-tion regimen if clinically indicated. The complete loss of allergenic reactivity after incubation in artificial gastric juice can furthermore be taken toindicate that the immunological activity of the allergen extracts contained in the two SLIT-tablets is likely to be lost or severely compromisedupon swallowing.

PE23-14 A role of basophil activation and antigen specific antibody in sublingual immunotherapy for seasonal allergic rhinitis

Yosuke Baba1), Kazuki Miyabayashi1,2), Shoji Ishida1,2), Takahiro Ebara1,2), Mayuki Kojima2), Hiromichi Yamada2), Toshiyuki Yoneyama2),Tomoaki Yokokura1,2), Susumu Yamazaki2), Asuka Honjo2), Eisuke Inage2), Takahiro Kudo2), Yoshikazu Ohtsuka2), Toshiaki Shimizu2) (Departmentof Pediatrics, Juntendo University Shizuoka Hospital, Japan1); Department of Pediatrics, Juntendo University School of Medicine, Japan2))

Background: Sublingual immunotherapy (SLIT) for seasonal allergic rhinitis (SAR) caused by cedar pollen is effective in children, but there arefew clinical studies that consider the immunological mechanisms in children. Purpose:We investigated nasal symptom scores, changes in antigen-specific antibodies, and basophil activation in peripheral blood to evalute the efficacy and immunological response to SLIT in children. Meth-ods: Patients with SAR who visited our hospital during the 2018/2019 and 2019/2020 seasons were included in the study. We included patientsyounger than 11 years old who were diagnosed with SAR and started SLIT. Symptom scores were observed and compared with symptoms fromone year earlier. The nasal symptom score (TNSS) was used for the symptom score. Blood tests were performed before treatment, 3 months aftertreatment and during the cedar dispersal season. We evaluated the immunological changes by the Immuno CAPⓇ assay (Thermo, Sweden) usingcedar crude antigen-specific IgE, IgA, and IgG4, and measured CD3-, CD203c+, and CRTH2+ cells as basophils from the patients’ peripheral bloodfor basophil activation, and the rate of CD203c activation by antigen stimulation was identified and examined. Results: Nineteen patients (male: fe-male=11/8) were included in the study. The median age was 8 years and 2 months (7 years and 0 months to 11 years and 10 months), and all pa-tients exhibited significant improvement in TNSS. Additionally, significant changes in specific antibodies were observed with treatment. In par-ticular, cedar-specific IgA levels increased 3 months after treatment. Discussion: The present study suggests that SLIT may induce early bloodIgA antibodies, which may involve the activation of basophils and thus induce immune tolerance.

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PosterSession

Poster Session 24Mechanisms of allergy

PE24-5 The flagellin allergen fusion protein rFlaA: Betv1 induces MyD88-, mTOR-, and MAPK-dependent immune metabolic activationof macrophages

Yen-Ju Lin, Stephan Scheurer, Garibald Papp, Anna Fiedler, Alexandra Goretzki, Sonja Wolfheimer, Stefan Vieths, Stefan Schülke (Molecular Al-lergology, Paul-Ehrlich-Institut, Germany)

Background: Recently, a conjugate of the TLR5-ligand flagellin A and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) has been shown to prevent birchpollen allergy in mice. The preventive effect was associated with a mTOR-dependent activation of myeloid dendritic cells (mDC) and secretion of IL-10. Ob-jective of the present study was to study the immune metabolic effect of recombinant (r) FlaA:Betv1 on bone marrow-derived macrophages (BMDM).Meth-ods: BMDM were differentiated from BALB/c, C57BL/6, TLR5-/-, or MyD88-/- mice, stimulated with rFlaA:Betv1, and analyzed for activation, cytokine se-cretion, and metabolic state. For mechanistic studies, C57BL/6 BMDM were pre-incubated with a mTOR or JNK-MAP kinase (MAPK) inhibitor and subse-quently analyzed for metabolic activation and cytokine secretion. In addition, BALB/c BMDM were co-cultured with CD4+ T cells (TC) from Bet v 1/Alumimmunized mice and checked the effect of rFlaA:Betv1 on Bet v 1-induced Th2 responses. Results: Treatment with rFlaA:Betv1 resulted in a MyD88-dependent IL-6 and IL-10 production, accompanied with an upregulation of TLR5-, CD40-, and CD69-surface expression. Metabolic analysis showed thatrFlaA:Betv1 induced a MyD88-dependent Warburg Effect. Different from mDC, BMDM stimulated with the mixture of rFlaA and rBet v 1 induced a TLR5-dependent metabolic activation. Pre-incubation of rFlaA:Betv1-stimulated C57BL/6 BMDM with either a mTOR- or JNK-inhibitor resulted in suppression ofmetabolic activation. Western blot analysis revealed stronger activation of MAPK-, NFKB-, and mTOR-signaling after rFlaA:Betv1-stimulation. In BMDM:CD4+ TC co-cultures, rFlaA:Betv1 significantly suppressed Bet v 1-induced IL-5 and IL-13 secretion while inducing IFN-γ production. Conclusion: FlaA:Betv1showed stronger immune modulating effects than the non-conjugated components. Stimulation of BMDM with rFlaA:Betv1 induces a MyD88-, MAPK-dependent cytokine secretion and activation of glucose metabolism. In BMDM mTOR is engaged in the glucose metabolism but likely not engaged in the IL-6- and IL-10 induction. Therefore, macrophages likely contribute to the immune modulating effects of rFlaA:Betv1 previously observed in vivo.

PE24-6 Detection of eosinophil ETosis in eosinophilic granulomatosis with polyangiitis (EGPA) by citrullinated histone H3 immunostain-ing

Mineyo Fukuchi1), Yosuke Kamide2), Shigeharu Ueki1), Yui Miyabe1), Chikako Furutani1), Yuki Moritoki1), Akiko Saga1), Tomoo Saga1),Masami Taniguchi2) (Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine,Japan1); Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan2))

Background: ETosis is an active process of cell death that mediates lytic degranulation and release of filamentous chromatin structures called ex-tracellular traps (ETs). In neutrophils, histone hypercitrullination is believed to play an essential role in the formation of ETs by relaxing chroma-tin structure. Histone citrullination in eosinophil ETosis (EETosis) and their occurrence in EGPA have not investigated.Methods: Isolated eosino-phils were induced EETosis, apoptosis or necrosis and assessed by transmission electron microscopy and immunostaining of citrullinated histoneH3 (CitH3). We also obtained 26 biopsy samples from EGPA patients and performed by H&E staining and immunostaining for CitH3. Results:Electron microscopy revealed that EETotic cells showed chromatolysis and plasma membrane disintegration, releasing net-like CitH3 stainedETs, although they were not observed in apoptotic and necrotic cells. H&E staining of affected tissue from EGPA patients showed chromatolyticeosinophils and free eosinophilic granules. Immunostaining of identical fields indicated that these chromatolytic eosinophils were stained with net-like CitH3. Although there were several nonspecifically-stained samples, eosinophil ETs were detected in 86% of the sample with sufficient stain-ing. Conclusion: Net-like CitH3-stained ETs was a hallmark of EETosis. Using H&E staining combined with CitH3 immunostaining, EETosis wasdetected in tissues from EGPA patients.

PE24-8 Sleep quality in patients with allergic rhinitis: the relationship between endogenous melatonin and nasal mucus cytokine levels

Aya Honma1,2), Viktoria Grammatopoulou3), Sofia Khan4), Mohammed Y Karim5), Masanobu Suzuki1), Yuji Nakamaru1), Akihiro Homma1),Vishnu S Sunkaraneni3), Debra J Skene2) (Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School ofMedicine, Hokkaido University, Japan1); Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, UK2); Department of ENT,Royal Surrey County Hospital, UK3); Department of Clinical and Experimental Epilepsy, National Hospital for Neurology and Neurosurgery, Uni-versity College London Hospital, UK4); Department of Immunology and Allergy, Royal Surrey County Hospital, UK5))

Background: Symptoms of allergic rhinitis (AR) get worse during the night and can influence sleep and daytime performance. For better under-standing of mechanisms underlying rhinitis-related sleep disturbances, we assessed sleep quality in AR patients and its association with mela-tonin rhythms and symptom severity. Methods: A total of 19 persistent AR patients and 18 healthy controls participated. Sleep quality, daytimesleepiness and chronotype were assessed by Pittsburgh Sleep Quality Index (PSQI), Epworth sleepiness scale (ESS), and Munich ChronotypeQuestionnaire. Rest/activity patterns were assessed using actigraphy. Symptom severity was assessed by mini Rhino-conjunctivitis Quality ofLife Questionnaire (RQLQ) and nasal mucus cytokine (IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, and TNF-α) levels. Diurnal rhythms in urinarymelatonin metabolite; 6-sulphatoxymelatonin and cortisol were analysed by radioimmunoassay. Results: In AR group, poor sleep quality was ob-served from PSQI global score (median 6.0, interquartile range 4.0-9.0, p<0.001 vs control; 3.0, 2.0-5.3) with 63.2% reporting poor sleep compared tocontrols (22.2% reporting poor sleep). Sleep latency was prolonged in AR group (median 18.5 min, interquartile range 14.1-32.8 min, p<0.05) com-pared to the control (7.8 min, 4.7-12.0 min). Night-time urinary 6-sulphatoxymelatonin levels correlated with PSQI global score (p<0.01, ρ=0.923),sleep duration, RQLQ score, and nasal mucus cytokine (TNF-α, IL-1β) levels (p<0.05, ρ=0.867, 0.718, 0.745, 0.733, respectively). Two-wayANOVA showed that urinary 6-sulphatoxymelatonin levels were significantly increased in AR group (F1, 191＝33.13, p<0.01) from 03.00-05.00 h (p<0.05, post-hoc Bonferroni’s test). Conclusions: Prolonged sleep latency associated with AR had a significant impact on patients’ sleep quality.Night-time 6-sulphatoxymelaton levels correlated with poor sleep quality and symptom severity. Increased night-time 6-sulphatoxymelatonin lev-els in AR group suggested that melatonin and its reported anti-inflammatory effects may be involved in the pathogenesis of AR.

224

PosterSession

PE24-9 Role of TRPC6 channel in eosinophil function

Akiko Sano, Hiroyuki Sano, Takashi Iwanaga, Yuji Tohda (Department of Respiratory Medicine and Allergology, Kindai University, School ofMedicine, Japan)

Background: Calcium signaling plays a key role in the regulation of many functional responses such as degranulation in airway inflammatorycells. The transient receptor potential canonical (TRPC) channels are known as subfamily of nonselective cation channels permeable to Ca2+, andthought to have a significant role in airway inflammation. Among the TRPC channels, TRPC6 expression has been demonstrated in humaneosinophils, however, the role of TRPC6 channel in regulating eosinophil function remains to be defined. The objective of this study was to exam-ine the role of TRPC6 channel in eosinophil Ca2+ signaling and degranulation.Methods: Eosinophils were isolated from human peripheral blood ofmildly atopic donors by a modification of the negative selection immunomagnetic separation technique. Detection of TRPC6 protein in humaneosinophils was performed using Western blot analysis. Eosinophil peroxidase (EPO) release was measured by enzyme assay. Intracellular Ca2+

concentration was analyzed by flow cytometry with Fluo3-AM loaded eosinophils. Results: TRPC 6 expression was detected in human eosino-phils by Western blotting. Application of FMLP caused a transient increase in intracellular Ca2+ concentration and was decreased when cellswere preincubated with TRPC6 channel inhibitor, SAR7334. FMLP-induced EPO release was also inhibited by SAR7334. Conclusion: Our datademonstrate that TRPC6 channel inhibitor attenuated FMLP-induced intracellular Ca2+ increase and eosinophil degranulation. These results sug-gest that TRPC6 channel-mediated calcium influx is likely to be involved in degranulation in human eosinophils.

PE24-10 Protein phosphatase enhances IgE class switch recombination, but to no IgG4

Kano Tanabe1), Seiji Inui2) (Department of Medical Technology, Kumamoto Health Science University, Japan1); Sugimura Hospital, Japan2))

Background: Type I allergy is mediated by IgE antibody, which is produced by B cells via class switch recombination (CSR). CD40 and IL-4 in-duce CSR to IgE and/or IgG4 in human B cells. However, the control mechanism is unclear how to select IgE or IgG4 CSR. Previously, we foundthat Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) and protein phosphatase 2A (PP2A) family molecules regulated IgE CSR via NF-κBalternative pathway. In this study, we show that PP2A family molecules enhance only IgE CSR, but not IgG4 CSR.Methods:We studied the acti-vation of protein phosphatase in a murine B cell line M12 cells by IL-4 and anti-CD40 Ab stimulation using a protein phosphatase assay. Further-more, we investigated whether the stimulation of a human B cell line Ramos cells by IL-4 and anti-CD40 Ab increased the epsilon germ line tran-script (εGLT) and γ4GLT which is an index of IgE CSR and IgG4 CSR respectively. The effect of CaMKII inhibitor (KN-93) and/or PP2A familyinhibitor (Okadaic acid) was evaluated by using real-time PCR of εGLT and γ4GLT. Results: Protein phosphatase activation was increased byIL-4 and anti-CD40 Ab stimulation corroborating the activation of PP2A family molecules by this stimulation. Next, we confirmed that IL-4 andCD40 stimulation increased both εGLT and γ4GLT expression in the Ramos cells. The addition of KN-93 and Okadaic acid decreased the εGLTexpression. However, increase of γ4GLT was inhibited by only KN-93, but not by Okadaic acid. Conclusion: These results suggest that CaMKIIis an enhancer of both the IgE CSR and IgG4 CSR. However, PP2A family molecules may enhance only IgE CSR, but not IgG4 CSR.

PE24-11 Induction of T2 responses in human skin dermal cells by epidermal keratinocyte homogenate

Shokei Murakami1,2), Kyoko Futamura1), Kenji Matsumoto1), Akio Matsuda1) (Department of Allergy and Clinical Immunology, National ResearchInstitute for Child Health and Development, Japan1); Department of Pediatrics, Toyama University School of Medicine, Japan2))

Background: Atopic dermatitis (AD) is characterized by pruritus, barrier dysfunction and type 2 inflammation of the skin. The“itch-scratch cy-cle”is a clinically well-known cause of exacerbation of AD, but the underlying molecular mechanisms remain largely unknown. We hypothesizedthat some substances released from epidermal keratinocytes damaged by scratching directly induce T2 responses, leading to exacerbation of AD.We tested this hypothesis in vitro.Methods: Confluently cultured normal human epidermal keratinocytes (NHEK) were thoroughly washed, soni-cated and centrifuged at 10,000 g . The solubilized supernatant was used as a human keratinocyte homogenate (HKH). HKH was added at a pro-tein concentration of 300 g/ml to three different types of cultured normal human skin tissue cells, i.e., NHEK, normal human dermal fibroblasts(NHDF) and human dermal blood microvascular endothelial cells (HMVEC-dBl), followed by incubation at 37C for 48 hours. qPCR and ELISAwere performed to measure, respectively, the mRNA expressions and protein concentrations of IL-6, IL-8, IL-33 and TSLP. Cytoplasmic and nu-clear fractions of NHDF were also prepared, and IL-33 protein expression was analyzed by Western blotting. Results: HKH induced no inflamma-tory cytokines in NHEK, whereas it significantly induced mRNA expression and protein production of IL-6 and IL-8 in HMVEC-dBl. Furthermore,it also significantly induced TSLP, IL-33, IL-6 and IL-8 mRNA expression in NHDF, and markedly induced nuclear IL-33 expression in NHDF.Conclusion: Our results indicate that the homogenate of epidermal keratinocytes acts as an alarmin on dermal cells to induce various inflamma-tory mediators, including type 2 cytokines, TSLP and IL-33. Accordingly, scratching may not only cause mechanical damage to skin: it may alsolead to induction of T2 responses in the dermal cells by mechanically-damaged epidermal keratinocytes.

225

PosterSession

PE24-12 Effects of β2-adrenergic agonists on house-dust mite-induced adhesion, superoxide anion generation, and degranulation of hu-man eosinophils

Yutaka Ueda1,2,3), Kazuyuki Nakagome1,3), Takehito Kobayashi1,3), Toru Noguchi1,3), Tomoyuki Soma1,3), Kenichi Tokuyama1,2), Makoto Nagata1,3) (Al-lergy Center, Saitama Medical University, Japan1); Department of Pediatrics, Saitama Medical University, Japan2); Department of RespiratoryMedicine, Saitama Medical University, Japan3))

Background: Allergic symptoms can be clinically aggravated by exposure to house dust even in subjects who are not sensitized to house dustmite (HDM)-allergen. We previously reported that Dermatophagoides farinae (Df), a representative HDM, or Der f 1, a major allergen of Df, inducethe effector functions of eosinophils, which may be an important mechanism for HDM-induced symptoms in non-sensitized patients. In a clinicalsetting, β2-adrenergic agonists, such as salbutamol and formoterol, are used during asthma exacerbation to release the airway obstruction. Sev-eral reports have suggested that some β2-adrenergic agonists have anti-inflammatory property. Objective: The objective of this study is to in-vestigate whether β2-adrenergic agonist could modify the Df- or Der f 1-induced activation of eosinophils. Methods: Blood eosinophils obtainedfrom healthy donors were pre-incubated with either formoterol (1 µM), salbutamol (1 µM), or buffer control and then stimulated with Df extract (1µg/ml) or Der f 1 (100 pg/ml). Eosinophil adhesion to intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays.Generation of superoxide anion (O2) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derivedneurotoxin (EDN) concentrations in cell media were measured by ELISA. Results: Formoterol, but not salbutamol, suppressed the Df- or Der f 1-induced eosinophil adhesion to ICAM-1. Furthermore, formoterol, but not salbutamol, suppressed Df-induced O2 generation or EDN release. Nei-ther formoterol nor salbutamol suppressed spontaneous eosinophil adhesion, O2 generation, or EDN release. Conclusion: These findings sug-gested that formoterol, but not salbutamol, suppressed Df- or Der f 1-induced eosinophil activation. Therefore, formoterol could potentially be ef-fective for the treatment of bronchial asthma via both bronchodilation and anti-inflammatory effect.

PE24-13 Functional food ingredients modulate mast cell signaling

Norimasa Tamehiro, Reiko Adachi, Kazunari Kondo (Department of Biochemistry, National Institute of Health Sciences, Japan)

Background: Mast cells have a key role in host defense against pathogens through the release of inflammatory mediators that also contributesthe pathogenesis of allergies and inflammatory diseases. Regulating the process for mast cell activation could be helpful to prevent allergic symp-toms.Methods:Mast cells express the high affinity IgE receptor (FcεRI) on cell surface, and antigen crosslinking the cell-bound IgE triggers therelease of histamine, prostaglandins and cytokines. We performed a bioactive screening of natural small molecules using EXiLE that employs lu-ciferase reporter system detecting Ca2+ influx which precedes the degranulation of mast cells. Humanized-mast cell line RS-ATL8 cells expressinghuman FceRI were passively sensitized with human sera and the natural compounds composed in our screening library were tested whether thestrength of the antibody cross-linking induced IgE signaling was affected by the treatment of these screening molecules. Results: Some of triter-penoides, flavonoids, cytochalasins, and phenylpropanoids extracted from food plants or medical herbs inhibited or activated the mast cell signal-ing upon IgE cross-linking and were mostly analogs of previously reported compounds. Conclusion: This study indicates that the natural smallmolecules in food can inhibit mast cell activation. There is the possibility that food ingredients intake is capable of inhibiting mast cell-mediated al-lergic reaction. Therefore, the functional ingredients contained in the foods and the herbs may offer health benefits for protect against food aller-gies.

PE24-14 Activated platelets can enhance airway inflammation and remodeling

Hoang Kim Tu Trinh1), Kieu-Minh Le1), Yoo Seob Shin2) (Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi MinhCity, Viet Nam1); Department of Allergy and Clinical Immunology, Ajou University Hospital, Republic of Korea2))

Background: Allergic asthma is characterized by chronic eosinophilic inflammation of the airways. The activation of inflammatory cells leads tothe release proinflammatory mediators, e.g interleukin (IL) 8, which can damage airway epithelial cells. Adenosine diphosphate (ADP), a mediatorreleased upon platelet activation, triggers degranulation of eosinophils through purinergic receptor P2Y12R. We suggested that ADP may contrib-ute to epithelial cell activation and disruption as well as the antagonists to the P2Y12R receptor could suppress the ADP-mediated epithelial activa-tion. Methods: mRNA from A549 cells were isolated and analyzed for expression of P2Y12R and β-actin as a reference gene using PCR. The re-lease of IL8 in cell-free supernatant was measured by ELISA. Expression of occludin and vimentin was evaluated by Western blot. P values wereanalyzed by one way ANOVA with Tukey post-hoc test. Results: P2Y12R was expressed on A549 cells at the mRNA level. Exposure to ADP, anagonist of P2Y12R, significantly induced activation of epithelial cells by releasing IL8 in a dose-dependent manner (P<0.05). ADP reduced the ex-pression of occluding (P<0.05), but there are no effects on vimentin expression. MRS 2395, an antagonist of P2Y12R, reduced significantly the re-lease of IL8 from A549 cells (P<0.05). Conclusions: Higher activation status of platelets may lead to damage of the epithelial layer and enhance air-way inflammation in asthma through P2Y12R.

226

PosterSession

PE24-17 Ephedra herb, Mao, inhibits allergen-induced mast cell degranulation by inducing IgE-FcεRI internalization

Yuka Nagata1), Hirokazu Ando2), Yohei Sasaki2), Ryo Suzuki1) (Laboratory of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Institute ofMedical, Pharmaceutical and Health Sciences, Kanazawa University, Japan1); Laboratory of Molecular Pharmacognosy, Faculty of PharmaceuticalSciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan2))

Background: Ephedra herb, known as Mao in Japan, is used as one of the ingredients of Japanese traditional prescription, called Kampo medicine,for treatment of allergic diseases. Mao exerts potent anti-allergic and anti-inflammatory effects, however, the underlying mechanisms remain elu-sive. In this study, we investigate the mechanisms of Mao on allergic inflammation using in vitro cultured mast cell (MC) and in vivo model of MC-dependent anaphylaxis.Method:Mao water extract was applied to bone marrow-derived mast cells (BMMCs) at final concentration of 100 µg/mlfor 30 min. The BMMCs were pre-sensitized with anti-DNP IgE and challenged by DNP-HSA. Degranulation responses (i.e. β-hexosaminidase re-lease) were compared with/without Mao treatment. The BMMCs were analyzed for both cell surface and intracellular IgE receptor (FcεRI)-bound IgE. Passive systemic anaphylaxis (PSA) model mice were subjected to intraperitoneal administration of Mao (50 mg/kg) for 6 hours fol-lowed by allergen challenge and the pathophysiological changes were evaluated. Results: The allergen, but not phorbol myristate acetate (PMA)and ionomycin, induced degranulation responses were attenuated in Mao-treated BMMCs. This data indicated that Mao inhibited IgE-dependentactivation of BMMCs. Mao-treated BMMCs exhibited significant reduction of cell surface expressions of IgE and its receptor FcεRI. Analysis oftheir subcellular localization by confocal laser scanning microscopy revealed that Mao treatment induced IgE-FcεRI internalization in BMMCswithout cell activation. Intraperitoneal administration of Mao to PSA mouse model resulted in the prevention of allergen-induced hypothermia.Further peritoneal MCs (PMCs) in the PSA mouse model showed significant reduction of cell surface expression of FcεRI after Mao administra-tion. These data indicated that Mao induced IgE-FcεRI internalization in the PMC and prevented activation of PMC upon antigen challenge.Conclusion: Mao induced IgE-FcεRI internalization in MCs, and may thereby inhibit the allergen-induced IgE-dependent degranulation. Thesefindings provide novel mechanism of Mao on MC functions and allergic responses. Our finding may serve as a new characteristic of Mao on aller-gic disease therapy.

PE24-18 Comparative evaluation of crude vis-a-vis purified allergen of Dermatophagoides farinae based on Indirect ELISA

Anita Leishangthem1), Venkatesh D P1), Nagendra Prasad K V2), Paranjothy K2), Lakshmi K2) (Department of Pharmaceutics, Acharya and BMReddy College of Pharmacy, India1); Bengaluru Allergy Centre, India2))

Background: Aim to purified the Dermatophagoides farinae allergen in a few simple steps for diagnostic purpose. Methods: Dermatophagoidesfarinae allergen was identified properly under microscope and defatted. The crude allergen extract was prepared by using the standard proce-dure which involves Homogenization of allergen using phosphate buffer and then centrifuged and supernatant was collected. The crude allergenwas compared to purified allergen. The purification step involves extraction of the allergen in phosphate buffer and the desired protein was pre-cipitate with 60% (w/v) ammonium sulphate at 4 degree celsius and the excess salt was removed by diafiltration using tangential flow filtrationwith 5 kDa cutoff membrane. Allergen was purified using chromatographic techniques by using Anion exchange resin. Column was equilibratedwith equilibration buffer (Phosphate Buffer, pH- 7.4, conductivity-3 mS). Extracted allergen was loaded on to the column followed by a post loadwash with equilibration buffer to remove weakly bound impurity. The allergen was eluted in gradient mode using phosphate buffer with highsalt. Eluted Allergen were collected in multiple fractions and analyzed for protein content, purity by SDS PAGE. Qualified fraction was character-ized further with indirect ELISA using patients serum. Results: The purified allergen (elution fraction) shows higher allergenic activity comparedto crude extract in indirect ELISA. The purified allergen was characterized by SDS-PAGE which showed significant band. Conclusion: The totalspecific allergenic activity was approximately 4 times higher (26%) in the purified preparation than in the crude extract against sensitive patients’serum from indirect ELISA.

227

PosterSession

Poster Session 25Microbiome and omics

PE25-1 Proteomic profiling of non-invasively collected skin surface lipid samples to characterize infant skin

Satoko Fukagawa, Kyoko Shima, Maeko Iwamura, Takayoshi Inoue, Junko Ishikawa, Noriyasu Ota, Takatoshi Murase (Biological Science Re-search, Kao Corporation, Japan)

Background: The objective of our study is to propose a novel, non-invasive method using an oil-blotting film for collection of proteins from theskin surface lipids (SSL) for evaluating the skin barrier abnormalities and immune status at the molecular level in infants. In this report, we com-pared the proteome patterns of healthy infants and those in infants with atopic dermatitis (AD), using total proteins from SSL. Methods: Sebumsamples from the facial skin were collected using an oil-blotting film. Proteins were extracted from a single film, followed by digestion into pep-tides, and were comprehensively analyzed using label-free quantitative proteomics with LC-MS/MS. Twenty-three healthy infants and 16 infantswith AD having lesions in the face and aged between 6 months to 5 years were recruited, and their profiles of SSL-Proteins were analyzed. Re-sults: To establish an optimal method for comprehensively analyzing the SSL-Proteins, the processes of protein extraction and tryptic digestion,and conditions of LC-MS/MS were investigated. In total, approximately 800 proteins were identified in the SSL samples from the face of the sub-jects. Among those 800 proteins, the proteins related to the epidermal development and the immune response were detected in SSL. Additionally,we found that the expression of proteins involved in the platelet degranulation and the negative regulation of endopeptidase activity were signifi-cantly elevated in infants with AD, compared to that in healthy infants. Conclusion: The analyses of proteins from SSL that can be easily collectedusing an oil-blotting film may be a non-invasive and useful method to characterize infant skin.

PE25-2 Bacterial flora in maternal feces, breast milk, breast skin, and 1-month breast milk and meconium

Yumiko Komine1), Yuki Fujimaki1), Yasuho Shoda1), Takehiko Soutome1), Gaku Harata2), Kenji Miyazawa2), Fang He2), Misa Watanabe1) (Departmentof Pediatrics, Toho University School of Medicine, Japan1); Takanashi Milk Products Co., Ltd, Japan2))

Purpose:We previously reported that administration of Lactobacillus GG (LGG) to pregnant women in the third trimester of pregnancy was effec-tive in controlling infant eczema until the age of 3 years. However, no direct effect on the intestinal flora of the offspring has been demonstrated,which suggests a mechanism through the placenta, breast milk, and so on. This study aimed to examine whether a relationship exists betweenbacterial floras in maternal feces, meconium, colostrum, breast skin at colostrum, and breast milk (1 month after birth) in pregnant women withLGG intake.Methods:Microbial composition in 37-week feces, meconium, colostrum, breast skin swab at colostrum, and breast milk at 1 month ofage were compared using a next-generation sequencer in 17 of the cases. Results: In the principal coordinate analysis, the floras in the 37-weekstool and mammary skin at colostrum were found at different coordinates, forming a unique mass of flora. Part of the colostrum formed its ownbacterial flora, but another part was mixed with meconium and bacterial flora in 1-month breast milk. Some of the bacterial flora in the meconium,breast milk, and colostrum were mixed. The diversity was high in the 37-week feces and colostrum. A significant difference in flora was found be-tween the colostrum and 1-month breast milk. When the occupancy rate of the bacteria was compared at the phylum level, the floral distributionsin the 37-week feces and meconium differed significantly. The microbial composition in colostrum, breast skin at colostrum, and 1-month breastmilk were similar, but these were different from that in meconium. The microbial composition in the 37-week feces, meconium, and colostrumwere significantly different at the order level, but those in breast skin at colostrum and 1-month breast milk were similar. Conclusion:Meconiumshowed a unique microflora, with non-vertical transmission as a possible mechanism. A comparison of microbial composition in stool samples atcolostrum and 1 month after birth is required.

PE25-3 Role of salivary microbiome in IL-10 production and efficacy of sublingual immunotherapy in allergic rhinitis

Aiko Oka1), Masanori Kidoguchi2,3), Shin Kariya4), Tazuko Fujiwara4), Atsushi Yuta5), Hiromi Miyashita5), Takaya Higaki4), Yukiko Ogawa5),Kengo Kanai6), Sei-ichiro Makihara7), Takenori Haruna8), Jun Kunisawa9), Emiko Noguchi3), Shigeharu Fujieda2), Kazunori Nishizaki4),Mitsuhiro Okano1,4) (Department of Otorhinolaryngology, International University of Health and Welfare Graduate School of Medicine, Japan1); De-partment of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui, Japan2); Department of Medical Genet-ics, Faculty of Medicine, University of Tsukuba, Japan3); Department of Otolaryngology-Head & Neck Surgery, Okayama University GraduateSchool of Medicine, Dentistry and Pharmaceutical Sciences, Japan4); Yuta Clinic, Japan5); Department Otorhinolaryngology-Head & Neck Surgery,Kagawa Prefectural Central Hospital, Japan6); Department Otorhinolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital, Japan7); Depart-ment Otorhinolaryngology, Himeji St Mary’s Hospital, Japan8); Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, andLaboratory of Gut Environmental System, National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN), Japan9))

Background: Levels of saliva-induced IL-10 by monocytic THP-1 cells is associated with clinical effectiveness of sublingual immunotherapy(SLIT) in allergic rhinitis. Since some salivary microbiome can induce IL-10 production, we sought to determine the association between the com-position ratio of salivary microbiome and the efficacy of SLIT in addition to the saliva-induced IL-10 production. Methods: One hundred and fourJapanese cedar pollinosis patients (age range, 1270 years; mean age, 33.8 years) were included and began SLIT. Prior to the start of SLIT, oral flu-ids were collected. Microbiome analysis of the saliva and measurement of in vitro IL-10 production from THP-1 cells induced by the saliva weredone. Results: Firmicutes, Bacteroidetes and Proteobacteria are three major phyla of salivary microbiome in Japanese subjects with Japanese ce-dar pollinosis. Composition ratio of Bacteroidetes phylum, especially Prevotella including P melaninogenica, and pallens species, significantly andpositively correlated with the level of saliva-induced IL-10 production. In addition, the composition ratio of Prevotella was significantly higher inasymptomatic patients as compared with symptomatic patients after SLIT. Conclusion: The results suggest that Bacteroidates especiallyPrevotella in saliva not only has a regulatory function to induce IL-10 production but also acts as a furnished oral adjuvant to enhance in the effec-tiveness of SLIT.

228

PosterSession

PE25-4 Identification of causative fungi in allergic bronchopulmonary mycosis by mycobiome analysis

Yoshiki Shiraishi1), Takashi Ishiguro2), Junko Suzuki3), Miyuki Wagatsuma4), Kirill Kryukov5), Kana Ohshinden1), Jun Tanaka1),Katsuyoshi Tomomatsu1), Tsuyoshi Oguma1), Katsuhiko Kamei6), Akira Hebisawa4), Tadashi Imanishi5), Koichiro Asano1) (Division of PulmonaryMedicine, Department of Medicine, Tokai University School of Medicine, Japan1); Department of Respiratory Medicine, Saitama Cardiovascularand Respiratory Center, Japan2); Department of Pulmonary Medicine, National Hospital Organization, Tokyo National Hospital, Japan3); ClinicalResearch Center, National Hospital Organization, Tokyo National Hospital, Japan4); Biomedical Informatics Laboratory, Department of MolecularLife Science, Tokai University School of Medicine, Japan5); Division of Clinical Research, Medical Mycology Research Center, Chiba University, Ja-pan6))

Rationale: It is difficult to identify the causative fungus in allergic bronchopulmonary mycosis (ABPM) due to low sensitivity of fungal cultureand serological tests. Therefore, we evaluated the usefulness of mycobiome analysis using next-generation sequencing (NGS). Methods: We col-lected formalin fixed paraffin embedded (FFPE) blocks of airway mucus plug with fungal hypha obtained from ABPM patients, and those withoutfungal hypha from asthmatic patients. DNA was extracted from FFPE samples, fungus-specific ITS1 region was amplified by PCR, and then thegene sequence was determined using Illumina MiSeq. Taxonomic classification of the sequence was performed using Genome Search Toolkit(GSTK; http://kirill-kryukov.com/study/tools/gstk/) and an in-house database, GenomeSync (http://genomesync.org). Results: In mucus culture,genus Aspergillus was detected in 22 cases of ABPM, and genus Penicillium in 1 case of ABPM. Aspergillus-specific IgG/precipitin was positivein 17 cases with ABPM, and IgE was detected in 26 cases. In contrast, genus of Aspergillus was not identified as the dominant fungi in any sam-ple on NGS analysis. Schizophyllum commune was detected as the major fungi in 63% of ABPM and 71% of asthma samples. Genus of Curvulariaand Trametes were identified as the dominant fungi in two samples, one with ABPM and the other with asthma. Conclusions:Mycobiome analy-sis can identify the causal fungi difficult with culture method or serological tests in ABPM and asthma.

PE25-5 Gut microbiome analysis for Japanese patients with multiple chemical sensitivity/idiopathic environmental intolerance

Kentaro Watai1), Kiyoshi Sekiya1), Masahira Hattori2), Yuichiro Kawasaki1), Norihiro Fujita1), Maki Iwata1), Kisako Nagayama1), Koichi Yano1),Yuto Nakamura1), Yuto Hamada1), Kai Ryu1), Hiroaki Hayashi1), Yosuke Kamide1), Yuma Fukutomi1), Masami Taniguchi1,3) (Clinical Research Centerfor Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan1); Graduate School of Advanced Science andEngineering, Waseda University, Japan2); Shonan Kamakura General Hospital, Center for Clinical and Translational Science, Japan3))

Background: Although the pathology of Multiple chemical sensitivity (MCS) is unknown, the involvement of central nervous system is reported.The association between the central nervous system and the intestine plays important role in many diseases. However, there is no report onanalysis of gut microbiome in MCS. Therefore, we aimed to identify gut microbiome variants associated with MCS using metagenomic sequenc-ing of fecal DNA. Methods: Prospectively, we recruited consecutive 30 patients with MCS and analyzed gut microbiomes of the patients withMCS comparing metagenomic data obtained from 104 age and sex-matched healthy controls (HC). Results: Akkermansia muciniphila and Faecali-bacterium prausnitzii were significantly different between MCS and HC in species level. No significant difference was observed between the twogroups in α and β diversity. Conclusion: Intestinal flora of the patients with MCS suggests more modest dysbiosis than that of the patients withinflammatory bowel diseases.

PE25-6 Does gut microbiota affect sensitization to inhaled allergens?

Atsushi Matsubara1), Ayami Nomura1), Junko Takahata1), Shigeyuki Nakaji2) (Department of Otorhinolaryngology, Hirosaki University GraduateSchool of Medicine, Japan1); Department of Social Medicine, Hirosaki University School of Medicine, Japan2))

Background: The importance of gut microbiota to human health has been the focus of many recent studies. It is reported that the intake Bifido-bacterium or Lactobacillus as probiotics reduces the symptoms of allergic rhinitis, atopic dermatitis, and bronchial asthma. However, few studieshave investigated how the gut microbiota is involved in sensitization to inhaled allergens. This study investigates the association between gut mi-crobiota composition and sensitization to major inhaled antigens in Japan.Material and Methods: The study comprised 1109 local residents whohad participated in the Iwaki Health Promotion Project in 2016. Blood samples were analyzed for levels of antigen-specific IgE against Japanesecedar pollen (JCP) and house dust (HD1). Fecal samples were analyzed for bacterial 16S rRNA using next generation sequencing. The percentcomposition of gut microbes was compared between patients sensitized and unsensitized group for JCP and HD1 to determine whether the rateof sensitization to inhaled antigens associates with specific bacterial orders composing the gut microbiota. Results: In participants aged 2049years, the percent composition of Bacteroidales was significantly higher among participants sensitized to JCP than in those unsensitized. The per-cent composition of Lactobacillales was significantly higher in participants unsensitized to HD group than in those sensitized to that antigen. Inaddition, participants with gut microbiota low in Bacteroidales and high in Bifidobacteriales or Lactobacillales has low sensitization rates to HDcompared with high in Bacteroidales and low in Bifidobacteriales or Lactobacillales. Conclusions: The presence of bacteria of order Lactobacil-lales, Bifidobacteriales, and Bacteroidale in the gut microbiota may affect sensitization to inhaled allergens.

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PosterSession

PE25-7 Identification of novel biomarkers for asthma reflecting lung eosinophilia by the non-targeted proteomics of serum exosomes

Hanako Yoshimura, Yoshito Takeda, Yuko Abe, Taro Koba, Yasuhiko Suga, Kiyoharu Fukushima, Shiroyama Takayuki, Shohei Koyama,Haruhiko Hirata, Kota Iwahori, Izumi Nagatomo, Atsushi Kumanogoh (Graduate School of Medicine, Osaka University, Japan)

Background: Asthma and chronic obstructive pulmonary disease (COPD) represent the two most common chronic respiratory diseases world-wide and both show significant heterogeneity and frequent overlap. Despite these complex and heterogeneous diseases, key biomarkers (BMs)are still lacking. While proteomics could be the most important omics among various omics, the current situation of proteomics in respiratory fieldis still the infancy. To overcome these problems, we focused on exosomes which contain both great deal of information from pathogenic cells andless noise proteins instead of serum by utilizing the state-of-art proteomics. Methods:We induced asthma model and emphysema model by oval-bumin and elastase, respectively. Serum exosomes were isolated by size exclusion chromatography, EV-Second. Isolated exosomes were con-firmed by transmission electron microscopy, immunoblot, and the Nanoparticle Tracking Analysis. To obtain novel BMs, we used non-label quan-titative proteomics of exosomes. Such BMs were further verified by immunoblotting and immunohistochemistry. Results: Using exosomes iso-lated from OVA-induced asthma model and elastase-induced emphysema model, we obtained 652 proteins by means of gel-free quantitative pro-teomics. EVs from controls, asthma and emphysema model were indistinguishable in number and size. Of note, 91 proteins were significantlyupregulated in the asthma model, and among them, 18 proteins were strongly correlated with eosinophil infiltration in the lung. On the otherhand, 69 proteins were upregulated in emphysema model, and 10 proteins were significantly correlated with alveolar enlargement. By IngenuityPathways Analysis, these up-regulated protein signature reflected their disease characteristics, respectively. Notably, while expression of 5 BMcandidates was significantly upregulated in asthma lung, 2 BM candidates were upregulated in emphysema lung. Of importance, significant corre-lation in expression was observed between exosome and diseased lung, indicating that protein profile from serum exosomes could reflect the pul-monary microenvironment. Finally, some of these biomarkers were further validated by immunoblotting in the independent set of mouse model.Conclusion: Our strategy to utilize exosome proteomics could provide novel BMs for future personalized medicine in asthma and COPD.

PE25-8 Surface bacterial flora in normal and dry mucosa

Ryosuke Miwa1), Masato Miwa2,3) (Minato Swan Dental Clinic, Japan1); Harimazaka Clinic, Japan2); Atopy Research Center, Juntendo University, Ja-pan3))

Background: Because of global warming, the dry syndrome is gathering attention. Dry skin has been recognized as a precursor stage of atopicdermatitis. The dry syndrome of mucosa includes dry mouth, dry eye and dry nose. To evaluate the bacterial population of the mucosal surface ofthe patients with dry syndrome, normal and dry nose subjects were performed conventional culture of nasal mucosa. Methods: Patients with na-sal symptom in outpatient clinic were classified as normal or dry nose clinically. Conventional bacterial culture was used bacterial identification.Results: 64 patients out of 98 complained dry nose. Bacterial cultures were positive in 73% of normal patients mainly Coagulase Negative Staphy-lococcus, Coryneform bacteria. Bacterial cultures were positive in 80% of dry nose patients mainly Coagulase Negative Staphylococcus, Staphylo-coccus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) were detected in only dry nose patients. Conclusion: Surface bacterial florabetween normal and dry nose showed different pattern. It remains unknown whether these differences are associated with nasal inflammation.Further study should be necessary also in patients with dry mouth and dry eye.

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Poster Session 26Other skin diseases 1

PE26-1 Effectiveness and safety of Omalizumab for chronic urticaria in Japanese children

Akihiko Terada (Terada Kid’s Allergy Clinic, Japan)

Aim: Anti-IgE monoclonal antibody (Omalizumab) is effective for allergic asthma. Recently it is also approved for the second line medicine ofchronic urticaria in Japanese children over 12 years old. Intractable chronic urticaria is quite a few patients in general pediatric clinic. Here we re-port five cases of intractable chronic urticaria. Material and Method: From December 2010 to December 2019, the type of urticaria was investi-gated from patient’s records. Diagnosis were acute urticaria at 56.6%, allergic reactions at 19.9%, chronic urticaria at 11.9% and physiological urti-caria at 10.1%. Ninety-five patients with chronic urticaria had been treated with common therapy such as antihistamine medicine and corticoster-oid. However, some patients have taken these medications for a long time. Among intractable chronic urticaria five patients above 12 years oldhave been treated with Omalizumab. Result: One patient had two course treatments, and other had one course treatment. Advanced events wereobserved in one patient with faint and worsened symptoms after first injection. However, a few weeks later he got successfully Omalizumab in-jection at three times monthly. It was not anaphylactic reaction by Omalizumab but vasovagal syncope. Other patients reduced symptoms andmedications without adverse reactions. Conclusion: Omalizumab therapy for chronic urticaria in children is well tolerated and effectiveness. It isvery important that patient should stay and be observed in the clinic for at least 30 min after injection of Omalizumab.

PE26-2 Allergic contact dermatitis to hair dye in 14-year-old male

Karolina Dumycz, Joanna Zieli ska, Beata Pyr ak, Dominika Ambro ej, Wojciech Feleszko (Department of Pediatric Respiratory Diseases and Al-lergy, Medical University of Warsaw, Poland)

Background: Para-phenylenediamine (PPD) is a well-known contact allergen that is mainly used as an ingredient in hair dyes and henna tattoos.The incidence of allergic contact dermatitis to PPD is increasing in pediatric patients. Case Report: A 14-year-old male presented to Clinic witherythematous lesions of the scalp and edema of the face. Six days before submission the boy had his hair dyed with pink colour without any reac-tion. Subsequently three days before submission the boy had his hair dyed with dark brown dye and a night after applying the substance erythe-matous lesions of the sculp and severe pruritus occurred. At the day before submission edema of the face and fever occurred. The boy hadshaved his hair and applied mometasone on the scalp but without any improvement. On physical examination at the admission to the hospital thepatient had erythematous papular lesions on the scalp, edema of the forehead and eyelids. Laboratory examination showed slight increase in cre-atinine level (0.9 mg/dl). Patient received oral cetirizine due to pruritus and hydrocortisone cream on erythematous lesions. On the next day swel-ling was more visible therefore patient received methylprednisolone every 8 hour for a one day. After a course of intravenous GCS edema anderythema significantly improved. Patient was discharged on oral bilastine for 7 days. The follow-up visit 7 weeks after the initial presentationshowed resolution of erythematous and popular lesions as well as edema. The standard patch test was performed and showed positive result forpara-phenylenediamine PPD (erythema and infiltration). Conclusions: PPD is a component of henna tattoos and hair dyes causing most commonlytype IV delayed hypersensitivity reactions. ACD develops in 7-10 days of the first contact with PPD. Reports on ACD show high sensitization ratein children to PPD (even 16% of suspected ACD) therefore application of henna tattoos and hair dyes in such population should be avoided.

PE26-6 Association between chronic spontaneous urticaria and sleep-disordered breathing

Kisako Nagayama1), Kiyoshi Sekiya1), Kentaro Watai1), Norihiro Fujita1), Maki Iwata1), Koichi Yano1), Yuki Hashimoto2), Yuto Nakamura1),Yuto Hamada1), Atsushi Miyake2), Kai Ryu1), Hiroaki Hayashi1), Hanako Ohmatsu2), Yosuke Kamide1), Yuma Fukutomi1), Masami Taniguchi3) (Clini-cal Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Japan1); Department of Derma-tology, National Hospital Organization Sagamihara National Hospital, Japan2); Shonan Kamakura General Hospital Center for Immunology and Al-lergology, Japan3))

Background: Chronic spontaneous urticaria (CSU) is a common disease caused by antigen-independent mast cell inflammation. Sleep-disorderedbreathing (SDB) contributes to various diseases by causing chronic inflammation. In our daily practice, we encountered a patient who showed im-provement in CSU following treatment for SDB. However, little is known about the association between CSU and SDB. Therefore, we conductedthis study to clarify this association. Methods: We studied consecutive patients with CSU who visited the Sagamihara National Hospital allergydepartment or dermatology department between April 1st and October 31st, 2018. Among them, an apnomonitor test (WatchPATⓇ, Philips, Inc.)was performed in those who consented to participate in this study. CSU was evaluated based on the Urticaria Activity Score 7 (UAS7), and SDBwas evaluated based on the peripheral arterial tone Apnea Hypopnea index (pAHI) derived from apnomonitor findings; the correlation betweenthe UAS7 and pAHI was then examined. Results: Consent was obtained from 37 of 45 patients, with 19 in the urticaria symptom-free-to-mild CSUgroup (UAS7≦15) and 18 in the moderate-to-severe CSU group (UAS7≧16). In the latter group, the pAHI and body mass index (BMI) were sig-nificantly higher than in the urticaria-free-to-mild CSU group (BMI＝21.0 vs. 27.3 kg/m2, p＝0.02; pAHI＝17.5 vs. 4.2, p<0.01). There was no signifi-cant difference between the two groups regarding the use of hypnotic drugs or doublets or quantitas duplexes with antihistamine drugs. In logis-tic analysis, the moderate-to-severe CSU group was significantly associated with moderate-to-severe SDB (pAHI≧15) when compared with theurticaria-free-to-mild CSU group, regardless of sex or BMI [odds ratio (OR) adjusted for sex＝29.6, p<0.05; OR adjusted for BMI＝21.7, p<0.05].Conclusion: SDB correlates with CSU independent of BMI and the use of doublets or quantitas duplexes with antihistamine drugs.

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PosterSession

PE26-7 Chinese doctors’ understanding of hereditary angioedema and the unmet needs in diagnosis and treatment: a qualitative study

N Zhao, Zhong Yuyan (Medical Affairs, Takeda (China) International Trade Co., Ltd., China)

Background: Hereditary angioedema (HAE) is a rare genetic disease with a worldwide prevalence of ～1:50,000, with an estimated 28,000 HAEpatients in China. The current qualitative study evaluated Chinese physicians’ perspectives on HAE, including unmet needs in diagnosis andtreatment. Methods: In-depth interviews with multidisciplinary physicians in China (eg, allergists, dermatologists, gastroenterologists, pediatri-cians) were conducted June through October, 2019. Results were analyzed using Colaizzi’s method (thematic analysis). Selection criteria werebased on the position physicians held in the Chinese Medical Association and the Chinese Medical Doctor Association, as well as authorship ofHAE-related literature. Results: A total of 16 physicians were interviewed. Findings showed widely varying knowledge levels. Four of 16 physi-cians (25%) were allergists and had a clear understanding of HAE diagnosis and treatment, whereas 12 of 16 physicians (75%) from other disci-plines were unfamiliar with HAE epidemiology or manifestations, and most had become aware of this disease within the previous 2-3 years. Find-ings showed that various medical disciplines are involved in HAE diagnosis and treatment, with a high rate of misdiagnosis within each specialty;only 50% (8/16) of physicians were aware that measurement of CI-INH levels/function is the gold standard for HAE diagnosis. Due to multiple ob-stacles, the C1-INH assay is currently only available at 3 hospitals in China. Regarding treatment, findings showed that allergists often use freshfrozen plasma to treat acute HAE attacks. For prophylactic therapy, 25% (4/16) of physicians (all allergists) indicated that they would select an-drogens, whereas 38% (6/16) of physicians from other disciplines would select antihistamines for attack prevention, and 38% (6/16) of physicianswould not use prophylactic therapy but rather, would instruct patients to avoid triggering factors. Additional challenges include a poor under-standing of newer C1-INH replacement therapies and the fact that only patients with recurrent and intractable HAE can be referred to more spe-cialized medical institutions or provided with expert consultation. Conclusion: Findings underscore the need to improve Chinese physicians’awareness of HAE and recommended diagnosis and treatment strategies.

PE26-8 Lipid mediator profiles of chronic spontaneous urticaria and atopic dermatitis

Maho Tagui1,2,4), Shota Toyoshima2,3,4), Yoshimi Miki5), Takahiro Endo1,2,4), Mana Ito1,2,4), Yusuke Niwa1,2,4), Yoshitaka Taketomi5,6),Koremasa Hayama1,2,4), Tomomi Sakamoto2,3,4), Makoto Murakami5,6), Tadashi Terui1,2,4), Yoshimichi Okayama2,3,4) (Department of Dermatology, Ni-hon University School of Medicine, Japan1); Allergy and Immunology Research Project Team, Research Institute of Medical Science, Nihon Uni-versity School of Medicine, Japan2); Center for Institutional Reseach and Medical Education, Nihon University School of Medicine, Japan3); Centerfor Allergy, Nihon University Shool of Medicine, Japan4); Laboratory of Microenvironmental Metabolic Health Sciences, Center for Disease Biol-ogy and Integrative Medicine, The University of Tokyo, Japan5); Department of Cellular Signaling, Faculty of Medicine, The University of Tokyo,Japan6))

Background: Lipid metabolites are involved in the skin homeostasis and the development of allergic diseases. Chronic spontaneous urticaria(CSU) is characterized by the appearance of erythema and wheal, lasting longer than six weeks. The trigger of CSU has been debatable. Atopicdermatitis (AD) is a disease mainly involving eczema with pruritus that repeats remission and exacerbation. The clinical symptoms of these skininflammatory diseases are similar, but the pathogenesis is different. The profiles of lipid metabolites of CSU and AD are not addressed. Objective:Our study purposes are to investigate the profiles of lipid metabolites in CSU and AD and to identify lipid metabolites contributing to the patho-genesis of CSU and AD. Methods:We collected plasma samples from forty-three CSU patients, twenty-two healthy normal controls (NC), and fif-teen AD patients. Lipid metabolites were analyzed using liquid chromatography-tandem mass spectrometry. Results: In arachidonic acid (AA)metabolites, we observed increase of the inflammatory mediator, LTE4 and reduction of the anti-inflammatory mediators, such as 15-deoxy PGJ2,LXA4 and LXB4, and the inflammatory mediator LTB4 in plasma from patients with CSU. Concentration of 8-HEPE, one of Eicosapentaenoic acid(EPA) metabolites, was significantly correlated with the severity of CSU. In AD, the AA metabolites, concentration of 15deoxyPGJ2, LXA4, LXB4

and LTB4 significantly decreased, but almost all lipid metabolites in patients with AD significantly decreased compared with those in NC. Manylipids in EPA and Docosahexaenoic acid (DHA) metabolites in patients with AD were also significantly decreased. Conclusion: Our results sug-gest that both increase in inflammatory metabolites and decrease in anti-inflammatory metabolites were involved in the pathogenesis of CSU andthat decrease in lipid metabolites was involved in pathogenesis of AD. Also, 8-HEPE concentration may be the biomarker for the severity of CSU.

PE26-9 Chronic spontaneous urticaria and thyroid disease in the elderly

Teresa Garriga-Baraut1,2), Carlos Hernández2), Andreu Garrigós2) (Department of Pneumology, Allergy and Cystic Fibrosis, Pediatric Allergy Unit,Vall d’Hebron University Hospital, Spain1); Centre Sociosanitari Putget Dolors Aleu, Generalitat de Catalunya, Spain2))

Background: Chronic spontaneous urticaria (CSU) is a common disorder characterised by the appearance of hives on a continuous or frequentlyrecurrent basis for more than six weeks. In most cases the aetiology is unknown, but in some cases thyroid disease has been associated with CSUin adults. However, in an extense review of the literature, few cases have been described in the elderly.Methods:We describe five elder patientswith CSU and thyroid disease. Each patient underwent complete clinical history and physical examination. The work up for CSU included levelsof serum complement, free thyroxine (T4), thyroid stimulating hormone/thyrotropin (TSH), antinuclear antibodies (ANA), antithyroid peroxidase(anti-TPO) antibodies and anti-thyroglobulin (anti-TG) antibodies. Results: We describe 5 patients (4 women and 1 man) with a mean age of 78year-old (range 74-82). All of them presented with the clinical feature and history of CSU and three patients had also recurrent facial angioedema.All of them had biochemical evidence of low plasma T4 and raised plasma TSH. Moreover, four patients had positive anti-TPO antibodies and/oranti-TG antibodies. ANA were positive in two patients. Levels of serum complement were normal in all cases. Three of these hypothyroid pa-tients treated with thyroxine had a complete remission of the urticaria and angioedema and the other two presented partial clinical improvement.Conclusions:We suggest that a search for hypothyroidism in the elderly should be carried out in elderly patients with CSU. This finding couldimply that elderly patients with thyroid disease could benefit of specifically directed therapy with thyroxine to improve CSU symptoms.

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PE26-11 Efficacy and safety of Ligelizumab for CSU in Japanese patients: subgroup analysis of phase 2b study

Michihiro Hide1), Atsushi Fukunaga2), Mami Murakami3), Eva Hua4), Thomas Severin5), Reinhold Janocha5), Atsuyuki Igarashi6) (Department of Der-matology, Institute of Biomedical and Health Sciences, Hiroshima University, Japan1); Department of Dermatology, Kobe University, Japan2); No-vartis Pharma K.K., Japan3); Shanghai Novartis Trading Ltd., China4); Novartis Pharma AG, Switzerland5); NTT Medical Center, Japan6))

Background: Ligelizumab is a next generation humanised monoclonal anti-IgE antibody which is binding with higher affinity to IgE than omali-zumab. Previously, the phase 2b dose-finding study demonstrated a dose-response relationship of ligelizumab in patients with moderate-to-severechronic spontaneous urticaria (CSU) with regard to complete hives response at week 12. In addition, more patients treated with ligelizumab 72 mgand 240 mg achieved HSS=0 and had a similar safety profile compared with omalizumab 300 mg. Here, we report the analysis of the Japanese sub-population from the phase 2b study. Methods: Japanese patients (N=36) with moderate-to-severe CSU (Urticaria Activity Score [UAS7] 16 andHives Severity Score [HSS7] 8) who were inadequately controlled with approved doses of H1-antihistamines (H1AH) were randomized to receivesubcutaneous ligelizumab 24 mg, 72 mg or 240 mg, omalizumab 300 mg, or placebo every 4 weeks over 20 weeks. Efficacy and safety were as-sessed primarily based on complete response in hives (HSS7=0), itch (Itch Severity Score [ISS7]=0) and urticaria activity (UAS7=0) at Week 12,and incidence of adverse events (AEs), respectively. Results: The median age of patients in this subgroup analysis was 42 years. HSS7=0 responserates at Week 12 were 37.5% (3/8), and 33.3% (3/9) for ligelizumab 72 mg, 240 mg respectively vs. 14.3% (1/7) for omalizumab 300 mg, 0% (0/4) forplacebo. ISS7=0 response rates at Week 12 were 25.0% (2/8), and 33.3% (3/9) for ligelizumab 72 mg, 240 mg respectively vs. 14.3% (1/7) for omali-zumab 300 mg, 0% (0/4) for placebo. UAS7=0 response rates at Week 12 were 25.0% (2/8), and 33.3% (3/9) for ligelizumab 72 mg and 240 mg re-spectively vs. 14.3% (1/7) for omalizumab 300 mg, 0% (0/4) for placebo. The safety profile of ligelizumab was comparable with that of omalizumab.Conclusion:While the number of patients in each group is limited, the safety profile of ligelizumab (N=21) was similar to omalizumab (N=7) in H1AH-refractory Japanese patients with CSU and more patients treated with ligelizumab achieved endpoints (HSS7=0, ISS7=0, UAS7=0).

PE26-12 Immune status of pregnant women with chronic urticaria

Oksana Gizinger1), Victor Radzinsky2), Elena Levkova1), Anna Khisamova1) (Immunology and Allergology, Peoples’ Friendship University of Russia,Russian Federation1); Obstetrics and Gynecology, Peoples’ Friendship University of Russia, Russian Federation2))

Urticaria is a polyetiological disease. Often, urticaria is accompanied by colonization of the surface of the skin of S. aureus, which worsens the con-dition of the woman. Established the leading role of the state of colonization of the skin microbiota in the clinical course of urticaria, with chroniccourse of the disease with severe severity according to the UAS-7 index, an increased colonization of the conditionally pathogenic Staphylococcusspp. microflora is noted, exceeding 3.79 - 5.91 times in comparison with indicators of healthy individuals. The aim of this study was improving themethods of diagnosis of urticaria, considering the immunological and microbiological parameters of the organism.122 pregnant women with urti-caria (PW-U) aged 24 to 39 years, the gestational age is 34,5±2,5 weeks and 45 pregnant women without urticaria (PW) of the concentration of IL-10, IL-4, IL-6, IL-2, IL-8, IgE and IFN-γ in the blood serum by ELISA method were determined. The number of CD3+, CD4+, CD4+CD25 + T-lymphocytes, CD19+, CD19+ CD23+ B-lymphocytes as well as CD203c+, CD203c + CD63 +, CD203c + basophils were assayed. The study foundthat the absolute level of CD3+ T-lymphocytes and CD19+ B-lymphocytes in urticaria women was statistically significantly lower than in PW (p<0.05). The relative and absolute levels of CD19+ CD23+ B-lymphocytes, CD203c+ CD63+ basophiles, significantly higher in PW-U (p<0.01). Thelevel of this indicator, as well as the level of CD203c basophils in PW-U was increased (p<0.05). No difference in the number of CD4+ CD25+ lym-phocytes have been determined in both groups. Activation of the cytokine status was established characterized by increased production of IL-4,IL -10, and pro-inflammatory IL-6, IL -8, regulatory cytokines IL-2. Here was high correlation between cytokine production and increased level ofS. aureus (often recorded in PW-U) and this may contribute to the colonization of the microbiota S. aureus and causing the development of bacte-rial sensitization in pregnancy. Affiliation 5-100 Peoples’ Friendship University of Russia, Moscow, Russian Federation

PE26-13 Immune status of pregnant women with acute urticaria

Oksana Gizinger1), Victor Radzinsky3), Natalya Mamylina2), Elena Levkova1) (Immunology and Allergology, Microbiology and Virology Peoples’Friendship University of Russia, Russian Federation1); South Ural State Humanitarian Pedagogical University, Russian Federation2); Obstetricsand Gynecology, Peoples’ Friendship University of Russia, Russian Federation3))

A significant increase in allergic dermatoses was noted in the structure of general allergopathology in pregnant women and among them up to50% is acute urticaria. The role of α-defensins HNP-1-3, IL-1β, -6, TNF-α, IL-4, -17, -8, -2 in blood serum in the implementation of the inflamma-tory response is not well established.47 pregnant women with chronic idiopathic urticaria aged 24.0±4.50 years were observed. The gestationalage -35.5±1.5 weeks. Blood sera was assayed for IL-1β, -6, TNF-α, IL-4, -17, -8, α-defensins, HNP-1-3, anaphylotoxins C3a, C5a by ELISA method.The expression of receptors for cytokines IL 2, -4, -8, -10 on the surface of peripheral blood lymphocytes was performed by flow cytometry. Inpregnant women with acute urticaria, the concentration of TNF-α increased by 56%, IL-1β - by 45%, IL-6 by 39%, IL-4 by 12% compared withthe control. Reliable results were not obtained by changing the content of IL-17. Against the background of an episode of acute urticaria in preg-nant women, a significant increase in IL-2 receptor expression was noted due to the CD122 subunit - 18.24±0.39%, 4.23±0,67% for IL 4, 12,6%; toIL 8 -19.78±0.37%, decreased expression of the receptor for IL 10 -18.21±0.45%. 88.7% of women with acute urticaria demobstrated a 29% in-crease in IL-10. Here was a direct correlation between IL-1β and IL-10, IL-4 and IL-1β. C3a increased by 25%, C5a by 15%, compared with thevalues in the control. HNP-1-3 was 350±26.7 pg/ml. in control. In pregnant women with an episode of acute urticaria, an increase in serum levelsof IL-1β, --4, -10, -6 TNF-α, α-defensins, HNP-1-3 was revealed. The results indicate a systemic inflammatory reaction, reflect the inclusion in theinflammatory process of the mechanisms of suppression of the overproduction of pro-inflammatory cytokines. The results obtained allow us totalk about solving the need for delivery in women with acute urticaria and a gestation period of 35.5±1.5 weeks.

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Poster Session 27Other skin diseases 2

PE27-1 Periorbital angioedema with acquired idiopathic generalized anhidrosis (AIGA) associated with sweat allergy: a case report

Mari Kishibe1), Yuki Kobayashi1), Shin Iinuma1), Michihiro Hide2), Akemi Ishida-Yamamoto1) (Department of Dermatology, Asahikawa Medical Uni-versity, Japan1); Department of Dermatology, Institute of Biomedical & Health Sciences, Hiroshima University, Japan2))

Cholinergic urticaria with periorbital angioedema has been reported in the associated with sweat allergy. It commonly affects young females witha high frequency of allergic diseases such as atopic dermatitis. AIGA is often accompanied by cholinergic urticaria mostly in young male patients.There is no report of sweat allergy-associated periorbital angioedema in combination with AIGA. Herein, we report a female patient with perior-bital edema and AIGA being resistant to treatment. A 22-year-old Japanese woman referred to our hospital because of repeated periorbital edemawith feeling sick. The symptoms were induced by bathing, excising, and outdoor activity on a hot day, which impaired her quality of life (QOL).The patient also had suffered from mild atopic dermatitis and cholinergic urticaria. She has no family history of similar conditions. Laboratorytests revealed no hypocomplementemia and normal C1-inhibitor. AlaSTAT assay revealed elevated anti- Malassezia IgE. Histamine-release testsusing patient’s basophils were positive for purified sweat antigens and Malassezia species, suggestive of sweat allergy. Modified starch-iodinetechnique detected anhidrosis in almost the entire body. The patient was diagnosed with periorbital angioedema, probably induced by sweat al-lergy, accompanied by AIGA. Rupatadine, lafutidine, montelukast sodium, and cyclosporine were administered to control angioedema. Moreover,corticosteroid pulse therapy (1000 mg of methylprednisolone for three days) was given three times to improve AIGA. The symptoms were allevi-ated, and the patient could take a bath for sweat training. Sweat allergy can cause periorbital angioedema. AIGA complicated by sweat allergy-associated angioedema made treatment more difficult. Sweat training in controlling symptoms of angioedema might be effective inducing toler-ance for the patient’s sweat as well as improving AIGA.

PE27-2 Gleich syndrome: a case report

Natalhie Acuña-Ortega, Maria Del Carmen Zarate Hernandez, Sandra N González-Díaz, Cindy E De Lira Quezada, Ligia L Carrasco-Díaz,Rodrigo A De la Cruz-Cruz (Regional Center of Allergy and Clinical Immunology, University Hospital Dr José Eleuterio González, Mexico)

Introduction: Gleich syndrome (GS) is a rare disease of unknown etiology that was first described in 1984 and since its description fewer than 50cases have been reported. It is characterized by recurrent episodes of urticaria, fever, angioedema, weight gain, and dramatic eosinophilia that oc-cur at 3-4-week intervals and resolve without therapy. Case Presentation: We report the case of a 42-year-old male who at 13 years old beganwith recurrent episodes of spontaneous urticaria and angioedema. When he was 40 years old, persistent eosinophilia was found in serial completeblood counts and was diagnosed with hypereosinophilic syndrome (HES). He was treated empirically with albendazole with no response. Serialstool parasite tests, serologies for rheumatoid factor, neutrophil cytoplasmic antibodies, antinuclear antibodies, tryptase, vitamin B12 levels, liverand kidney profile, urine analysis, skin allergy tests were all reported normal. A bone marrow aspiration showed no evidence of neoplastic infiltra-tion, a skin biopsy reported lymphocyte infiltrate, few neutrophils and some eosinophils in the dermis. We found high IgG at 1824mg/dl, and IgMat 734.8mg/dl and a normal electrophoresis study. He was treated with 480 mg/day of fexofendine, 5mg/day of prednisone and 500 mg/day of hy-droxyrea with partial response. Possible causes of HES in addition to eosinophil infiltration into vital organs were ruled out, and due to the clinicalcharacteristics he was diagnosed with Gleich syndrome. Discussion: GS is characterized by elevations of serum interleukin 5 (IL-5), increasedeosinophils, and increased numbers of activated T cells, associated frequently with increased serum IgM levels. Fever is likely to occur, and an-gioedema episodes tend to be mild. Patients commonly respond well to glucocorticoids due to their suppressive action on eosinophils proliferationand T-cell cytokine production, although if a T-cell clonal population is present, the risk of relapse is high and will need long-term treatment. Allpatients must have a diagnostic workup (T-cell phenotyping) to identify patients with underlying hypereosinophilic syndrome. Another treatmentthat has been reported to show efficacy is mepolizumab.

PE27-3 Expression of IL-27 and IFN-gamma in cutaneous mastocytosis

Tomonobu Ito, Tatsuo Maeda, Chizu Egusa, Takafumi Numata, Kazutoshi Harada, Ryoji Tsuboi (Department of Dermatology, Tokyo MedicalUniversity Hospital, Japan)

Background: The pathophysiology of cutaneous mastocytosis (CM) is not yet completely understood. To elucidate its pathogenesis, the expres-sion of cytokines and chemokines was analyzed by immunohistological staining. Methods: Skin specimens from ten patients (eight patients withmaculopaular cutaneous mastocytosis and two patients with mastocytoma) were stained with antibodies against IL-27, IL-27RA, IFN-gamma,CXCL10, CXCR3, and mast cell tryptase. Laser scanning confocal microscope images were obtained for analysis. Results: IFN-gamma, CXCL10,and CXCR3 were slightly expressed, and IL-27 and IL-27RA were not expressed at all in the mast cells of normal skin. However, IL-27, IL-27RA,IFN-gamma, CXCL10, and CXCR3 were highly expressed in all the CM patients. Conclusion: IL-27/IFN- gamma and CXCL10/CXCR3 were ex-pressed on the mast cells in CM, and aggregations of mast cells, which may have been caused by CXCL10, were observed in the lesions. The IL-27- CXCL10/CXCR3 axis pathway may help to elucidate the etiology of CM.

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PE27-4 The modern mass allergy is a syndrome of Demodectic Acariasis

Rakhima Zhaxylykova (Center of Traditional and Nontraditional Medicine, Kazakhstan)

Background: Currently, in the skin of all people are found Demodexes, which supposedly under aggravating circumstances cause blepharocon-junctivitis, rosacea, and discoid lupus erythematosus.Method: The accidental fact of viewing up to 15 Demodexes from a point place of the prob-lem area of the patient’s face with Discoid Lupus Erythematosus served as an occasion for conducting own independent studies. In the first sixyears were monitored natural spread of Demodecosis among surrounding people. Subsequently, with the participation of specialists, all stages ofthe research were spending to prove the scientific discovery, including the reproduction of Demodecosis in the clinic (1980) and the experiment(1981). Results: An examination of the entire skin in 1981 revealed the presence of an initial stage of Demodecosis in 96% of 388,780 people. Astudy of the skin condition of open parts of the body of residents and guests of Almaty showed a catastrophic decrease in the number of peoplewith healthy skin by the end of 1981. A similar result revealed an examination of the skin of open parts of the body in 3 million people from 15 cit-ies in Europe and Asia. In 98.9% of 17823 acarologically examined Demodexes were found. Mites were not found in healthy skin of 28 people. De-modex colonies were found in the skin papules of 242 people with itchy diseases, 247 people with acne, 18 people with atheromas, and 12 peoplewith halazion. Dermatophagoidesses were found in the biotope of 412 patients, but exclusively Demodexes were isolated from their skin. Amongapplicants 57,7% had allergological diagnoses, 37.4% had dermatological diagnoses, 3.6% had other diagnoses. Only 1,3% patients were without adiagnosis. A positive result of antidemodecosis treatment in 92% of 43198 patients testified that they had the clinical masks of Demodecosis. Con-clusion: The results of 46 years of observation indicate that allergies and a number of changes in the skin are a syndrome of undiagnosed HumanDemodecosis, which elimination can provide the elimination of Demodex-associated allergies and skin changes.

PE27-5 Cutaneous manifestations in patients with systemic metal allergy

Kazuo Takahashi1), Zenro Ikezawa2), Junichi Iwata3), Chie Miyabe1), Takaharu Ikeda1), Tamihiro Kawakami1) (Division of Dermatology, TohokuMedical and Pharmaceutical University, Japan1); Ai Dermatology & Allergology Clinic, Japan2); Department of Dermatology, Atami Hospital, In-ternational University of Health and Welfare, Japan3))

Background: Systemic metal allergy is rare and can be difficult to diagnose. This condition is associated with the ingestion of metal-containingfoods and the absorption of dental metal. Metal patch testing is utilitarian and can be used as a screening tool for metal allergy but is not essential.The types of eruptions are various though cutaneous manifestation on the palm and sole is a typical phenotype, and the disease state and onsetmechanism are not uniform.Materials and Methods:We retrospectively investigated patients with systemic metal allergy. We performed metalpatch tests to screen patients with generalized intractable dermatitis localized to the palms and soles and/or covering the whole body. Eightcases of metal allergy were diagnosed after the patients were treated with removal of dental metal and a low-metal diet for those with a positivemetal patch test. Results:We reviewed 8 patients with systemic metal allergy, with an average age of 66.3 (4877) years. Five (63%) of the patientspresented with specific cutaneous findings on the palmar and plantar. Three (37%) had generalized eczema, and another 3 (37%) had palmar andplantar pustulosis. Nickel patch test was positive in 4 (50%) patients. Results for other metals are as follows: cobalt allergy, 3 cases; chromium al-lergy, 1 case; iridium allergy, 3 cases; palladium allergy, 2 cases; copper allergy, 2 cases; and zinc allergy, 3 cases (with overlap). The cutaneousmanifestations disappeared after the patients were placed on a diet with low content of the culprit metal and/or by removal of the culprit metalwith dental treatment. Conclusion: Metal patch testing should be performed to investigate the possibility of metal allergy for a patient with re-fractory cutaneous manifestations especially on the palmar and plantar. If these findings coexist with a positive metal patch test, a low-metal dietand/or the removal of dental metals should be considered for individuals with positive metal patch tests.

PE27-6 Daily emollients and protective gloves for treatment of hand eczema: an open-labeled pilot study in medical professionals

Sayaka Kuwatsuka1), Yutaka Kuwatsuka1), Saori Tomimura1), Motoi Takenaka1), Yoko Terasaka2), Koichi Izumikawa2), Yoshitomo Morinaga3,4),Katsunori Yanagihara3), Hiroyuki Murota1) (Department of Dermatology, Nagasaki University Hospital, Japan1); Infection Control and EducationCenter, Nagasaki University Hospital, Japan2); Department of Laboratory Medicine, Nagasaki University Hospital, Japan3); Department of Microbi-ology, Faculty of Medicine, University of Toyama, Japan4))

Background: Hand eczema is one of the major occupational disease, and decreases the quality of life and work productivity. Especially medicalprofessionals seemed to have more higher incidence of hand eczema because of their high frequency of both hands washing and exposure to anti-septics. Eczema can be a cause of bacterial growth, and may make it difficult to maintain clean condition. Decreasing hand eczema will help toprevent nosocomial infection. In this study, the impact of moisturizing intervention for hand eczema was investigated by evaluating moisture-retention and microbiome.Methods and Subject: Eight NICU/GCU nurses with moderate to severe hand eczema and 8 NICU/GCU nurses with-out hand eczema (control subjects) were recruited to this study. They were asked to apply moisturizer 4 times per day and to wear assignedgloves every night time for 4 weeks. In this study, two type of gloves, one was cotton glove and another was malate-dependent moisturizingglove, were used to wear differently on each hand. On before, 1 week after, and 4 weeks after the intervention, Hand Eczema Severity Index(HECSI), the Eczema Area Severity Index (EASI), stratum corneum water content, barrier index, hand microbiome, Dermatology Life Quality In-dex (DLQI), Treatment Satisfaction Questionnaire for Medication (TSQM)-9, Numerical Rating Scale (NRS) were evaluated. Results: Skin symp-toms (HECSI, EASI, stratum corneum water content, barrier index) significantly improved after the intervention. There was no significant im-provement in bilateral difference (glove type), DLQI, and NRS. Patient satisfaction (TSQM-9) were confirmed with some degree. Hand microbiomedid not differ between the hand eczema group and the healthy control group before and after the intervention. Conclusion: Our pilot study foundthat the moisturizing intervention could decrease the severity of hand eczema without regard for the type of gloves. Furthermore, this study im-plicated that hand microbiome might not be affected by moisturizing intervention.

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PosterSession

PE27-7 Effect of Topical Immunotherapy with Squaric Acid Dibutylester for Alopecia Areata

Satoshi Fukushima, Keisuke Sakai, Satoru Mizuhashi, Masatoshi Jinnin, Takamitsu Makino, Yuji Inoue, Hironobu Ihn (Department of Dermatol-ogy, Kumamoto University, Japan)

Background: The Japanese guidelines for the treatment of alopecia areata list topical immunotherapies as a drug therapy for this condition. How-ever, there is insufficient evidence of its efficacy to support this recommendation. Thus, we sought to clarify the effect of topical immunotherapyon the progression and severity of alopecia areata in Japanese patients. Methods: To evaluate the effect of topical immunotherapy with squaricacid dibutylester (SADBE) in alopecia areata patients, we performed a retrospective cohort study on 49 alopecia patients who had received topicalimmunotherapy with SADBE. Patients were evaluated by the change in alopecia severity at 6 and 12 months after the initiation of topical immu-notherapy. The improvement rate was calculated by determination of the complete and partial responses rate to treatment with topical immuno-therapy by application of SADBE. Results: The improvement rate in all alopecia patients treated with SADBE topical immunotherapy was 57.8%.(complete response; 11.1% and partial response; 46.7%). Conclusions: Topical immunotherapy with SADBE is an effective treatment for alopeciaareata. Therefore, the current treatment recommendations for alopecia areata with topical immunotherapies are appropriate.

PE27-8 Activated extrinsic coagulation factors induce degranulation of human skin mast cells and basophils through complement

Yuhki Yanase1,2), Yoshimi Matsuo1), Tomoko Kawaguchi1), Kaori Ishii1), Kazue Uchida1), Shunsuke Takahagi1), Michihiro Hide1) (Department of Der-matology, Hiroshima University, Japan1); Department of Pharmacotherapy, Hiroshima University, Japan2))

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by almost daily recurring wheal and flare with itch and pruritus onanywhere on the body for more than 6 weeks in association with degranulation of mast cells and/or basophils. However, detailed mechanism ofmast cell- and basophil-activation in CSU has been unclear. Recently, the involvement of the extrinsic coagulation pathway triggered by tissue fac-tor (TF) has been suggested in the pathogenesis of CSU. We previously demonstrated that vascular endothelial cells synergistically expressed TFon their surface by the treatment with histamine and LPS in vitro. Moreover, we recently clarified that TF expression of peripheral monocytes inpatients with CSU is significantly enhanced compared to healthy donors. Since, several coagulation factors are serine protease, they can activatetarget cells via protease-activated receptors (PAR-1/2/3/4). We also demonstrated that TF activate the extrinsic coagulation pathway and pro-duced activated-coagulation factors, such as Xa and IIa, resulting in the gap-formation of endothelial cells via PAR-1. In this study, we investigatedif activated extrinsic coagulation factors, Xa and IIa, directly or indirectly activate human skin mast cells and peripheral basophils. Although hu-man skin mast cells and basophils express PAR-1/2 receptors, they were not activated by PAR-1/2 agonists or activated coagulation factors. Onthe other hand, complement C5a produced by the activated coagulation factors from C5 in vitro, induced degranulation of mast cells and baso-phils. Moreover, the reactions were abolished by the treatment with a C5a receptor antagonist. Thus, we here demonstrated that C5a, but not ac-tivated extrinsic coagulation factors, induces degranulation of human skin mast cells and basophils via C5a receptor. Combined application of C5areceptor antagonist and H1 anti-histamines could be more effective treatment for patients with severe and refractory CSU.

PE27-9 Long-term efficacy and safety of lanadelumab in patients with hereditary angioedema: interim results from the HELP open-labelextension study

Neil Inhaber1), Marc A Riedl2), Paula J Busse3), Raffi Tachdjian4), Daniel Soteres5), James Hao6), Peng Lu6), Aleena Banerji7) (Takeda PharmaceuticalCompany Limited, USA1); Division of Rheumatology, Allergy & Immunology, University of California San Diego, USA2); Division of Allergy andClinical Immunology, Icahn School of Medicine at Mount Sinai, USA3); AIRE Medical of Los Angeles, University of California Los Angeles, USA4);Asthma and Allergy Associates PC, USA5); Shire, a Takeda company, USA6); Massachusetts General Hospital, Harvard Medical School, USA7))

Background: Lanadelumab was generally well-tolerated and effective in preventing attacks in patients with hereditary angioedema (HAE) dur-ing 26 weeks’ treatment in the HELP study. Long-term safety and efficacy of lanadelumab are being assessed in the ongoing HELP open-label ex-tension study (OLE; NCT02741596).Methods: Patients were ≧12 years old with type 1/2 HAE.“Rollovers”continued into the OLE after complet-ing the HELP study, and“nonrollovers”entered the OLE if they had a historical baseline of ≧1 attack/12 weeks. Rollovers received a single 300mg lanadelumab dose on Day 0, then 300 mg Q2W after their first attack. Nonrollovers received 300 mg Q2W starting on Day 0. Data were col-lected up to 31August2018. Results: A total of 212 patients (n=109 rollovers, n=103 nonrollovers) received lanadelumab over a median (range) of20.7 (026.1) months; 186 (87.7%) remain in the study. TEAEs were reported in ～95% of patients; most were mild/moderate in severity. The mostfrequent treatment-related TEAE was mild injection site pain. Six (2.8%) patients discontinued from the study due to TEAEs; one was treatment-related (injection site papules). No treatment-related serious TEAEs or deaths occurred. Anti-lanadelumab antibodies were detected in 21 (9.9%)patients; 6 (2.8%) were positive for neutralizing antibodies with no apparent clinical impact. Lanadelumab markedly reduced the attack rate inoverall patients from a mean of 3.05 attacks/month at baseline to 0.26 attacks/month during treatment (87.0% reduction). 90.9% of patientsachieved an attack rate reduction ≧70%. In 57.9% and 78.0% of patients, the maximum attack-free period lasted ≧12 and ≧6 months, respec-tively. Conclusions: Consistent with HELP, lanadelumab prevented attacks during extended experience with 300 mg Q2W. The safety profilewas consistent with HELP; no major safety concerns emerged during the treatment period.

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PE27-11 Metal patch testing in patients with oral symptoms

Misato Maeno1), Risa Tamagawa-Mineoka1), Yukiyasu Arakawa1), Koji Masuda1), Tetsuya Adachi2), Norito Katoh1) (Department of Dermatology,Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan1); Department of Dental Medicine, Kyoto Prefectural Univer-sity of Medicine, Japan2))

Background: Patients with metal allergy has increased recently, and patch testing is a useful investigation in those patients. However, there arefew reports that analyzed the results of metal patch testing based on oral symptoms, and the efficacy of restoration removal has been controver-sial. Our purpose of this study was to investigate the relationships between oral symptoms and metal allergy. Methods: We conducted a retro-spective analysis of 60 patients tested in our department from April 2008 to December 2016. Those patients with oral symptoms were patchtested with the metal series. Results were evaluated using International Contact Dermatitis Research Group (ICDRG) scoring system. Reactionsof more than + were regarded as positive. Results: The most frequent oral symptom was oral abnormal sensation. Results showed that 38 percentof the patients had one or more positive allergic reactions. Nickel was the most common metal allergen. Patients with cheilitis and dysgeusia had50 percent positivity rate. Of the 7 patients whose restorations were removed, 1 patient achieved complete remission and 2 patients showed par-tial remission. Some restorations were removed even though they did not contain patch test positive-metals. We also compared the efficacy of re-moving restorations in two groups. One group had the removal of restorations containing metals with positive patch tests. The other group hadthe removal of restorations containing metals with no positive patch tests. Interestingly, the latter group showed more efficacy by restoration re-moval. Conclusion: Our results showed the difficulty in predicting the efficacy of restoration removal only based on patch testing results. It is pos-sible that effect of removing a metal as a foreign body and the false negative results of patch testing might lead to the effectiveness of removing ametal with a negative patch test.

PE27-12 RUDY JAPAN: Hereditary angioedema (HAE) online registry using information and communication technology (ICT)

Ryo Saito1), Kazumasa Iwamoto1), Akio Tanaka1), Kazuto Kato2), Michihiro Hide1) (Department of Dermatology, Graduate School of Biomedical andHealth Sciences, Hiroshima University, Japan1); Department of Biomedical Ethics and Public Policy, Graduate School of Medicine, Osaka Univer-sity, Japan2))

Background: Hereditary angioedema (HAE) is a rare disease and may develop to life-threatening airway obstruction. The quality of life (QOL) ofpatients with HAE are severely impaired, and the necessity and efficacy of medications for attacks of HAE are largely variable among patients.However, the real word situation of patients with HAE in Japan still remained to be elucidated. Rudy is an online research system developed by aresearch team at the University of Oxford to collect information about rare disease and to develop clinical care for patients using ICT. This sys-tem has been adopted into Japan by Kato lab at Osaka University as RUDY JAPAN in partnership with Rudy and patients with rare diseases. Weintegrated HAE into RUDY JAPAN to get the patients driven information about HAE.Method: Participants can record online anytime the infor-mation such as when and in which body parts the edema developed, whether they received therapies for the attacks, and it worked or not. Par-ticipants may also answer the questionnaires of QOL. We analysed the data during 10 months since the HAE registry started. Results: Eight par-ticipants were registered, and 8 attacks of 5 participants were recorded in this period. Five attacks were presented as digestive symptoms, andsix attacks were treated with medications. Three of them were treated by the self-injection of bradykinin B2 receptor blocker at home. Partici-pants answered that two attacks restricted their daily life activities. Conclusion: The HAE online registry system RUDY JAPAN may inform uspatients driven information and may reflect unmet needs of the patients. We have added angioedema quality of life questionnaire (AE-QoL) to thissystem and expect to obtain more practical information from a viewpoint of patients. The number of participants is still insufficient, and the in-crease of participants and collection of valuable information are expected.

PE27-13 Self-administration of icatibant for the treatment of angioedema attacks: findings from the Icatibant Outcome Survey (IOS)

Marcus Maurer1), Hilary Longhurst2,3), Werner Aberer4), Laurence Bouillet5), Anete S Grumach6), Jaco Botha7), Irmgard Andresen7),Giorgio Giannattasio7), Teresa Caballero8) (Charité Universitätsmedizin Berlin, Germany1); Addenbrooke’s Hospital, Cambridge University Hospi-tals National Health Service (NHS) Foundation Trust, UK2); University College London Hospitals, UK3); Medical University of Graz, Austria4); Na-tional Reference Centre for Angioedema, Grenoble University, France5); University Center Health ABC, Brazil6); Shire (Takeda PharmaceuticalCompany Limited.), Switzerland7); Hospital Universitario La Paz, Biomedical Research Network on Rare Diseases (CIBERER, U754), Spain8))

Background: The international guideline for the management of hereditary angioedema (HAE) recommends that all attacks be considered for on-demand treatment, attacks are treated as early as possible, and patients are taught to self-administer appropriately licensed treatment (Maurer etal. Allergy 2018;73:1575-96). A recommended therapy option is icatibant, a bradykinin B2 receptor antagonist, evaluated (Aberer et al. Allergy2014;69:305-14) and approved for treatment of acute HAE attacks. The Icatibant Outcome Survey (IOS; NCT01034969) is an ongoing internationalregistry initiated in 2009 to monitor the real-world safety and effectiveness of icatibant. Here we report utilization and treatment outcomes withself-administered icatibant in IOS patients. Methods: Descriptive analyses are reported for patients enrolled in 13 countries (July 2009July 2019).Treatment outcomes were analyzed amongst patients who reported 1 icatibant-treated attack with known administration type (self [patient/caregiver] vs healthcare professional [HCP]). Results: Since initiation, 816 patients have received icatibant in IOS; 7,638 attacks in 714 patientswere treated with icatibant, 6177/6494 (95.1%) self-administered (with frequency progressively increasing from 2009-2018) and 317/6494 (4.9%)HCP-administered. Although median (range) time to first injection (1.3 [0.096.0] vs 2.1 [0.094.0] hours), time to resolution (6.0 [0.099.5] vs 5.0 [0.098.3]hours), and attack duration (9.0 [0.099.0] vs 9.7 [0.5100.0] hours) were not significantly different between self-administration and HCP administra-tion, mean±SD time to first injection and attack duration were significantly shorter with self-administration (4.2±7.8 vs 7.4±15.0, p<0.001, and17.3±19.6 vs 21.3±23.8, p=0.03, respectively). Time to resolution after self-administration was shorter with early treatment (<2 vs 2 hours; me-dian: 4.8 [0.096.0] vs 9.0 [0.0100.0]; mean: 10.9±15.5 vs 17.8±20.0; p<0.0001), but not significantly different after HCP administration (median: 4.5[0.096.0] vs 9.1 [0.065.0]; mean: 14.7±23.5 vs 16.6±17.6 hours; p=0.63). Icatibant-related adverse events (AEs) and serious AEs were reported in4.7% and 0.5%, respectively. Conclusion: Self-administered icatibant offers the opportunity for earlier treatment of attacks, as recommended byguidelines, and in IOS resulted in shorter attack duration than HCP administration.

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PE27-14 Prodromes and attack triggers in Canadian patients with hereditary angioedema

Jane Hsieh1), Jacquie Badiou2), Rozita Borici-Mazi3), Teresa Caballero4), Amin Kanani5), Gina Lacuesta6), Christine McCusker7), Susan Waserman8),Stephen Betschel9) (Department of Medicine, University of Toronto, Canada1); Hereditary Angioedema (HAE), Canada2); Department of Medicine,Queen’s University, Canada3); Hospital Universitario La Paz, Spain4); Department of Medicine, University of British Columbia, Canada5); Depart-ment of Medicine, Dalhousie University, Canada6); Department of Immunology, McGill University Health Centre, Canada7); Department of Medi-cine, McMaster University, Canada8); Department of Medicine, University of Toronto, Canada9))

Background: Many patients with hereditary angioedema report trigger factors or prodromal symptoms prior to an attack. Commonly reportedtriggers include mental stress and physical trauma. Frequently reported prodromes include rashes, tingling, nausea, or fatigue. Purpose: To char-acterize the prodromal symptoms and triggers in patients with HAE in Canada. Methods: Ninety HAE patients in Canada participated in ananonymous, online clinical and an HAE specific quality of life questionnaire (HAE-QOL). Eligible patients were literate in either English or French,18 years or older, and had HAE type 1 or 2. Results: Results showed that 75.6% of participants experienced prodromes prior to HAE attacks.There was no association between presence of prodromes and gender. The most frequently reported prodromes were fatigue (46%), rash (32%), ir-ritability (21%), and tingling (13%). Participants reported common triggers such as experiencing stress (91%), trauma (84%), and infection (52%).Prodromal symptoms were not associated with perception of better disease control. Fifty-nine percent of patients with prodromes rated the con-trol of their condition at 4 or 5 out of 5 (5=completely controlled) compared to 44% in the group without prodromes. Prodromal symptoms werealso not associated with higher quality of life scores. For total HAE-QOL, the median score and interquartile range was 107 (89.5 119.5) in patientswho reported prodromes, and 84.5 (61.5-90.5) in patients who did not report prodromes. Conclusion: The frequency and types of prodromes andtrigger factors in our patient populations are in line with the reported literature. The median HAE-QoL score was higher in patients experiencingprodromes, but this result was not found to be significant, possibly due to the sample distribution or other unknown factors. Additional studies arerequired to determine if patients who experience prodromes would have higher quality of life scores or perceive better control over their condi-tion after initiating treatment during prodromes.

PE27-15 Assessment of quality of life and proximity to acute therapy in patients with hereditary angioedema

Jane Hsieh1), Jacquie Badiou2), Rozita Borici-Mazi3), Teresa Caballero4), Amin Kanani5), Gina Lacuesta6), Christine McCusker7), Susan Waserman8),Stephen Betschel9) (Department of Medicine, University of Toronto, Canada1); Hereditary Angioedema (HAE), Canada2); Department of Medicine,Queen’s University, Canada3); Hospital Universitario La Paz, Spain4); Department of Medicine, University of British Columbia, Canada5); Depart-ment of Medicine, Dalhousie University, Canada6); Department of Immunology, McGill University Health Centre, Canada7); Department of Medi-cine, McMaster University, Canada8); Department of Medicine, University of Toronto, Canada9))

Background: Timely access to effective treatment for hereditary angioedema attacks is expected to improve the care of patients, the patient’sperception of control over their disease, and their quality of life. Purpose: To examine the quality of life of Canadian patients with HAE (heredi-tary angioedema) regarding: 1) the impact of having treatment available at home to treat attacks, 2) living close to their HAE specialist, or 3) livingclose to a hospital. Methods: Ninety HAE patients in Canada participated in an anonymous, online clinical and an HAE specific quality of life(HAE-QoL) questionnaire 5. Eligible patients were literate in either English or French, 18 years or older, and had HAE type 1 or 2. Questions in theHAE-QoL covered seven domains: 1) physical functioning and health, 2) disease related stigma, 3) emotional role and social functioning, 4) concernabout offspring, 5) perceived control over illness, 6) mental health, and 7) treatment difficulties. Results: Patients who were <30 minutes awayfrom the nearest hospital compared to patients who were 30 minutes to 2 hours away from the hospital had higher total HAE-QoL scores andscores on the HAE-QOL domains (p<0.05). For total HAE-QoL scores, the median scores and interquartile ranges were 110 (95-122) for patientswho travel <30 minutes, 84.5 (61.5-90.5) for patients who travel > 30 minutes, and 107 (90-114) for self-injected groups. Those who self-injectedtreatment for attacks at home also had higher total QoL scores than those who were >30 minutes away from the hospital (p<0.05). Conclusion:This is the first study to use the HAE-QoL to assess Canadian patients with HAE. Patients who have timely access to treatment, either by living<30 minutes from the nearest hospital or having treatment at home/for acute attacks, have higher total HAE-QoL scores than those who do nothave access to self-administered acute treatment or who live farther away from the hospital.

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Poster Session 28Pediatric asthma 1

PE28-3 Automated decision support system as a screening tool in diagnosis of chronic non-specific bronchopulmonary disease in pedi-atric population- primary health care experience and literature review

Ilgar Mustafaev1), Veronica M Samedi1,2), Lala Allahverdieva1) (Azerbaijan Medical University, Azerbaijan1); University of Saskatchewan, Canada2))

Purpose: The purpose of the study is to develop, validate and test the effectiveness of an automated decision support system (ADSS) for screen-ing and management of chronic nonspecific bronchopulmonary diseases (CNBPD) among pediatric population at the primary health center (PHC).Materials and Methods:We developed and implemented a computer-based decision support system (ADSS) for early diagnosis and managementfor CNBPD on the base of questionnaire developed at the Pediatric Pulmonology Laboratory, St. Petersburg State Medical University. ADSS wasvalidated and tested on 428 patients aged between 6-15 years during visits at PHC. The prevalence of various forms of CNBPD, and the basic de-terminants of immunological status in children were evaluated by specialists during followup visits to the specialized clinics. For the evaluation ofADSS usability, the feedback from the end-users was used. The main factors for evaluation were: time and effort to train the users, willingness touse the system, and physician’s satisfaction with the assistance from the system in the decision-making. Results: ADSS reported data were evalu-ated in 402 patients, with a calculation of CNBPD development probability and a need for specialist referral and further immunological workup.We compared the time needed for a physician to determine the diagnosis and therapy in similar patients, with and without using the system, veri-fying the accuracy of the diagnosis and the appropriateness of the therapy. The ADSS was easy to use and provided with results after 3-5 min-utes from the beginning of the test. Testing of ADSS at the PHC level allowed to identify children with various forms of CNBPD and confirm thediagnosis without additional financial cost. Conclusions: The ADSS was validated and tested at the PHC level. ADSS is a reliable tool for the diag-nosis of CNBPD that resulted in improved patient outcomes and physician performance.

PE28-4 Increase serum eosinophil cationic protein in preschool atopic asthma

Pailin Yooma, Wiparat Manuyakorn, Wasu Kamchaisatian, Suwat Benjaponpitak, Watcharoot Kanchongkittiphon (Department of Pediatrics Al-lergy and Immunology Faculty of Medicine Ramathibodi Hospital, Mahidol University, Thailand)

Background:Wheezing is a common problem in preschool children. Eosinophil cationic protein (ECP) helps evaluate eosinophilic inflammation ofthe airways as a parameter in the assessment of asthma.Methods: Children with recurrent wheezing and healthy non-wheezing control aged 2-5years were enrolled. Subjects were evaluated for skin prick test (SPT) to aeroallergens, fraction exhaled nitric oxide (FeNO), forced oscillationtechnique (FOT), pediatric asthma control test (PACT), and immuneCAP serum ECP level. Results: One hundred twenty-two children were clas-sified into 3 different groups including atopic asthma (n=41), viral-induced wheezing (n=41), and healthy non-wheezing control (n=40). Demo-graphic characteristics demonstrated no significant differences in mean age, body mass index, mode of delivery, and history of tobacco smokingexposure among three groups. There were significant differences in allergic diseases (allergic rhinitis and atopic dermatitis), last wheezing exac-erbation, the number of wheezing, wheeze a part form cold, cough during playing or laughing and PACT scores among groups (P<0.01). Childrenin atopic asthma group had the highest median (IQR) serum ECP levels [6.05 g/L (4.33-10.7)] than that of viral induce wheezing groups [4.84 g/L(2.81- 7.35)] and that of healthy control groups [3.44 g/L (2.33- 7.71)]. In addition, serum ECP was 53.7% detected (22 out of 41) in children with atopicasthma compared to 36.6% (15 out of 41) in viral induce wheezing groups and 30% (12 out of 40) in healthy control groups. Conclusion: Serum ECPmay help in discrimination between atopic asthmatic, viral-induced wheezing and healthy control children. Serum ECP may have a role in identi-fying recurrent wheezing preschool children who needed early anti-inflammatory treatment for their asthma.

PE28-5 Correlation between serum specific IgE and total IgE ratio (sIgE/tIgE ratio) with clinical response in pediatric asthma patientsreceiving allergen-specific immunotherapy

Stephanie Kusbianto, Wisnu Barlianto, Desy Wulandari (Department of Pediatric Allergy Immunology Saiful Anwar Hospital, Faculty of MedicineBrawijaya University, Indonesia)

Background: Allergen specific immunotherapy has been proved to treat allergic asthma and widely use. However, the modalities to evaluateclinical response after immunotherapy are still limited. This study aims to correlate between specific IgE (sIgE) and total IgE (tIgE) ratio and clini-cal response in pediatric asthma patient receiving allergen-specific immunotherapy.Methods: Study participant were twenty children diagnosedwith persistent asthma visiting pediatric allergy-immunology outpatient clinic in Saiful Anwar General Hospital Malang, Indonesia, from March2019-September 2019. All patients were treated with subcutaneous immunotherapy with House Dust Mite (HDM) antigen. The evaluation wasconducted after 14 weeks in the end of build-up phase of treatment. Serum level of specific IgE and total IgE were measured by immuno chemilu-minescence and Enzyme-linked immunosorbent assays (ELISA) methods. Improvement of asthma control was assessed by the Asthma ControlTest (ACT) score. Results: The mean age of children was 6.25±2.73 years old (ranged from 1.5 to 11 years old). There were 11 (55%) male childrenand 9 (45%) female children. In this study, we found that there was significant decrease of sIgE serum level before immunotherapy [9.6 (0.13-49.80)]compared to after immunotherapy [2.06 (0.10-30.9)], p=0.004. Serum tIgE level was decrease significantly before immunotherapy [237.15 (15.28-799.00)] compared to after immunotherapy (98.20 (15.8-451)], p=0.000. There was also significant decrease of sIgE/tIgE ratio before [0.326 (0.004-0.231)] and after immunotherapy [0.249 (0.001-0.219)], p=0.017. There was improvement of ACT score before and after immunotherapy (16.60±1.87and 21.10±2.24 respectively, p=0.000). A significant negative correlation was found between sIgE/tIgE ratio and ACT score (p=0.030, r=-0.484).Conclusion: Allergen-specific immunotherapy decrease sIgE, tIgE serum level, sIgE/tIgE ratio and improved ACT score. There was negativecorrelation between sIgE/tIgE ratio and ACT score. Keywords: sIgE/tIgE ratio; allergen-specific immunotherapy; asthma; ACT

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PosterSession

PE28-6 Prognostic factor analysis for clinical improvement in pediatric asthma patients with house dust mite (hdm) subcutaneous immu-notherapy

Mufida Hariani, Wisnu Barlianto, Desy Wulandari (Department of Pediatric Allergy Immunology, Faculty of Medicine, Brawijaya University, Sai-ful Anwar Hospital, Indonesia)

Background: To date, allergen specific immunotherapy has been widely used in the treatment of asthma. However there is limited study thatevaluate the predictive factors for its clinical response. The aim of this study was to evaluate several factors that could be used to predict the ef-fectiveness of house-dust mite (HDM) subcutaneous immunotherapy in children with asthma.Methods: This study involved 20 children with diag-nosis of asthma in Allergy Immunology Department, Saiful Anwar Hospital who had undergone 14 weeks of standardized HDM subcutaneous im-munotherapy. Demographic data (age and sex) and laboratory parameters (complete blood count, serum specific and total IgE level) were ana-lyzed. Clinical improvement of asthma was assessed by Asthma Control Test (ACT) score. Bivariate analysis and multivariate linear regressionwere used. Results: The mean of age of patients was 6.27±2.76 years old, with 11 patients were male and 9 patients were female. In bivariateanalysis, there were significant correlation of sIgE and sIgE/tIgE ratio with clinical improvement of ACT score (p=0.001, r=-0.667; p=0.016, r=-0.532 respectively). Age, basophil count, sIgE, and sIgE/tIgE ratio were included in multivariate analysis. There was only sIgE serum level thatcorrelate significantly with improvement of ACT score (p=0.001, Adjusted R Square=41.5%). Several other parameters such as sex, tIgE, hemo-globin level, thrombocyte count, eosinophil count, neutrophil-lymphocyte ratio were not significant correlate with clinical improvement of ACTscore (p<0.05). Conclusion: Serum level of sIgE was predictive factor that correlate with clinical improvement in pediatric asthma patients receiv-ing HDM subcutaneous immunotherapy. Keywords: sIgE, prognostic factor, pediatric, asthma, HDM, subcutaneous immunotherapy

PE28-7 A retrospective study of 1600 cases of bronchial asthma hospitalization over 10 years

Takanori Yanai, Hiromi Tadaki, Hiromi Shioya, Yoichi Kaburagi (Department of Pediatrics, National Health Organization Yokohama Medical Cen-ter, Japan)

Background: The prevalence of childhood bronchial asthma (asthma) is about 10% and has remained constant in recent years. The revised guide-lines for asthma have improved the quality of life of patients. However, cases of asthma continue to be hospitalized in primary care settings. Wepresent our experience of asthma hospitalizations during the past 10 years. Methods: Subjects were children with asthma exacerbation or asth-matic bronchitis, who were admitted to our department between May 2010 and December 2019. We analyzed the number of hospitalizationsacross multiple variables which included, year and month of hospitalization, age of the patient, details of treatment, ICS prescription, blood IgEvalues, other hematological parameters, and the number of hospitalizations during the study period. We examined trends by year and risk factorsfor readmission. Results: A total of 1598 cases, there were 1267 asthma exacerbation and 330 asthmatic bronchitis cases. The highest number ofhospitalizations were seen in 2015 (n=228), with a decline thereafter. As for the age group, maximum hospitalizations were seen in the 1-year-old,with a total of 358 cases (22%). The number of hospitalizations did not decrease in the 1-2 years group. 130 patients (8%) received continuous inha-lation of isoproterenol. Pre-hospital ICS prescription was 409 (25%) and post-hospital was 735 (46%). Out of the 692 patients (43%) who were hospi-talized more than once, 358 patients (51%) had a prescription history of ICS. In the subgroup of 2 years and younger, the eosinophil count was sig-nificantly higher in the re-hospitalization group than in the single hospitalization group (183/L vs. 113/L, p<0.01). Discussion:While the number ofother hospitalizations remained constant, the number of asthma hospitalizations in this study decreased around 30% over a period of 10 years. No-tably, 40% of the patients were hospitalized more than once, half of whom were children who received ICS prescription, and no decrease in hospi-talizations was observed in the age group of 1-2 years. High eosinophil count under 2-year-old may be an indicator of re-hospitalization and earlyintervention.

PE28-8 Bronchial responsiveness 5-class model and its association with baseline spirometry and fractional exhaled nitric oxide in chil-dren

Ji Soo Park, Min Jung Kim, Jihye Kim, Yun Jung Choi, Dong In Suh (Department of Pediatrics, Seoul National University Hospital, Republic of Ko-rea)

Rationale: Bronchial hyperresponsiveness, or heightened bronchial responsiveness (BR), is a characteristic feature of asthma affected by struc-tural airway remodeling and airway inflammation. While BR is usually divided into positive and negative according to the provocative concentra-tion (PC) of a methacholine challenge test (MCT), BR actually exists on a continuous spectrum. We propose a 5-class model of BR and show its as-sociation with baseline spirometry and fractional exhaled nitric oxide (FeNO) in children with typical asthma symptoms.Methods: Using a clinicaldata warehouse, we included patients with 1 or more of dyspnea, chronic cough, or wheezing who underwent spirometry, MCT and FeNO. Pa-tients were divided according to BR into 5 groups: Group 1 (PC20<4 mg/mL), Group 2 (PC20 4 and <16 mg/mL), Group 3 (PC20 16 mg/mL and PC15<16 mg/mL), Group 4 (PC15 16 mg/mL and PC10<16 mg/mL), and Group 5 (PC10 16 mg/mL). Results: A total of 117 children were included,with 41 patients in Group1, 32 in Group2, 8 in Group3, 14 in Group 4, and 22 in Group 5. From Group 1 to Group 5, the mean baseline FEV1 z-scoreand FEV1/FVC z-score of each group increased (p for trend 0.002 and 0.002, respectively), and mean FeNO decreased (p for trend 0.01). Conclu-sions: The 5-class model of BR shows significant correlation with baseline FEV1, FEV1/FVC and FeNO in children with asthmatic symptoms.The BR 5-class model successfully reflects both structural airway remodeling represented by baseline spirometry and airway inflammation meas-ured by FeNO.

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PosterSession

PE28-9 Risk of house dust mite sublingual immunotherapy in pediatric patients with allergic asthma

Yuto Kondo1), Hisashi Tanida1), Yasutaka Hirabayashi2), Jun Wakatsuki3), Takayasu Nomura1) (Department of Pediatrics, Nagoya City UniversityGraduate School of Medical Sciences, Japan1); Hibarigaoka Kids Allergy Clinic, Japan2); Wakatsuki Kids Allergy Clinic, Japan3))

Background: Risk of adverse drug reactions (ADRs) during house dust mite (HDM) sublingual immunotherapy (SLIT) has been unclarified in pe-diatric patients with allergic asthma. The goal of this study was to investigate risk factors for ADRs in treatment with HDM sublingual immuno-therapy. Methods:We retrospectively analyzed clinical data of pediatric patients aged 15 years who initiated allergen immunotherapy with theSQ HDM SLIT-tablet (TO-203, Torii, Japan/ALK Denmark) for their allergic rhinitis between February 2017 and September 2019. At the begin-ning of the immunotherapy, their status of allergic asthma was defined based on the Japanese guidelines for childhood asthma 2017. ADRs thatgraded according to the ICS Harmonized Tripartite Guideline E2A and achievement of regular dose of SLIT-tablet within the first 4 weeks of thetherapy were compared between asthma group and non-asthma group. Results: Two hundred and seventeen patients were included in thisstudy. Of these, 99 patients were defined as asthma that includes 63 mild persistent, 29 moderate persistent, and 7 severe persistent as trueasthma severity. We confirmed that their asthma control levels were classified as well-controlled or partially controlled at the beginning of theirSLIT. One hundred and one patients (46.5%) experienced ADRs during the first 4 weeks of the therapy. Comprehensively, frequency of ADRs didnot show any difference between asthma group and non-asthma group. All symptoms were mild and classified as grade 1 except for respiratorysymptom that included 2 cases of grade 2 from non-asthma group. At 4 weeks of the therapy, 7 cases from both asthma and non-asthma groupfailed to achieve 10,000 JAU due to grade 1 symptoms (7.1% vs 5.9%, P=0.79). The SQ HDM SLIT-tablet was well tolerated in pediatric patientswith controlled allergic asthma. Conclusion: Our data suggests allergic asthma is not a risk factor for ADRs in pediatric patients treated withHDM sublingual immunotherapy.

PE28-10 Outcome of preschool asthma in school age: a biomarker-defined cohort study

Kana Hamada, Mayumi Matsunaga, Shingo Yamada, Miyuki Hoshi, Kazutaka Nogami, Taiga Kobori, Keigo Kainuma, Mizuho Nagao,Takao Fujisawa (Allergy Center, National Hospital Organization Mie National Hospital, Japan)

Background: Recurrent wheeze and asthma are one of the most common illness in preschool period. Some of them outgrow asthma while somedevelop persistent asthma in school age. However, factors predicting school-age asthma during preschool period remains to be studied. Predictivebiomarkers are also under investigation. Objective: Our aim was to investigate outcome and risk factors of asthma toward school age in preschoolchildren. Methods: Patients who participated in a randomized controlled trial comparing efficacy of inhaled steroid and montelukast for sympto-matic asthma during preschool age were invited to join the current study seven years after completion of the initial trial. During the trial all theparticipants were tested for specific IgE to house dust mite (HDM) and eosinophil-derived neurotoxin (EDN). ISAAC questionnaire to ask currentand past wheezing and co-morbid allergic diseases was filled out by caregivers. Other background questions were also administered. Then, theywere invited to undergo lung function tests and blood tests for serum IgE, allergen sensitization. Results: Out of 94 patients who participated inthe initial trial, 47 patients replied to the questionnaire and 22 underwent the further tests. In the last 12 months, 15 patients (32%) had wheezing.Seventeen patients (36%) had asthma controller medication. We defined the subjects with current wheezing and/or medication as asthma (n=21,45%) and those with no current wheezing nor medication as non-asthma (n=26, 55%). Prevalence of allergic rhinitis was 95% and 81% in asthmaand non-asthma groups. Atopic dermatitis was 52% and 35%. Proportion of parental asthma was significantly higher in asthma. Specific IgE toHDM at the initial trial, there was no difference between asthma and non-asthma. Also, EDN at non-asthma was higher, but there was no signifi-cant. Non-asthma reduced EDN due to treatment response, but there was no significant. Lung function test was generally better in asthma. Con-clusion: 45% patients had wheezing now and/or used asthma controller medication. Specific IgE to HDM and EDN at the trial was no significantbetween asthma and non-asthma.

PE28-11 Recent practice patterns and variations in children hospitalized for asthma exacerbation in Japan

Kenta Horimukai1), Yusuke Okubo2,3,4), Nobuaki Michihata5), Kojiro Morita4), Hiroki Matsui4), Kiyohide Fushimi6), Hideo Yasunaga4) (Department ofPediatrics, Jikei University Katsushika Medical Center, Japan1); Department of Epidemiology, University of California, Los Angeles, FieldingSchool of Public Health, United States of America2); Department of Social Medicine, National Center for Child Health and Development, Japan3);Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Japan4); Department of HealthServices Research, Graduate School of Medicine, The University of Tokyo, Japan5); Department of Health Policy and Informatics, Tokyo Medicaland Dental University Graduate School of Medicine, Japan6))

Background: High antibiotic prescribing rates for adults with an asthma exacerbation have been reported in developed countries, but few stud-ies have assessed the variation of antibiotic and adjunctive treatment in the routine care of children. Methods: Using data on 54,981 children hos-pitalized for asthma exacerbation with no indication of bacterial infection during 20102018, we conducted a retrospective observational study toassess the trends in initial treatment patterns and their variations. Mixed-effect generalized linear models were used to investigate the treatmenttrends. Hierarchical cluster analyses were performed to classify the treatment variations across hospitals. Results: Overall, 54,981 children wereeligible to the study. Proportions of antibiotic use decreased from 47.2% in 2010 to 26.9% in 2018. Similarly, utilization of antitussive, antihistamines,and methylxanthine showed decreasing trends over the period, whereas the use of mucolytics and ambroxol increased. These treatment vari-ations were more considerable in hospital levels than in 47 prefecture levels. Hierarchical cluster analyses classified these patterns into 6 groupsmostly based on mediator release inhibitor, ambroxol, and antitussive. Conclusions:Wide variations in antibiotics and adjunctive treatments wereobserved across hospital levels. Our findings support the improvement in reducing inappropriate antibiotic use and highlight the need for com-parative effectiveness research of the adjunctive treatments among children hospitalized for asthma.

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PosterSession

PE28-13 The structure of sensitization by allergens in children with allergic diseases in Azerbaijan

Tahira Panahova (Department of Children’s Diseases, Azerbaijan)

Background: The progressive increase in the frequency of allergic diseases in recent decades around the world determines the relevance of find-ing effective diagnostics. To determine the structure of sensitization by allergens in children with allergic diseases. Objective: The object of thestudy was patients with allergic diseases of Azerbaijani nationality who were on outpatient treatment in a private MS clinic.Methods: The studyincluded 202 patients aged 1 year to 17 years, 151 patients with allergic rhinitis (first group), 69 with allergic bronchial asthma (second group) be-tween 2016 and 2018. The average age was - (7.1±0.2) years. By gender, in both clinical groups of patients there is a clear predominance of males(in I 55.6%, in II 66.7%). For an accurate diagnosis of allergies, the ImmunoCAP method was used. Results: High sIgE scores were detected, thelevel in group I 29.2±2.8 kU/L (95% CI 23.6-34.7), in group II - 40.1±4.1 kU/L (95% CI 23.6-34, 7, F=4.806, p<0.029). Signs of allergy in the firstgroup to house dust mite d1 - 80.3%, d2-86.6% of patients, with a pollen allergy, a mixture of herbs gx1 was detected more often - у26.7% of pa-tients, w9 - at 57.1%, sensitization to mold allergens mx2-at 19.1%, m6-at 43.8%, food allergens - to a mixture of food products fx5 - 46.4%, at 31.3% - f4 wheat, in 27.8% - f1 egg protein, in 33.3% - f2 cow’s milk, in 54.5% - t9 olive. When comparing the sensitization spectrum between the groups, dif-ferences in w9 by Mann-Withey p=0.033 were obtained. For children of the second group relative to the first group, there was a high frequency ofsensitization to household allergens, house dust mite d1 - 97.8%, d2-97.8% of patients, of food allergens f2 cow milk in 35.7%. Conclusion: The Spec-trum of sensitization in children of the Azerbaijani population with allergic diseases revealed high levels of sIgE antibodies to house dust mitesand cow’s milk.

PE28-14 Sex differences in effects of lung function on body composition in peri-pubertal status

Ju Hee Kim1), Jun Ah Kim1), Dong Keon Yon1), Eun Kyo Ha2), Hye Mi Jee1), Seung Won Lee3), Man Yong Han1) (Department of Pediatrics, CHA Bun-dang Medical Center, Republic of Korea1); Department of Pediatrics, Kangnam Sacred Heart Hospital, Republic of Korea2); Department of DataScience, Sejong University College of Software Convergence, Republic of Korea3))

Background: At puberty, sex hormones influence on the body composition and lung function. However, little is known about the extent to whichbody composition changes when sex hormones influence small airway lung function although pulmonary function improvement is achieved in thepubertal stage. Objective: Our hypothesis is that sex hormone profile positively affects body composition, especially skeletal muscle mass and freefat mass, and its effects influence small airway lung function in adolescent. Methods: We prospectively recruited 620 children (10-12 years-old)who participated in the SAP2017 cohort. This study provided assessments of pubertal status with breasts and genitals development according to5 Tanner stages by the questionnaire and line drawings and each subject’s blood sex hormone profile (estrogen and testosterone). Impulse oscilla-tion system for evaluation of small airway lung function and multifrequency bioelectrical impedance analysis for evaluation of body compositionwere conducted. The effects of sex hormones on the body composition of small airway lung function were evaluated by mediation analysis. Re-sults: Among total of 620 children enrolled, 503 (81.1%) children met the study criteria. In boys, testosterone had a total effect on reducing lung re-sistance (β=-0.13, 95% CI, -0.21 to -0.05, p<0.001), and in this process the mediating effect through the muscle fat ratio was β=0.19 (95% CI, 0.04 to0.59, P=0.02). In contrast, in girls, secondary sexual characteristics also had a total effect on reducing lung resistance (β=-0.27, 95% CI, -0.58 to-0.05, p=0.04), but in this process the mediating effect through body mass index was β=-0.51 (95% CI, -2.44 to -0.04, P=0.04). Conclusions: In boysduring puberty period, muscle fat ratio had a positive mediating effect on lung resistance lowered by testosterone. On the other hand, in girls dur-ing puberty period, the effect of development of secondary sexual characteristics on improvement of lung resistance was partially masked by anincrease in BMI.

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Poster Session 29Pediatric asthma 2

PE29-1 Clinical characteristics of asthmatic adolescents with versus without persistent bronchial hyperresponsiveness

Younghwan Kim, Yoon Young Jang, Hai Lee Chung (Department of Pediatrics, School of Medicine, Daegu Catholic University Medical Center, Re-public of Korea)

Background: Bronchial hyperresponsiveness (BHR) is considered to be an important physiological feature of asthma and is known to decreasethrough childhood. We aimed to investigate if there are any differences in clinical characteristics of the asthmatic adolescents with vs. withoutpersistent BHR. Methods: Two hundred and fifteen adolescents (13 years of age) who had been diagnosed with asthma before were enrolled.They were divided into 2 groups according to the results of methacholine challenge test: 1) BHR (+) with less than 25 mg/mL of PC20 (N=113) 2)BHR (-) with at or greater than 25 mg/mL of PC20 (N=102). Clinical and lung function parameters were compared between 2 groups. Same studywas done in male and female groups, respectively. The factors related with persistence of BHR were studied in 42 children who were followedfrom age 6 to adolescence. Results: Combined atopic dermatitis, pet allergy, and increased blood eosinophils were related with persistent BHR (P<0.01). Significantly lower %predicted FEV1 and FEV1/FVC ratio were observed in BHR (+) group (P<0.05). Current asthma was significantlymore frequent in BHR (+) group, but also observed in more than 50% of BHR (-) group (74% vs. 52%). Prevalence of current asthma in BHR (+)group was related with severity of BHR (P<0.01). Persistence of BHR was significantly related with atopic sensitization in males, and was signifi-cantly related with lower %predicted FEV1 and FEV1/FVC ratio in females. Severity of BHR at age 6 was significantly associated with persis-tence of BHR in adolescence (P<0.05). Conclusions: Our study showed the clinical factors that might be related with persistent BHR during ado-lescence in asthmatic children. It also suggests that the relationship between those factors and persistence of BHR is different in those of male andfemale. Keywords: asthma, bronchial hyperresponsiveness, children

PE29-2 The modified pulmonary index score as an indicator of hospitalization for acute asthma exacerbation in children with fever

Ryohei Suzuki, Nagatoshi Sagara, Akiko Aota, Kenichi Akashi, Toshio Katsunuma (Department of Pediatrics, Daisan Hospital, The Jikei Univer-sity School of Medicine, Japan)

Background: The Modified Pulmonary Index Score (MPIS) is a highly objective and reproducible indicator for evaluating acute asthma exacerba-tion in children. It may help physicians in making clinical decisions about whether or not to hospitalize a patient with acute asthma exacerbation.However, one of the six items assessed by the MPIS is heart rate, which may be affected by fever. Objective: To clarify whether the MPIS cutoffvalues used for predicting hospitalization are influenced by the presence or absence of fever. Method: The relationship between MPIS scores atthe time of medical examination and the decision to hospitalize the patient or not was evaluated for pediatric patients with acute asthma exacer-bation presenting at our emergency outpatient ward in the period from November 2013 to October 2018. The MPIS of febrile patients was ad-justed for body temperature and its relationship with hospitalization was re-evaluated. Results: The cutoff value of the Modified Pulmonary IndexScore (MPIS) at which the hospitalization probability of a patient with fever is 80% was 9.7 and 9.5 before and after correction for body tempera-ture (95% confidence interval=8.911.1 and 8.610.9), respectively. Conclusion: The MPIS can be used an evaluation method for patients with acuteexacerbation of asthma with fever.

PE29-3 Study of eight cases of pediatric bronchial asthma attacks requiring intensive care management in Fukushima Prefecture

Ryo Maeda1), Kazufumi Yaginuma1), Yasushi Saito1), Masahiro Watanabe1), Kazuhide Suyama1), Masatoki Sato1), Koichi Hashimoto1),Hiroko Sakuma2), Mitsuaki Hosoya1) (Department of Pediatrics, Fukushima Medical University, Japan1); Department of Pediatrics, Hoshi GeneralHospital, Japan2))

Background: Pediatric bronchial asthma attacks can be triggered by inhaled allergen exposure, poor medication compliance, and respiratorytract infection. However, few studies have examined the triggers and patient characteristics in the most severe cases.Methods: In this retrospec-tive study of eight cases of bronchial asthma attack, treated between April 2017 and August 2019 at the pediatric intensive care unit ofFukushima Medical University’s Department of Pediatrics, patient characteristics were analyzed using medical records. Asthma control statusduring the one-month period preceding the onset of the asthmatic attack was classified into“good”,“relatively good”, or“poor”, according to theJapanese Pediatric Guideline for the Treatment and Management of Asthma 2017 . In addition, pathogens causing respiratory tract infectionswere identified using an antigen rapid diagnostic kit; and for patients who were negative, pharyngeal swabs and aspirated sputum were collected,and RT-PCR was carried out. Results: The patients had a mean age of 5 years and 5 months, and most were hospitalized in autumn. Asthma con-trol status during the one-month period preceding the onset was“good”in three cases,“relatively good”in four cases and“poor”in one case. Inall eight cases, viruses believed to be the pathogens were identified. Rhinovirus was identified in two cases; one case each were respiratory syn-cytial virus, adenovirus, enterovirus, and bocavirus; and both enteroviruses and rhinoviruses were found to coinfect patients in two cases. Conclu-sion: In conclusion, most patients who developed severe asthma attacks and who needed intensive care treatment had had relatively well-controlled asthma during the one-month period preceding the attack; however, their condition was aggravated by a viral infection. It seems thatrespiratory tract infections are important factors that can trigger acute exacerbations of bronchial asthma, and extreme caution is needed whenolder children with bronchial asthma have respiratory tract infections.

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PosterSession

PE29-4 Development and validation of a new control questionnaire to aim for a high level of control for children and adolescents

Mayumi Matsunaga1), Makoto Kameda2), Masanori Ikeda3), Yasunori Ito4), Toshishige Inoue5), Kenichi Tokuyama6), Kota Hirai7),Tomoyo Matsubara8), Yukinori Yoshida2), Mizuho Nagao1), Takao Fujisawa1) (Allergy Center, National Hospital Organization Mie National Hospital,Japan1); Department of Pediatrics, Osaka Habikino Medical Center, Japan2); Department of Pediatrics, Okayama University Graduate School ofMedicine, Japan3); Department of Pediatrics, University of Toyama, Japan4); Department of Pediatrics, Sumitomo Hospital, Japan5); Department ofPediatrics, Saitama Medical University, Japan6); Department of Pediatrics, Tokai University Hachioji Hospital, Japan7); Department of Pediatrics,Dokkyo Medical University Saitama Medical Center, Japan8))

Background:Maintaining good asthma control can minimize future risks such as exacerbation and lung function decline and is a primary goal ofasthma management. To assess asthma control, several questionnaires have been developed based on guidelines such as NAEPP guidelines(USA) and GINA guidelines. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria of control status from theother guidelines, in which it stresses on a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire forassessing and achieving best asthma control in preschoolers (Pediatr Allergy and Immunol 2016; 27: 307-312). Likewise, in this study, we aimed todevelop a questionnaire for children and adolescents.Method: A working questionnaire consisting of 14-items for patients and 34-item for caregiv-ers were administered to 362 asthma patients aged 6 to 15 years and their caregivers. A questionnaire for physicians to determine JPGL-definedcontrol were separately filled out. Logistic regression analysis was performed to construct a model to predict control levels using randomly se-lected set of answers from two third of subjects. Validation was performed by using the remaining set of the answers. Results: A set of 6 ques-tions, including wheezing, uncomfortable chest and self-assessed control status for patients and coughing, dyspnea and rescue beta-agonist use forcaregivers, were selected and the 6-item model showed good statistical fit with AUC of 0.931 and AIC of 159. We named it the Best Asthma Con-trol Test for children and adolescents (Best ACT). The Best ACT scores differed significantly in the hypothetical direction among the groups ofdifferent JPGL-defined control levels, use/non-use of systemic corticosteroids and step-up/down treatment decisions. Conclusions: The Best ACTis a valid questionnaire for children/adolescents aiming for best asthma control.

PE29-5 Classification of wheezing children in rural Bangladesh by intensity of Ascaris infection, total and specific Ig E levels, history ofpneumonia and other risk factors

Haruko Takeuchi1), Alfazal Khan2), Khalequz Zaman2), Sayaka Takanashi3), Tafsir Hasan2), Mohammad Yunus2), Masamine Jimba1), Tsutomu Iwata4)

(Community and Global Health, The University of Tokyo, Japan1); International Centre for Diarrhoeal Disease Research, Bangladesh2); Develop-mental Medical Sciences, The University of Tokyo, Japan3); The Graduate School of Humanities and Life Sciences, Tokyo Kasei University, Ja-pan4))

Background: Ascaris lumbricoides is the most common soil-transmitted helminth and infects 447 million people in impoverished areas worldwideand causes serious morbidity including wheezing by influencing various aspects of human immunity, such as type 2 innate lymphoid cells, regula-tory T cell function and acquired Th2 immunity. We aimed to classify wheezing children to elucidate the effect of Ascaris infection on wheezingin rural Bangladesh.Method:We analyzed relevant data collected in rural Bangladesh in 2001 using hierarchical cluster analysis to determine themechanisms of and the degree to which Ascaris contributes to childhood wheezing based on Ascaris infection intensity and other risk factors.The participants included 219 5-year-old wheezing children who were randomly selected from 1705 children living in the Matlab Health andDemographic Surveillance area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Hierarchical cluster analysis was con-ducted using variables of history of pneumonia, total and specific Immunoglobulin E levels, Ascaris infection intensity and parental asthma. Re-sults: Three distinct wheezing groups were identified. Children in Cluster 1 (n=50) had the highest titers of the total, anti-Ascaris , anti-Dermatophagoides pteronyssinus , and anti-cockroach IgEs, and experienced the fewest episodes of pneumonia. Anti-Ascaris IgE had beenproved to cause wheezing in this group. Cluster 2 (n=114), the largest group, experienced few episodes of pneumonia, had the lowest titers of thetotal, anti-Ascaris , anti-Dp and anti-cockroach IgEs. Cluster 3 (n=32) consisted of participants with the most episodes of pneumonia and lower tit-ers of the total and specific IgEs. The extremely high prevalence of Ascaris infection found in Clusters 1-3 were 78%, 77% and 72%, respectively.Conclusion: Childhood wheezing in rural Bangladesh could be divided into three groups, with 26% of wheezing attributable to anti-Ascaris IgE,which may be comparable to atopic type, and 16% to history of pneumonia during early childhood, comparable to early wheezers, and 58% mighthave been due to Ascaris infection without elevated anti-Ascaris IgE which might be due to Type 2 innate immunity.

PE29-6 Features of respiratory function in pediatric asthma based on the degree of obesity

Takehiko Soutome, Misa Watanabe, Hiroshi Miyashita, Yuki Fujimaki, Yasuho Shoda, Yumiko Komine, Akira Ohara (Department of Pediatrics,Toho University Omori Medical Center, Japan)

Objectives: Obesity is known to cause impaired respiratory function through physical mechanisms in adults with asthma, but how it affects respi-ratory function in children with asthma is not well understood. Therefore, we studied the characteristics of respiratory function in obese childrenwith asthma.Methods:We enrolled 76 outpatients from our hospital. The outpatients were tested for exhaled nitric oxide (eNO), spirometry andMostGraph assessment at least twice between April 2016 and March 2020, without any asthma attacks. The obesity rate was determined basedon body weight and height. Participants were classified into three groups: obese group, over 20; normal group, 020; and lean group, under 0.Asthma severity was assessed using the JPGL 2017 severity score. MostGraph assessments were used to compare the differences from baselineusing the forced oscillation technique age-group reference value prediction equation proposed by Fujisawa et al. We compared patient character-istics, peripheral blood eosinophil counts, non-specific IgE levels, eNO fractions, spirometric parameters (FVC, FEV1.0, MMF, and V50), andMostGraph results among the three groups. Results: Data from 41 boys and 35 girls with a median age of 10.5 years were obtained. Of the partici-pants, 8 were obese, 32 were in the normal range, and 36 were lean. Median the obesity rate was 38.1% in the obese group, 5.0% in the normalgroup, and -5.2% in the lean group. The obese group was older and had more severe asthma at the time of the survey. There were no significantdifferences in asthma treatment, hospital admissions, total IgE levels, or peripheral blood eosinophil counts among the three groups. In respira-tory function tests, there were no significant differences in eNO and spirometric parameters among the three groups. However, in the obesegroup, MostGraph R5, R 20, and Fres values were significantly higher than those in the other 2 groups. Conclusions: In the obese group, therewas no decrease in spirometric parameters without any asthma attacks. However, both airway resistance and elastic resistance were signifi-cantly higher than in the other 2 groups.

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PosterSession

PE29-7 Sex difference, severity of asthma and exercise-induced wheezing among children

Satoshi Honjo1), Yoko Murakami1), Hiroshi Odajima1), Yuichi Adachi2), Koichi Yoshida3), Yukihiro Ohya4), Akira Akasawa Iino5) (Department of Pae-diatrics, National Hospital Organization Fukuoka National Hospital, Japan1); Department of Paediatrics, Faculty of Medicine, Graduate School ofMedicine and Pharmaceutical Science for Education, Toyama University, Japan2); Division of Allergy, Tokyo Metropolitan Children’s MedicalCentre, Japan3); Division of Allergy, National Centre for Child Health and Development, Japan4); Department of Paediatrics, Nasunogahara Clinic,Japan5))

Background:We previously reported the girl dominance over boy in prevalence of exercise-induced wheezing (EIW) among children aged 13 - 15and disappearance of the difference in children aged 16 - 18 (Murakami et al. 2014). In the present study, sex differentials in the risk for higher se-verity of EIW were examined. Subjects and Methods: Current asthmatics with reported history of EIW, 3,213 junior high school children aged13 - 15 and 3,008 high school children aged 16 - 18, were examined. Severity of EIW were defined regarding frequency: every day, >=weekly, notweekly, or no during the past 4 weeks, and risk for the higher severity of EIW due to severity of current asthma was obtained by ordered logisticregression. Results: Among junior high school children, odds ratio (OR) for having higher severity of EIW due to severity of current asthma (noduring the past 4 weeks, not weekly, >=weekly and every day) were 1.0 (reference), 6.0 (95% CI: 5.1 - 7.2), 33.0 (25.9 - 42.0) and 115.1 (71.6 - 184.8), re-spectively, adjusted for sex, degree of obesity and other covariates. For high school children, the corresponding ORs were 1.0, 7.0 (5.9 - 8.4), 34.3(26.6 - 44.3) and 106.6 (63.9 - 177.7), respectively. The interaction between sex and the severity of current asthma was not observed for junior highschool children (p>0.691), while the interaction was suggested for high school children (p=0.13) with more prominent risk for boy; ORs were 1.0,6.7, 38.2 and 129.5, respectively. The interaction between sex and degree of obesity for the higher severity of EIW was not observed for juniorhigh school children (p=0.554) and for high school children (p=0.316). Discussion: Although possible differential effect of sex on the association be-tween severity of current asthma and severity of EIW in children after or during the late phase of puberty was observed, the causal inferenceshould be modest.

PE29-8 Comparison of forced oscillation technique and spirometry in asthmatic children

Takuya Oda, Kota Ikari, Moeri Tsuji, Masaru Kawamura, Junichiro Tezuka (Department of Allergy and Pulmonology, Fukuoka Children’s Hospi-tal, Japan)

Background: The forced oscillation technique (FOT) is a noninvasive test used to characterize the mechanical impedance of the respiratory sys-tem. The aim of the study was to investigate the association between lung function variables, obtained both by FOT and spirometry, and asthmadiagnosis and control in asthmatic children. Methods: We conducted a retrospective cohort study using data from patients with stable asthmawho were performed both MostGraph-02 and spirometry at the same time. Lung function variables were measured in 51 children (age, median 9,range 4-18 years; M:F=35:16), in stable asthmatic children. We defined the obstruction in spirometry (SP+) as either reduced FEV1, reduced FEV1/FVC ratio, or concave flow-volume loop. We used the Japanese pediatric reference values in the parameters of MostGraph-02. Results: The fre-quency of SP+ was in 24 of 43 in which FOT was normal (FOT-), and 7 of 8 in which FOT was abnormal (FOT+). Compared to SP+/FOT- group,SP+/FOT+ group had older age (14 vs 10 years old, p=0.023), longer history of asthma (12 vs 7.5 years, p=0.021). There were no significant differ-ences in the height standard deviation (SD) scores, body mass index (BMI) SD scores, severity of asthma, inhaled corticosteroids use, long-actingbeta agonists use, Asthma Control Test scores, temporary changes of treatment steps, or the incidence of acute exacerbation within 6 months af-ter lung function testing among both groups. Conclusions: There is a subgroup in which spirometry indices airflow obstruction but FOT showsno airway obstruction. Older age and a long history of asthma are associated with the abnormal exam in FOT. However, the prognosis of the sub-group and how to manage those patients are not yet determined. Further studies are therefore required to explore the relationship between base-line lung function using FOT and clinical outcomes in children with asthma.

PE29-9 Objective evaluation of airway hypersensitivity using breath sound analysis: a multicenter, prospective study in children up to 3years old

Manabu Miyamoto1), Shigemi Yoshihara1), Hiromi Tadaki2), Hiromi Shioya2), Hideyuki Tabata3), Hiroyuki Mochizuki3) (Department of Pediatrics,Dokkyo Medical University, Japan1); Division of Pediatrics, National Hospital Organization Yokohama Medical Center, Japan2); Department of Pe-diatrics, Tokai University School of Medicine, Japan3))

Background: Recurrent wheezing occurs in a large population of young children. However, it is difficult to predict who will develop asthma andwho need intervention. Methods: We considered children aged under 24 months and collected their lung sounds before and after inhalation ofshort-acting beta2-agonist (SABA) during their regular medical checkup. The lung sound data were collected with a commercially availablebreath sound analyzer and calculated to the parameters that estimate high-frequency sound suggesting wheezing. We performed a follow-up sur-vey using the original questionnaire based on the ATS-DLD. The primary end point was the development of recurrent wheezing in children agedup to 3 years. Results:We collected lung sound data from 79 children, and 68 children (median age, 8 months; 44% male) were followed up untilthey were 3 years old. All children had normal lung sounds heard through a stethoscope. Twenty-two children (32.4%) developed recurrentwheezing. No association was established between the change rate of the lung sound parameters before and after inhalation of SABA and themorbidity of recurrent wheezing. Children with atopic dermatitis upon recruitment and developed recurrent wheezing, however, responded toSABA significantly compared with the children who had no atopic dermatitis and developed recurrent wheezing on high-frequency lung sounds(P=.049). Conclusion: Recurrent wheezing children with atopic dermatitis already have airway hypersensitivity within early childhood. Lungsound analysis can detect airway sound changes inaudible to the human ear.

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PosterSession

PE29-10 A randomized, single-blind, placebo-controlled study on the efficacy of the Tulobuterol Patch (TP-LABA) in treating acute exac-erbation of chronic bronchitis in children

Chang-Keun Kim1), Eun-Mi Kwon1), Young-Ho Kim1), Zak Callaway1,2), Sang-Hee Jung1) (Department of Pediatrics, Asthma and Allergy Center, InjeUniversity Sanggye Paik Hospital, Republic of Korea1); School of Biological Sciences, University of Ulsan, Republic of Korea2))

Background: Though the tulobuterol patch (TP-LABA) is a currently recommended treatment for acute exacerbation of chronic bronchitis inKorean children, no randomized placebo-controlled study of its efficacy in treating this disease has been published.Methods: A single center, ran-domized, single-blind, placebo-controlled study was performed on 64 pediatric patients aged 6 months to 15 years diagnosed with acute exacerba-tion of chronic bronchitis at the Asthma and Allergy Center of Inje University Sanggye Paik Hospital. A Bronchial Symptom Score (BSS) was as-sessed on Days 0 (Baseline), 7 (Week 1) and 14 (Week 2). The score was calculated by allotting 0-4 points for each of five respiratory symptoms (0=no symptom and 4=maximum severity of symptom) cough, sputum, chest pain, dyspnea, rhonchi. Only patients with BSS 5 at Day 0 were in-cluded. The Quality-of-Life (QOL) score was determined based on the Chronic Respiratory Disease Questionnaire developed by Guyatt et al. Re-sults: The total BSS was significantly decreased in the Active group compared to the Placebo group on Week 1 and Week 2 (P=0.0020, P=0.0055,respectively). There were no differences in the BSS Cough Score and BSS Dyspnea Score between the two groups, while there were significantdifferences in the BSS Sputum Score and Rhonchi Score on Week 1 and Week 2 (P<0.002, P=0.014, P=0.0001, P=0.0001, respectively). The totalQOL Score and Impact Score showed no differences between the two groups. There was no difference for the Medication Adherence Rate andadverse events between the two groups. Conclusion: The TP-LABA can be effective in managing acute exacerbation of chronic bronchitis in chil-dren.

PE29-11 Longitudinal changes in lung function during childhood and adolescence with asthma

Shingo Yamada, Mayumi Matsunaga, Kazutaka Nogami, Kana Hamada, Miyuki Hoshi, Keigo Kainuma, Mizuho Nagao, Takao Fujisawa (AllergyCenter, National Hospital Organization Mie National Hospital, Japan)

Rationale: Recent cohort studies suggest that lung function in childhood tracks to adulthood and that reduced lung function growth in childrenwith asthma may precede accelerated decline of lung function, even, developing COPD in later adulthood. However, risk factors of poor lung func-tion growth in childhood and adolescence are not well known. To this end, we analyzed longitudinal changes in lung function in children and ado-lescents with asthma.Method: A retrospective multi-center study. Asthma patients who had been followed up for 5 years or more during 6 to 18years of age at 6 centers in Japan were enrolled. The patients who had lung function measurements at least 3 times were analyzed in the study.The average value of %FEV1 during each age was adopted as the lung function of each age. Linear regression analyses of the %FEV1 values dur-ing the 2 periods; 6-11 years old (childhood) and 12-18 years old (adolescence) were performed. Based on the slope values from regression analysis,the subjects were divided into 2 groups; decline (D) and elevation (E). Clinical data were retrieved from electronic charts and compared betweenthe groups. Result:A total of 640 patients, 530 during childhood and 402 during adolescence, were enrolled. Of them, 378 patients were in Group Dand 152 were in Group E during childhood and 140 and 262 in Group D and E during adolescence, respectively. Z scores for heights were signifi-cantly lower in Group D during childhood and adolescence compared to normal population. Prevalence of comorbid food allergy (FA) during child-hood, proportion of girls and LABA use during adolescence in Group D were significantly higher than in Group E. Conclusion: Reduced heightgrowth, comorbid food allergy and female gender may be risk factors of early lung function decline. Causal relationship needs to be studied.

PE29-12 Clinical utility of Eosinophil-Derived Neurotoxin (EDN) in diagnosis of asthma inpreschool children with acute wheezing

Taiga Kobori1,2), Mizuho Nagao1), Niclas Rydell3), Takao Fujisawa1) (Allergy Center, National Hospital Organization Mie National Hospital, Japan1);Department of Pediatrics, Odawara Municipal Hospital, Japan2); Thermo Fisher Scientific, Sweden3))

Background: Recurrent wheezing in early life is a common but complex condition with several causes and outcomes. Among them, asthma is achronic inflammatory disease and may persist to later childhood and even adulthood, resulting in unfavorable outcomes such as reduced lungfunction and frequent exacerbations. Thus, early management of asthma based on the right diagnosis is critical. However, current predictionmodels of preschool asthma have only modest accuracy. Novel biomarkers may improve asthma prediction. Eosinophil-derived neurotoxin (EDN)is an eosinophil granule protein that is released during eosinophil activation. EDN has been proved to be a promising marker for eosinophilic in-flammation in severe adult asthma and we recently developed a novel ImmunoCAP platform assay for measurement of EDN and reported thatEDN is useful in diagnosis of asthma in school children (Pract Lab Med 2019). Here, we investigated its utility in preschool children with acutewheezing.Methods: A prospective observational study. Children <6 years of age who presented with acute wheezing were enrolled in the study.Blood samples were obtained during acute and convalescent phases of wheezing. Serum EDN, specific IgE to common allergens such as housedust mite and eosinophil count were measured. Physicians made diagnosis of wheezing subtypes, episodic viral or multiple trigger wheeze (EVW,MTW) based on a classification of ERS task force. Results: A total of 81 children were enrolled in the study. Serum and plasma levels of EDN andeosinophil count during acute wheezing were significantly higher in MTW group than in EVW group. Patients sensitized to aeroallergens had sig-nificantly higher levels of EDN, not eosinophil count, on wheezing than in those who were not sensitized. EDN levels in sensitized patients signifi-cantly decreased from acute to convalescent phases in response to treatment with corticosteroids and bronchodilators. The changes were vari-able in non-sensitized patients. Conclusions: EDN was higher in an asthma-like phenotype of acute wheezing in preschool children and reflectedclinical improvement in response to asthma treatment.

246

PosterSession

PE29-13 Questionnaire survey on the opinions among caregivers about COVID-19 and their clinic visit and children’s cough in a clinic atNagoya city

Manabu Miyamoto1,2), Kazunori Arai3,4), Akihiko Terada5), Naoto Watanabe3), Sohei Makino3), Shigemi Yoshihara1) (Department of Pediatrics, Dok-kyo Medical University, Japan1); Department of Pediatrics, Nasu Red Cross Hospital, Japan2); Tokyo Allergy and Respiratory Disease Research In-stitute, Japan3); Promotion Committee for ILCA (I love clean air) Blue Ribbon Movement, Japan4); Terada Kid’s Allergy and asthma Clinic, Japan5))

Background: To clarify the influences of COVID-19 to the opinions among caregivers about their clinic visit and children’s cough. Methods:Ninety-four caregivers who visited the clinic in Nagoya city during May 2020, were asked to fill in the questionnaires. Results: They had 45 (48%)male and 49 (52%) female children. The age of their children ranges between 1 and 17, the median was 7. Thirty-two (34%), 43 (46%), 16 (17%), and 3(3%) children were classified as 1 to 5, 6 to 10, 11 to 15, and 16 to 20 year old class, respectively. Ninety (96%) children had asthma, and 59 (63%) chil-dren had allergic disease, and 56 (60%) children had both. Eighty-two (87%) of them hesitated to visit the clinic with their children for fear of theirchildren’s getting COVID-19, and 2 (2%) caregivers visited the clinic without their children. Eighty-four (90%) caregivers thought that their chil-dren’s disease would worsen COVID-19 when getting it. Sixty-nine (73%) caregivers selected getting COVID-19 as the most worries, and 2 (2%) se-lected worsening of their children’s disease. Twenty-nine (31%) of them became to be worried about their children’s cough more than beforeCOVID-19 epidemic, while 7 (7%) caregivers felt that their children cough more because of fears about COVID-19. Twenty (21%) of them felt thattheir surroundings took a dislike to the cough of their children, and 8 (9%) caregivers felt that their children were worried about it. Conclusions:In this survey among caregivers visiting clinic, it seemed that they worried about their children’s getting COVID-19, and that they visited theclinic with their children as usual. Some children had more cough than before COVID-19 epidemic, they need careful treatment.

247

PosterSession

Poster Session 30Pollinosis

PE30-1 Relationship between the total tear IgE, serum specific IgE, and total serum IgE levels in patients with pollen allergic conjunctivi-tis

Yasuo Yamana1), Eiichi Uchio2) (Yamana Eye Clinic, Japan1); Department of Ophthalmology, Fukuoka University, Japan2))

Background: Allergic conjunctivitis (AC) cases are often sensitized by various antigens. We aimed to investigate the characteristics of antigensto which patients who have multiple allergies are sensitized.Methods: At Yamana Eye Clinic, total tear IgE (t-tIgE), serum total IgE (s-tIgE), andserum specific IgEs (s-sIgE) tests were performed for the diagnosis of AC. In 2019, 1372 patients obtained a clinical diagnosis of AC. Among thepatients who underwent all the tests, 88 patients tested positive for s-sIgE due to pollen. The subjects were 32 (36.4%) men and 56 (63.6%) womenaged 986 years. Results: A total of 57 (64.8%) patients tested positive and 31 (35.2%) patients tested negative for t-tIgE. With the high total score ofpositive class for pollen-specific serum IgE antibody, the positive rate of t-tIgE was higher (p=0.03). In the s-tIgE test, 47 (53.4%) and 41 (46.6%) pa-tients had s-tIgE levels below and above the reference value of 170 IU/ml, respectively. Of the 57 patients with positive t-tIgE test results, 30(52.6%) patients had s-tIgE levels below the reference value. Of the 41 patients whose s-tIgE levels were above the reference value, 38 (92.7%) pa-tients had s-sIgE antibodies for allergens other than pollen. Among these patients, food-specific serum IgE antibodies, were identified in 27 (30.6)patients; of these patients, 22 (81.5%) and 5 (18.5%) patients tested positive and negative for t-tIgE, respectively. With the high total score of posi-tive class for food-specific serum IgE antibody, the positive rate of t-tIgE was higher (p=0.03). Conclusion: The patients with pollen AC testedpositive for t-tIgE, but their s-tIgE levels were often below the reference value. IgE antibodies for allergies other than pollen were identified in >90% of the patients with s-tIgE levels above the reference value. These results suggest that the pollen AC is caused by sensitization around theconjunctiva. However, with the high degree of sensitization, total IgE levels in tears were higher. Furthermore, t-tIgE level was considered to beaffected by the food-specific serum IgE antibodies.

PE30-2 Revision of threshold levels for evoking pollinosis to oak, pine, Japanese hop, and ragweed in Seoul metropolitan area, Korea

Young Jin Choi1), Kyung Suk Lee1), Jae-Won Oh1), Kyu Rang Kim2), Yung-Seop Lee3) (Department of Pediatrics, Hanyang University Guri Hospital,Republic of Korea1); Applied Meteorology Research Division, National Institute of Meteorological Science, Republic of Korea2); Department of Sta-tistics, Dongguk University, Republic of Korea3))

Introduction: Threshold levels for symptom development of pollinosis are vary among studies and countries.. Objective: This study aimed to en-able the revision of currently used threshold levels. Methods: Oak, pine, Japanese hop, and ragweed pollen samples were collected daily for 8years from Seoul and Guri areas. A total of 792 subjects with allergy to these pollens were recruited. The symptom index (SI) was assessedthrough telephone calls and allergy questionnaires, and data were analyzed using correlation coefficients. Results: The risk index for oak pollenallergy was“mild”when the pollen count was 02 grains/m3,“moderate”when it was 311 grains/m3,“severe”when it was 1228 grains/m3, and

“dangerous”when it was >29 grains/m3. The risk grade for pine pollen allergy was“mild”when the pollen count was 04 grains/m3,“moderate”when it was 542 grains/m3,“severe”when it was 4366 grains/m3, and“dangerous”when it was >67 grains/m3. For Japanese hop pollen allergy,the risk grade was“mild”when the pollen count was 08 grains/m3,“moderate”when it was 910 grains/m3,“severe”when it was 1132 grains/m3, and“dangerous”when it was >33 grains/m3. Lastly, for ragweed, the risk grade was“mild”when the pollen count was 01 grains/m3,“moder-ate”when it was 26 grains/m3,“severe”when it was 733 grains/m3, and“dangerous”when it was >34 grains/m3. Conclusions: Revising thethreshold levels for the risk index for pollen allergies may be very useful for developing pollen prediction models for patients with pollen allergiesin Korea.

PE30-3 The correlation with pollination and increased sensitization rate of pollen allergens of children in Seoul metropolitan area

Kyung Suk Lee1), Young Jin Choi1), Kyunghoon Kim2), Yung-Seop Lee3), Kyu Rang Kim4), Jae-Won Oh1) (Department of Pediatrics, Hanyang Univer-sity Guri Hospital, Hanyang University College of Medicine, Republic of Korea1); Department of Pediatrics, College of Medicine, The Catholic Uni-versity of Korea, Republic of Korea2); Departement of Statistics, Dongguk University, Republic of Korea3); Applied Meteorology Research Division,National Institute of Meteorological Sciences, Republic of Korea4))

Background: Climatic change represents a massive threat to health and influences pollen productions and season that induce allergic manifesta-tions such as asthma, allergic rhinitis. Longer pollen season could increase the duration of human exposure to pollen with consequences for in-creased allergic sensitization Therefore, we investigate the correlation between altered pollen season and in rising sensitization rate to pollen inSeoul metropolitan area for 20 years. Methods:We recruited skin and/or serum allergy test results from individuals who visited Allergic Clinicsof Hanyang University Seoul and Guri hospital. Pollens were calculated and identified at two stations in Seoul and Guri from 1997 to 2019. Theweather from the Korea Meteorological Administration was also recorded daily. The results were assessed by linear regression and time seriesanalysis. The correlation between the duration of the pollen season with starting date and pollen sensitization were assessed by correlation analy-sis. Results: The starting of pollination became earlier, the ending pollination later annually. Tree pollens sensitization rate such as oak, hazel,pine, birch, alder and willow were increased with year. The duration of the pollen season and pollen sensitization rate positively correlated (Oak: r=0.66, hazel: r=0.69, pine: r=0.79, birch: r=0.63, alder: r=0.74, willow: r=0.61). Accumulated temperature and pollen sensitization rate also positivelycorrelated (Oak: r=0.71, hazel: r=0.66, pine: r=0.53, birch: r=0.69, alder: r=0.53, willow: r=0.64). Conclusion: The duration of the pollen season withstarting date and sensitization rate to pollen are increased year by year and they are statistically correlated in Seoul metropolitan area. Accumu-lated temperature also is related to pollen sensitization rate. It demonstrates that climate change influenced pollen season and sensitization rate topollen in Seoul metropolitan children. There are remained the study to evaluate the relationship between a pollen amount and the sensitizationrate to same pollen with allergic symptoms in them.

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PosterSession

PE30-4 Japanese cedar pollen sublingual immunotherapy tablets suppressed the clinical symptoms of Japanese cypress pollinosiswithout additional safety concerns (Ad Hoc Analysis of 206-2-1 trial)

Tomoya Kurokawa1,2), Yuriko Maekawa3), Hisataka Tanaka3), Mitsuhiro Okano4), Kimihiro Okubo5), Yoshitaka Okamoto6) (Clinical Research Center,Chiba University Hospital, Japan1); Otorhinolaryngology, Head and Neck Surgery, Chiba University Hospital, Japan2); Medical Affairs Department,Torii Pharmaceutical Co., Ltd., Japan3); Otorhinolaryngology, International University of Health and Welfare, Japan4); Department of Head & Neckand Sensory Organ Science, Nippon Medical School, Japan5); President, Chiba Rosai Hospital, Japan6))

Background: Japanese cedar pollen dispersal precedes Japanese cypress pollen dispersal, and approximately 70% of patients with cedar pollino-sis are also known allergic to Japanese cypress pollen because of a common antigen. The efficacy of sublingual immunotherapy (SLIT) using Japa-nese cedar pollen extract for cypress pollinosis has been controversial. The 201-2-1 trial was the phase 3 study to clarify the efficacy of SLIT usingJapanese cedar pollen extract tablets for Japanese cedar pollinosis that had been conducted from 2015 to 2019. We analyzed the data of the 201-2-1trial to examine the efficacy of the tablets for Japanese cypress pollinosis. Method: The participants in the 201-2-1 trial who received placebo inthe first year (2015) were enrolled in this analysis. They were divided into the high responder group (“High,”N=108) and the low responder group(“Low,”N=131) to cypress pollen exposure based on the symptom scores during cypress pollen dispersal period. In the second year of the trial(2016), these subjects were randomly assigned to the active drug (PA) and the placebo (PP) groups. They were therefore divided into four groups:High-PA group (N=38), High-PP group (N=70), Low-PA group (N=43), and Low-PP group (N=88). We compared the mean total nasal symptommedication scores (TNSMS) in the peak of cypress pollen scattering period among these four groups in the second and third years. Results: Themean TNSMS of the PA group was significantly lower than that of the PP group. The occurrence of the adverse drug reactions (ADRs) was simi-lar among the“High”and“Low”group. Most of the ADRs were local reactions, and there was no increase in their intensity during the cypresspollen dispersal period. Conclusion: Japanese cedar pollen sublingual tablet effectively suppressed the clinical symptoms of Japanese cypress pol-linosis, and no additional safety concerns were identified.

PE30-5 Relationship between ocular and nasal symptoms in Japanese cedar pollinosis

Yukiyoshi Hyo1,2), Taro Saika1), Masakazu Hamamoto1), Ayaka Yokoyama1), Hirotaka Hara1) (Department of Otolaryngoglogy, Kawasaki MedicalSchool, Japan1); Hyo ENT Clinic, Japan2))

Objectives: Japanese cedar pollinosis causes high morbidity in Japan. Its nasal symptoms have been reported to cause various effects. Although italso causes ocular and dermal symptoms, there are only a few detailed reports on such symptoms. From this perspective, we investigated ocularsymptoms during the peak pollen-shedding periods from 2015 to 2019, each of which had a different number of airborne pollen grains. Methods:The investigation period covered the peak pollen-shedding period, which was defined as 2 weeks after the day when the number of airborne pol-len grains exceeded 100/cm2, from 2015 to 2019. Subjects were patients who met all the following criteria: (1) who presented to our hospital orother medical institutions involved in the study during the investigation period, (2) who were clinically diagnosed by an otorhinolaryngologist ashaving Japanese cedar pollinosis, (3) who had gone untreated during the current season, and (4) who filled out the Japanese Allergic ConjunctivalDisease Quality-of-Life Questionnaire (JACQLQ). This study was approved by the ethics committee of our hospital (approval 3010). Results: Theresults of the JACQLQ (containing five ocular symptom items) showed that 83% of the subjects had ocular symptoms. All symptoms occurredmost frequently in 2019, which had the highest number of airborne pollen grains. By symptom, itching occurred in 78.1% of subjects, foreign bodysensation in 53.6%, watery eyes in 51.0%, redness in 47.4%, and eye mucus in 32.9%. Most subjects experienced itching, and 7.23% experienced for-eign body sensation, watery eyes, redness, or eye mucus. Total nasal symptoms were correlated with total ocular symptoms; subjects with ocularsymptoms had worse nasal symptoms than those without. Although early-phase nasal symptoms such as watery, runny nose and sneezing werecorrelated with eye itching and redness, nasal congestion, a late-phase nasal symptom, was not correlated with any ocular symptoms. Conclusion:Japanese cedar pollinosis causes not only nasal symptoms but also ocular symptoms, which decrease quality of life. Therefore, we should under-stand that this disease is associated with systemic symptoms.

PE30-6 Knowledge, attitude and practices among patients and physicians on allergic rhinitis (KAPPA) study: Japan and Korea results

Sheila Chua1), Anup Pingle2), Jeanne M Pimenta3), Yoshitaka Okamoto4), Julie Pacer5), Jason Brinkley5) (Global, Classic & Established Products,GlaxoSmithKline, Philippines1); Global, Classic & Established Products, GlaxoSmithKline, India2); Respiratory Epidemiology, Value Evidence andOutcome, GlaxoSmithKline, UK3); Chiba University, Japan4); Abt. Associates, USA5))

Background: The objective of this study was to understand, compare attitudes, perceptions and current practices among allergic rhinitis (AR)patients and physicians. We present the results of KAPPA study from Japan and Korea. Method: We conducted a cross-sectional, multi-countrysurvey study of AR patients and physicians. Patients recruitment was via probability-based sampling method representing national and urbanpopulations, physicians were recruited from a high-quality physician online panel, representing national populations. Patient survey in Korea wasvia Computer-Assisted-Personal-Interview and self-administered online in Japan. Physician survey was self-administered online for both coun-tries. Results: A total of 400 patients and 424 physicians completed the survey. 60% of patients in Japan were males (mean age 48 years) while inKorea, 31% (mean age 44 years). Patients were largely from metropolitan (Japan 32%, Korea 96%) and suburban (Japan 27%, Korea 4%) areas withan educated/employed background. 21% of Japanese and 17% of Korean patients reported comorbid asthma. Physicians were from mixed metro-politan (Japan 25%, Korea 65%), suburban (Japan 23%, Korea 13%) and small city (Japan 37%, Korea 19%). Majority of patients reported AR sever-ity as moderate-severe (Japan 72%, Korea 80%) while majority of physicians (Japan 60%, Korea 80%) reported patients having mild AR. Both phy-sician (Japan 78%, Korea 83%) and patients (Japan 55%, Korea 71%) agreed that AR can be controlled with appropriate treatment. Among physi-cians, 58% from both countries though that patient preferred oral medications over intranasal corticosteroids (INCS) while 36% of Japanese and56% of Korean patients preferred oral medications over INCS. Safety concern was the most common cited barrier to INCS use by both patients(Japan 45%, Korea 32%) and physicians (Japan 55%, Korea 30%). Conclusion: In both countries, difference was noted in reported AR severity as-sessment and perception between patients and physicians. Compared to physicians, patients were less likely to agree that AR can be controlledand tend to underestimate the impact of uncontrolled AR. Safety concern was the most reported barrier to INCS use by both patients and physi-cians.

249

PosterSession

PE30-7 The relationship between hay fever symptoms and antibody titers of IgE, allergen-specific IgE, total IgE, and cross-reactive car-bohydrate determinant antigens in a company health examination

Hidenori Yokoi1), Yoshiyuki Takato2), Kiyomi Shinagawa2), Koichiro Saito1) (Department of Otolaryngology, Kyorin University, Japan1); SHIDAXResearch Institute, Japan2))

Background: In order to examine the effectiveness of allergen-specific IgE (sIgE) and total IgE (tIgE) antibodies in screening for hay fever in peo-ple exposed to pollen from the cedar, cypress, duckweed, and ragweed, we evaluated their hay fever symptoms and measured the titers of thesIgE and tIgE antibodies by compiling a questionnaire during a routine company health examination. Simultaneously, we also examined the effectof the cross-reactive carbohydrate determinant (CCD) antigen, which has been pointed out as one of the causes of false positives, in measuring thesIgE antibodies.Method: Among the participants in the company health examination, 132 responded with‘hay fever present’and 127 respondedwith‘hay fever absent’in the medical interview. The level of the sIgE antibody was measured using the AlaSTAT 3g Allergy method. Seven-teen components, including four types of CCD-specific IgE antibodies, were measured and evaluated comparatively. Results: A statistical analysisof the sensitivity and specificity of the correlation was used to predict the presence or absence of hay fever in the population tested. The values ofthe Area under the Curve (AUC) obtained from cedar-, cypress-, duckweed-, and ragweed-specific IgE antibody levels were 0.869, 0.821, 0.6245,and 0.555, respectively. The degree of association between the antigen-specific IgE levels and the status of the symptoms was in the order of ce-dar> cypress> duckweed> ragweed. The examination of the effect of CCD revealed that ragweed, wheat, and soybean have a greater CCD-related false positive effect in women. Conclusion: The employees of a company were evaluated for their hay fever symptoms and the titers oftheir serum IgE populations and CCD-specific antibodies were measured. The correlation between the symptoms and the antibodies was testedstatistically. A screening test using serum was shown to be the most useful one in examining cedar pollen. Women showed a greater chance of ob-taining false-positive results for ragweed in the CCD-antibody measurements.

PE30-8 Pollen sensitization pattern in patients with allergic diseases in the last 16 years in Mexico

Oscar I Moreno, Elsy M Navarrete, Blanca E Del Rio (Department of Allergy and Immunology Federico Gómez Mexico Children’s Hospital, Mex-ico)

Background: Pollen sensitization is involved in the pathogenesis of allergic diseases such as asthma and allergic rinitis. Climate change may alsoaffect the the release and atmospheric dispersion of pollen. The objective of the study was to analyze the changes in pollen sensitization in chil-dren in a Third-level Hospital in Mexico City during a period of 16 years and compare it with another studies in Mxico. Methods: Retrospectivestudy at Federico Gmez Mexico Children’s Hospital, of skin prick tests results to tree, weed and grass pollen performed from January 2004 to De-cember 2019. Patients aged 2-18 years who presented an allergic disease and who had immediate hypersensitivity skin prick test to pollens, theresults were compared with previous reports from another institutions. Descriptive analysis and x2 statistics were used. Results: A total of 11,618patients were included, 88.8% had skin prick tests positive at least one pollen (95% CI 88.7-88.9). The most frequently positive pollen was: Fraxinus17.8% (CI 17.7-17.9), and the lowest Rumex 10.5% (CI 10.4-10.6). The frequency of sensitization was much higher in patients aged 6-12 years oldcompared to the group of patients under 6 years old (p＝0.000), there was no difference in patients older than 12 years old. In general, the sensiti-zation percentage remained stable in recent years. There was a decrease in the percentage of pollen sensitization from 2008 to 2013, compared toprevious years. Conclusion: The pollen sensitization frequency is much higher from aged 6-12 years. In general, the sensitization percentage re-mained stable in recent years, however, a decreasing pattern was observed from 2008 to 2013 and then ascending pattern, probably due to envi-ronmental conditions.

PE30-10 The treatment results of selective resection of the posterior nasal nerve for intractable allergic rhinitis

Yusuke Suzuki1), Yasuhiro Abe1), Kazuya Kurakami1), Yui Kawai1), Chihiro Watanabe1), Yusuke Nouchi1), Takashi Asano1), Nobuo Ohta2),Seiji Kakehata1) (Department of Otolaryngology, Yamagata University, Japan1); Division of Otolaryngology, Tohoku Medical and PharmaceuticalUniversity, Japan2))

Purpose of the Study: Posterior nasal neurectomy (PNN) is the surgical procedure for intractable allergic rhinitis (AR). Recently, selective resec-tion of the posterior nasal nerve (SRPN) has been reported. In this procedure, the peripheral branches of the posterior nasal nerve ware resectedat the level of submucosa of the inferior turbinate. The aim of this study was to assess the therapeutic effects of SRPN in AR patients. Materialsand Methods Used: Sixty six patients with AR underwent SRPN between December 2015 and December 2019. Subjective outcomes were repre-sented by symptom scores and olfactometric technique by the use of olfactometer. Objective outcomes were represented by serelogical examina-tion and rhinomanometry. Both subjective and objective assessments were performed before surgery and 6 months after surgery. Results: Allsymptoms improved postoperatively with significant difference. The level of total IgE in the serum decreased, and the score of olfactometric tech-nique and rhinomanometry improved postoperatively with significant difference. Conclusion: It was contemplated that SRPN was a useful and ef-ficient procedure for patients with AR. However, longer follow-up studies are required in order to validate our study.

250

PosterSession

PE30-11 Clinical characteristics of Japanese patients with physician-diagnosed allergic rhinitis in the JMDC claims database

Hajime Yoshisue1), Chie Ito2), Mitsuhiro Okano3) (Medical Division, Novartis Pharma K.K., Japan1); JMDC Co. Ltd., Japan2); Department of Otorhino-laryngology, International University of Health and Welfare School of Medicine, Japan3))

Background: The prevalence of allergic rhinitis (AR) has been increasing in Japan. While AR is considered as a national affliction in Japan, evi-dence of the clinical patients’ profile in a real-life setting is scarce. We utilized commercially available insurance claims database to investigateclinical characteristics of Japanese patients with AR. Methods: This is a non-interventional, retrospective study examining patients withphysician-diagnosed AR in Japan using a Japan Medical Data Center (JMDC) claim database. The study period is January 2009 to December 2018(10 years). For primary objective, patients with 2 AR diagnoses (ICD-10, J30) in the year and 2 years old were characterized in this study (primarycohort). For secondary objectives, primary cohort was divided into surgery cohort and non-surgery cohort, and severe non-surgery cohort wasextracted with 2 controllers. The AR-related surgeries (e.g., turbinectomy) were defined by Japanese guidelines for AR. These cohorts wereevaluated about clinical characteristics by each year. To compare the 1-year pre-index (surgery or second AR diagnosis) clinical characteristics,health care resource utilization (HCRU) and seasonality for surgery and severe non-surgery cohorts, severe non-surgery cohort was matched tothe surgery cohort using age, sex and insurance status by each year. Results: For primary cohort, in 2018, out of total 879,348 patients included inthe study, 447,376 (50.9%) were male. Mean (SD) age of patients was 30.7 (20.52). A total of 258,855 patients were included in severe non-surgery co-hort in 2018. For comparison cohorts, while chronic rhinosinusitis was higher (49.8%) in surgery vs severe non-surgery (29.7%), asthma (40.5% vs29.7%) and allergic conjunctivitis (52.4% and 38.9%) were higher in severe non-surgery vs surgery. Seasonal trend for HCRU and prescriptionswas observed; AR-related surgeries had peak from December and January, while AR-related prescription had peak in March. Conclusion: De-spite several limitations due to the nature of a database study, this is, to our knowledge, the first study using a large-scale claims database examin-ing clinical characteristics of Japanese patients with AR including those with or without AR-related surgeries.

PE30-13 Efficacy of sublingual immunotherapy for Japanese cedar pollinosis allergic rhinitis in children

Shohei Tanaka1), Kayoko Kawashima1), Masashi Yamamoto1), Mika Okuno1), Toshinobu Nakatake2), Yuki Tsurinaga2), Yohei Hukazawa2),Tamana Nakano2), Amane Shigekawa2), Yuri Takaoka2), Yukinori Yoshida2), Makoto Kameda2) (Department of Otorhinolaryngology, OsakaHabikino Medical Center, Osaka Prefectural Hospital Organization, Japan1); Department of Pediatrics, Osaka Habikino Medical Center, Osaka Pre-fectural Hospital Organization, Japan2))

Background: The pediatric patients with japanese cedar (JC) pollinosis has a tendency to increase. Sublingual immunotherapy (SLIT), which isexpected as the only radical therapy, was approved as a treatment for pediatric allergic rhinitis in children under 12 years old in Japan in 2018and 2 years has passed after we started JC pollen SLIT for the pediatric patient with JC pollinosis in 2018. The purpose of this study is to clear theefficacy of JC pollen SLIT for seasonal allergic rhinitis induced by JC pollinosis. Methods: (1) We studied patients with JC pollinosis 15 years andunder, who were started on JC pollen SLIT in 2018 (JC pollen SLIT from 2018 group). The efficacy was evaluated with symptom scores and qual-ity of life (QOL) scores by the Japanese Allergic Rhinitis Standard Quality of Life Questionnaire (JRQLQ No1) during the JC pollen season in 2019and 2020. (2) The efficacy during the JC pollen season in 2020 was compared between JC pollen SLIT from 2018 group, JC pollen SLIT from 2019group and pharmacotherapy (without SLIT) group. The efficacy was evaluated with symptom scores and quality of life (QOL) scores by the Japa-nese Allergic Rhinitis Standard Quality of Life Questionnaire (JRQLQ No1). Results: (1) The symptom scores and QOL scores in 2020 had a ten-dency to be lower than in 2019. (2) The symptom scores and QOL scores of JC pollen SLIT from 2018 group and JC pollen SLIT from 2019 grouphad a tendency to be lower than those of pharmacotherapy group. Conclusion: This study shows that JC pollen SLIT in children is expected tohave therapeutic effect over the years. On the other hand, we need to take the low airborne JC pollen levels and the impact of COVID-19 in 2020into consideration.

251

PosterSession

Poster Session 31Rhinosinusitis

PE31-1 Nasal therapies affect the levels of allergic shiners in children with allergic rhinitis

Cheng-Tsung Yang1,2), Bor-Luen Chiang2,3,4) (Department of Pediatrics, Camillian Saint Mary’s Hospital Luodong, Taiwan1); Graduate Institute ofClinical Medicine, College of Medicine, National Taiwan University, Taiwan2); Department of Pediatrics, National Taiwan University Children’sHospital, Taiwan3); Department of Medical Research, National Taiwan University Hospital, Taiwan4))

Background: The correlation between the color and size of allergic shiners and the severity of allergic rhinitis was documented in 2009. But therewas no data revealing the reduction of allergic shiners after the relief of allergic rhinitis. This study aims that comparison of the effectiveness oftreatments for alleviating allergic shiners in children with allergic rhinitis. Method: One hundred and fifty children aged from 6 years old to 12years old with moderate-severe allergic rhinitis will be randomly assigned into three groups, and have treatments with oral antihistamine, com-bined nasal corticosteroids (NCS) and oral antihistamine, and combined NCS and oral antihistamine plus nasal decongestant (ND) in control group,group 1, and group 2, respectively. A standardized digital photograph and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire(PRQLQ) will be finished at the beginning of the treatment, and on the 7th day, 14th day, and 28th day after treatment. The study was approvedby the Ethics Committee of Camillian Saint Mary’s Hospital Luodong. Results: The preliminary results suggested that all participants got im-provement of allergic rhinitis and allergic shiners, and it seemed to be more effective on alleviating allergic shiners by combined NCS and oral an-tihistamine treatment compared to oral antihistamine only (p=0.071). The alleviation of average of darkness of shiners was associated with the im-provement of PRQLQ score (p=0.051) after treatment of allergic rhinitis. More complete results will be finished and analyzed. Conclusion: Our in-itial results indicated that combined NCS and oral antihistamine seemed to be effective to alleviate allergic shiners in children with allergic rhini-tis. More results will be analyzed and reported then.

PE31-3 Upper airway cough syndrome (UACS) in children with chronic cough

Momoko Sakurai1), Natsuko Masumoto1), Rieko Higashijima1), Yoshito Ishizaki1), Junichiro Tezuka2) (Department of Pediatrics, National Hospital Or-ganization Fukuokahigashi Medical Center, Japan1); Department of Allergy and Pulmonology, Fukuoka Children’s Hospital, Japan2))

Background: Chronic cough derived from either bronchial asthma or UACS (also referred to as rhinosinusitis and rhinitis) is often observed inchildren. In the present study, we report 6 cases of children diagnosed with UACS who have chronic cough and improvements in asthma treat-ment. Cases: A total of 6 children, who were with findings of chronic rhinosinusitis following sinus X-ray examinations at Department of Pediat-rics, National Hospital Organization Fukuokahigashi Medical Center between April 2019 and March 2020, were included in the present study. Thepatients’ characteristics were the following: (1) male: female ratio=1:1; (2) median age=9 years (5-15 years); (3) median serum total IgE (IU/ml)=90.9(5-538); (4) subjects with allergic rhinitis=3; and (5) subjects with asthma complications=5. While bronchodilators and expectorants were adminis-tered to all children, steroid inhalers and antihistamines were provided to 4 and 5 subjects, respectively. Given that an absence of improvementsin patients’ coughs was observed following these treatments, macrolide antibiotics were administered. However, these improved the conditions of3 children only. In contrast, 2 children benefitted from either ABPC/SBT and CDTR-PI therapy, 2 children benefitted from intranasal glucocorti-coids. Conclusion:We suggest UACS to be an important cause of chronic cough and therefore, it should be treated and appropriately managed.Furthermore, we propose coordination with otolaryngologists to be warranted in such cases.

PE31-4 Objective evaluation of the deviation of nasal septum and selection of surgical techniques

Shogo Kimura, Yuji Nakamaru, Masanobu Suzuki, Aya Honma, Akira Nakazono, Akihiro Homma (Department of Otolaryngology-Head & NeckSurgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan)

Background: Most of patients with allergic rhinitis (AR) represent nasal obstruction. Not only swollen nasal mucosa due to allergic response inthe nasal cavity but also deviation of nasal septum, especially caudal deviation, worsen the symptom. So far, several methods were reported tocorrect caudal deviation of nasal septum, including Open Septorhinoplasty (OSR) and Killian incision (KI). However, little evidences were shownon the effect of OSR and KI for the caudal deviation in an objective manner.Methods:We retrospectively analyzed about 18 patients who under-went OSR and 11 patients who underwent traditional septoplasty with KI from June 2007 to October 2019. Caudal deviation was defined on thedistance between anterior nasal spine (ANS) and most deviated point (MDP) in nasal septum on computerized tomography. The deformation rate(DR) of nasal septum was also calculated. Nasal airway resistance and visual analogue scale (VAS) score of nasal obstruction were examined. Re-sults: The distance between ANS and MDP was significantly correlated the VAS score (r=-0.58, p=0.017). The deformation rate in patients withcaudal septal deviation were significantly decreased with OSR (0.14±0.06 to 0.03±0.03, p=0.004), while not with KI (0.09±0.08 to 0.04±0.03, p=0.25). OSR also improved nasal airway resistance (1.10±0.44 to 0.42±0.15, p=0.02), and the VAS score (79.11±14.74 to 5.78±7.89, p=0.004). Conclu-sion: Nasal obstruction is more severe in patients with the caudal deviation. OSR significantly correct the caudal deviation of nasal septum thanKI. The two parameters, the distance from ANS to MDP and the DR value, could be useful to evaluate the deviation of nasal septum. We could se-lect the surgical technique by those evaluation of nasal septum.

252

PosterSession

PE31-5 Benralizumab for eosinophilic sinusitis or otitis media complicated with bronchial asthma

Taro Saika, Yukiyoshi Hyo, Ayaka Yokoyama, Masakazu Hamamoto, Hirotaka Hara (Kawasaki Medical School, Japan)

Objective: Benralizumab has been used as a therapeutic agent for bronchial asthma (BA). In the present study, we examined the efficacy of ben-ralizumab in the treatment of an eosinophilic inflammation of the upper airways. Methods: Benralizumab was administered to 5 patients witheosinophilic chronic sinusitis (ECRS) or eosinophilic otitis media (EOM) complicated with BA to control both conditions. Serum IgE, fractional ex-haled nitric oxide (FeNO), and the CT score were evaluated before and after treatment of benralizumab, and the baseline and post-treatment val-ues were compared. Results: Serum IgE levels and FeNO levels were elevated in 3 patients before treatment but in only 2 patients after treat-ment. In the 2 patients whose baseline serum IgE levels were normal. Of the 4 patients who did not have EOM, only one showed an improved CTscore. Discussion: Benralizumab appears to have limited efficacy in treating eosinophilic inflammation of the upper airways.

PE31-6 Local zinc depletion promotes cytokine secretion and infiltration of inflammatory cells in nasal mucosa

Masanobu Suzuki1), Yuji Nakamaru1), Mahnaz Ramezanpour2), Takayoshi Suzuki1), Aya Honma1), Akira Nakazono1), Shogo Kimura1),Peter-John Wormald2), Sarah Vreugde2), Akihiro Homma1) (Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine andGraduate School of Medicine, Hokkaido University, Japan1); Department of Surgery Otorhinolaryngology Head and Neck Surgery, the QueenElizabeth Hospital, and the University of Adelaide, Australia2))

Introduction: Zinc is critically important in many biological processes and altered homeostasis of intracellular zinc causes inflammatory condition.Severe or marginal zinc deficiency were documented in many allergic inflammatory diseases, such as bronchial asthma and atopic dermatitis. Re-cently, low zinc levels in nasal mucosa from chronic rhinosinusitis (CRS) were reported, although the significance in the pathogenesis of CRS is stillunknown. We assessed the effect of zinc depletion on cytokine secretion by primary human nasal epithelial cells (pHNECs) and examined the rela-tionship between local zinc levels and infiltrating cells in nasal mucosa. Material and Methods: pHNECs were obtained from the nasal mucosaand incubated in zinc-depleted media, followed by ELISA to IL-6 and IL-8. Mucosal zinc levels and infiltrating cells were evaluated with Zinquinand HE stain respectively, using tissue micro arrays (TMA) containing nasal mucosa of non-CRS controls, CRS without and with nasal polyps(CRSsNP and CRSwNP). Results: IL-6 and IL-8 secretion were significantly increased in pHNECs cultivated in zinc-depleted media (IL-6; p=0.01and IL-8; p=0.04). TMA assays showed mucosal zinc levels were significantly decreased with eosinophils and all inflammatory cells increased innasal mucosa of CRSwNP patients. There was significant negative correlation between zinc levels and eosinophils and all infiltrating cells in nasalmucosa (zinc and eosinophils; r=-0.40, p=0.03, zinc and all infiltrating cells; r=-0.49, p<0.01). Conclusion: Local zinc depletion in nasal mucosa couldbe involved in the pathogenesis of nasal polyps through promoting proinflammatory cytokine secretion and eosinophil infiltration into nasal mu-cosa.

PE31-8 Successful management of eosinophilic chronic rhinosinusitis complicated by severe asthma using dupilumab, following nega-tive initial results with benralizumab

Isao Suzaki1), Akihiko Tanaka2), Kojiro Hirano1), Sawa Kamimura1), Yuki Maruyama1), Yoichiro Narikawa1), Eriko Sekino1), Hitome Kobayashi1) (De-partment of Otorhinolaryngology, School of Medicine, Showa University, Japan1); Department of Medicine, Division of Respiratory Medicine andAllergology, Showa University, School of Medicine, Japan2))

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of refractory chronic rhinosinusitis (CRS) characterized by ethmoid-predominant sinusitis with eosinophilic infiltration, and frequent complicated by asthma. Although appropriate endoscopic sinus surgery andpost-operative management including comprehensive management for upper and lower airway inflammation, as with united airway disease, arenecessary, there are currently no well-established treatments for this condition. An anti-IL-4Rα monoclonal antibody, dupilumab, was approvedfor the treatment of atopic dermatitis, severe asthma and refractory CRS with nasal polyps (CRSwNPs). Methods: We evaluated the clinicalcourse of asthma and nasal condition before and after biologics treatment. Results: At first, benralizumab, anti-IL-5Rα monoclonal antibody, wasinitiated for a 49-year-old male who had severe eosinophilic asthma and a recurrence of eosinophilic chronic rhinosinusitis. Although blood eosino-phils and number of infiltrated eosinophils in the nasal polyps were significantly reduced, it did not improve his asthma and nasal symptoms, en-doscopic findings and sinus computed tomography (CT) scan. As the result of the negative response of anti-IL-5 therapy, we judged that benrali-zumab was not effective on his asthma and ECRS conditions. At 4 months after the initiation of benralizumab, we changed the biologics from ben-ralizumab to dupilumab to broadly suppress type 2 inflammation. After the initiation of dupilumab, his nasal and asthma symptoms, endoscopicfindings and sinus CT scan showed great improvement. Additionally, he did not need oral corticosteroids treatment for maintaining his asthmaand ECRS condition while receiving dupilumab. Conclusion: This is the first case report that dupilumab showed the great clinical effect on ECRScomplicated by severe asthma, following negative response of benralizumab. Biologics are expected to be an epoch-making treatment choice forrefractory airway inflammatory disease such as asthma and ECRS.

253

PosterSession

PE31-11 Immuno-histological analysis of sinusitis tissue from the cases who were not fully improved after anti-IL-5 therapy

Kazuyuki Chibana1), Taichi Shiobara1), Yukiko Horigane1), Yusuke Nakamura1), Ryo Arai1), Akihiro Takemasa1), Yasuo Shimizu1), Shinichi Haruna2),Seiji Niho1) (Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Japan1); Department of Otorhi-nolaryngology, Dokkyo University School of Medicine, Japan2))

Background: It was reported that complication with eosinophilic sinusitis was 66.3% in severe asthma subjects. As well, complication withasthma in eosinophilic sinusitis was 41.6%. The incidence of complication of asthma and eosinophilic sinusitis is quite high. In Japanese guideline2018, as treatment for step IV, biologic agents would be recommended for severe asthma who was prescribed high dose ICS, LABA and LAMA.As of October 2019, four biologic agents were able to administer to asthma patients in Japan. In this presentation, we describe as“anti-IL-5 ther-apy”including, mepolizumab and benralizumab. It was expected that“anti-IL-5 therapy”is effective for eosinophilic sinusitis because of its pow-erful suppressive effects for eosinophils. However, we sometimes experience the cases who were not fully improved their sinusitis by“anti-IL-5therapy”in clinical situations.Methods: Twenty-six subjects were administrated“anti-IL-5 therapy”in our department for now. Though five pa-tients of those showed validity in asthma symptoms, the sinusitis manifestation including congestion and olfactory reduction were not fully im-proved. Furthermore, 2 of 5 patients were operated in department of otorhinolaryngology and were comparable with sinusitis tissue before andafter“anti-IL-5 therapy”. We conducted HEstain, PAS stain and Hansel stain histologically for these samples. We also performed immuno-histchemistry staining for CD4, CD8, IgG4, neutrophil elastase, periostin, eosinophil granule protein and DPP4. Results: After“anti-IL-5 therapy”,eosinophils and eosinophil granule protein completely disappeared from sinus tissue. On the contrary, CD4-positive cells were increased in the si-nus tissue, although CD8 and IgG4-positive cells were not altered. Periostin and DPP4 positive cells did not have any changes in approximatelywith“anti-IL-5 therapy”. Neutrophil elastase disappeared in sinus tissue. Conclusion: We experienced the subjects who were clearly decreasedeosinophils from sinus tissue by“anti-IL-5 therapy”, however their sinusitis symptoms were not fully improved. It was suggested that“anti-IL-5therapy”might not control type2 inflammation completely. Interestingly, neutrophils also disappeared in sinus tissue, it was suggested that“anti-IL-5 therapy”might influence granulocytes.

PE31-12 Plasma galectin-10 levels and mucosal eosinophil infiltration in chronic rhinosinusitis

Takechiyo Yamada1), Yui Miyabe1), Hidekazu Saito1), Shigeharu Fujieda2), Shigeharu Ueki3) (Department of Otorhinolaryngology, Head and NeckSurgery, Akita University, Japan1); Department of Otorhinolaryngology-Head and Neck Surgery, University of Fukui, Japan2); Department of Gen-eral Internal Medicine and Clinical Laboratory Medicine, Akita University, Japan3))

The Charcot-Leyden crystal (CLC) protein, galectin-10 is a predominant protein present within the cytoplasm of eosinophils. In order to identifyplasma biomarker for local eosinophil infiltration in refractory rhinosinusitis, we have measured the levels of molecules including galectin-10 in theplasma of patients and compared the number of infiltrating eosinophils in nasal mucosa. Mucosal tissues from 97 patients with chronic rhinosinusi-tis were obtained from the nasal polyps during surgery. Blood samples were obtained and the levels of molecules were measured using ELISA ormultiple assay systems according to the manufacturers’ protocols. The groups were divided into two groups, according to the levels of infiltratingeosinophil or molecules. The plasma level of galectin-10 was significantly higher in the high-eosinophil mucosal infiltration group (p<0.005). Thenumber of infiltrating eosinophils in the mucosa was significantly higher in the group with the higher galectin-10 level (p<0.05). The levels of IP-10,eotaxin-2, and eotaxin-3 were significantly higher in the high-level galectin-10 group. This is the first report suggesting galectin-10 as a plasmabiomarker for mucosal eosinophil infiltration.

PE31-13 Investigation about sensitization rate of inhalable antigens in Hirosaki city for 10years

Junko Takahata, Atsushi Matsubara (Department of Otorhinolaryngology, Hirosaki University, Japan)

Background: Allergic rhinitis has tend to increase in Japan. In Iwaki area of Hirosaki city, we have investigated about various things to seek theway people can live longer. As part of that, sensitization rate of inhalable antigens has been investigated in 2008～2018. Methods: Subjects areresidents of Iwaki area, who want to participate this project. Every year, about 1000 people participate this project, and we investigated specificIgE antibody of cedar pollen, housedust1, poaceous pollen, and weed pollen by Immuno CAP. Sensitization rate was also investigated by genderand age. Results: Sensitization rate of all antigens has increased significantly. Especially, cedar pollen sensitization rate has increased remarkably(31.0% in 2008, 47.2% in 2018). Regardless of gender, sensitization rate of cedar pollen is high from 20’s to 50’s. The reason is considered that cedarpollen scatters increasingly in Hirosaki. It is guessed that housedust is gaining in our warm housing environment. Women seemed to sensitizenewly after middle ages, but men tended not to sensitize newly after middle ages except ceder pollen. Conclusion: It is suggested that allergicrhinitis has still increased. Sensitization rate is different among gender and age.

254

PosterSession

PE31-14 Investigation of the effect of benralizumab for chronic rhinosinusitis with nasal polyps

Masashi Yamamoto1), Kayoko Kawashima1), Mika Okuno1), Seijirou Minamoto2), Osamu Matsuno2) (Department of Otorhinolaryngology, OsakaHabikino Medical Center, Japan1); Department of Allergy, Osaka Habikino Medical Center, Japan2))

Background: Benralizumab is a humanized anti-IL-5 receptor α mAb that depletes eosinophils and be used for uncontrolled severe eosinophilicasthma. Eosinophilic type2 inflammation, which is induced by IL-5, IL-25 and IL-33, has a key role in the pathogenesis of severe eosinophilicasthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Here we report a series of 9 cases of severe eosinophilic asthma patients withCRSwNP. Methods: A 1-year, prospective observantional study from March 2018 to September 2018. Patients are received 30mg benralizumabevery 4 weeks in first 3 months and every eight weeks after that. Computed tomogramphy (CT) sinuses, nasal endoscopy, VAS (visual analogscale) for sino-nasal symptoms severity, blood eosinophil count and nasal discharge eosinophil count are routinely performed. Result: 3 patientshave undergone ESS (Endoscopic Sinus Surgery) and had a recurrence and mepolizumab had been administered before benralizumab to 2 pa-tients. In 7 patients, CT Lund-Mackay score decreased in the 1 year. On the other hand, 2 patients underwent FESS (Functional Endoscopic SinusSurgery) 1 year after observation. Conclusion: Benralizumab improved NP in patients with uncontrolled severe eosinophilic asthma withCRSwNP.

PE31-15 Epidemiological study of allergic diseases, symptoms, and quality of life in school children

Ayaka Yokoyama, Yukiyoshi Hyo, Taro Saika, Masakazu Hamamoto, Hirotaka Hara (Department of Otolaryngology, Kawasaki Medical School,Japan)

Background: An epidemiological study was conducted to investigate the relationship between allergic disease and quality of life (QOL) in schoolchildren. Methods: Since 2017, we have conducted epidemiological surveys of allergic diseases in children under 12 years old in Asakuchi-gun,Satosho-cho, Okayama Prefecture. We investigated the prevalence of allergic diseases and the effects of allergic symptoms on QOL among 2nd to6th graders through a questionnaire distributed at school and completed with parents at home. We used a questionnaire that assessed the pres-ence or absence and symptoms of allergic diseases, the Japanese Allergic Conjunctival Disease Quality-of-Life Questionnaire, and the pediatricsleep respiratory disorder QOL survey table, OSA-18. Results: In total 305 questionnaires were completed, a response rate of 58.2%. The 305 ques-tionnaires covered 185 boys and 147 girls. The prevalence of disease was 59.6% for allergic rhinitis (the highest), 14.7% for atopic dermatitis, and10.8% for bronchial asthma. The incidence of allergic diseases was higher in higher grades than in lower grades. Nasal congestion was the mostcommon nasal symptom, and itchy eyes dominated eye symptoms. Ten cases (3.0%) scored 51 points in the OSA-18. OSA-18 scores were higher inchildren with allergic disease than in those without. Conclusion: School children with allergic diseases had higher OSA-18 scores. Our earlierwork found that the incidence of allergic rhinitis on QOL was weak in childhood. It is possible that allergic rhinitis has a greater effect on QOLduring school age. The prevalence of allergic disease was high, suggesting that it reduces QOL.

PE31-16 Prevalence of sleep disorders in children with allergic rinitis

Maria Del Carmen Zarate Hernandez, Sandra N González-Díaz, Genhssy K Rocha, Argentina Rodriguez, Maria Del Rocio Salinas, Diana M Rangel(Regional Center of Allergy and Clinical Immunology, Mexico)

Background: Allergic rhinitis has a global prevalence of 40%, approximately 88% of children with allergic rhinitis have sleep problems. The objec-tive of this study is to identify the prevalence of sleep disorders in children with allergic rhinitis. Methods: observational, cross-sectional study,which included children from 6 to 10 years old, with allergic rhinitis who attended the Regional Center of Allergy and Clinical Immunology of theHospital Universitario Dr Jos Eleuterio Gonzlez from February 2017 to September 2018 with sensitization to aeroallergens, which they do not re-ceive immunotherapy. Two questionnaires were completed: 1) Children’s Sleep Habits Questionnaire (CSHQ) answered by the caregiver and 2)Pediatric and Adolescent Rhinoconjunctivitis Quality Of Life Questionnaire (PRQLQ) answered by the child. Children with neurodevelopmentaldelay, anatomic facial alteration, use of neuroleptics, infectious process of the upper respiratory tract were excluded. Results: 66 patients were in-cluded, 42.4% with intermittent mild allergic rhinitis. 68.2% of tutors did not consider that their child’s sleep was affected by allergic rhinitis, 77.3%rarely complain of sleep problems. The mean in the CSHQ questionnaire was 48.28 +/- 8.13; 77% were considered positive for sleep disorders. Themedian in the PRQLQ questionnaire was 2.17 +/- 1,007, which corresponds to a moderate quality of life condition. Children with mild intermittentallergic rhinitis had the lowest average score (1.75 +/- 0.95) and the highest score was in children with moderate intermittent allergic rhinitis (2.92+/- 0.14), this difference was statistically significant (p=0.021). No statistically significant correlation was found between quality of life and the pres-ence of sleep disorders. Conclusion: the most children with allergic rhinitis have sleep disorders, however, there may be underestimation ofsymptoms by caregivers, it is important to detect at the first consultation as they can be associated with decreased school performance and qual-ity of life.

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PosterSession

PE31-17 Impact of eosinophilic status on efficacy of dupilumab in the JESREC subpopulations of phase 3 SINUS-52 study for severechronic rhinosinusitis with nasal polyps

Shigeharu Fujieda1), Shoji Matsune2), Sachio Takeno3), Nobuo Ohta4), Mikiya Asako5), Claus Bachert6,7), Martin Desrosiers8), Tomoyuki Inoue9),Yoshinori Takahashi9), Hiroyuki Fujita9), Benjamin Ortiz10), Yongtao Li11), Nikhil Amin10), Leda P Mannent12) (Department of OtorhinolaryngologyUniversity of Fukui, Japan1); Nippon Medical School, Japan2); Hiroshima University Hospital, Japan3); Tohoku Medical and Pharmaceutical Univer-sity, Japan4); Department of Otorhinolaryngology, Kansai Medical University, Japan5); Ghent University, Belgium6); Karolinska Institutet, Swe-den7); CRCHUM, Canada8); Sanofi K.K., Japan9); Regeneron Pharmaceuticals, Inc., USA10); Sanofi U.S., USA11); Sanofi France, France12))

Background: Dupilumab is a fully human monoclonal antibody which blocks the shared receptor component for IL-4 and IL-13, key and central driv-ers of type 2 inflammation. In the phase 3 SINUS-52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP)on a background of mometasone furoate (n=448) despite prior treatment with systemic corticosteroids and/or surgery, dupilumab demonstrated im-proved endoscopic, radiologic, clinical and patient-reported sinonasal outcomes. We assessed impact of eosinophilic status of patients with severeCRSwNP on efficacy of dupilumab in the JESREC (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis) subpopula-tions in the SINUS-52 Study. Method: In SINUS-52, patients were randomized 1:1:1 to dupilumab 300mg q2w until week 52 (Arm A; n=150), dupi-lumab 300mg/q2w until week-24 followed by 300mg/q4w until week-52 (Arm B; n=145), or placebo matching until week 52 (Arm C; n=153). Co-primary efficacy endpoints were change from baseline in nasal polyp score (NPS), nasal congestion (NC) score and Lund-Mackay score assessed byCT scan (LMK-CT) in the pooled arms A and B at Week-24. In this post-hoc analysis, patients were stratified by eosinophilic chronic rhinosinusitis(ECRS) status at baseline as non ECRS (n=73), mild ECRS (n=61), moderate ECRS (n=144), and severe ECRS (n=160) according to the JESREC diag-nostic algorithm. Results: At baseline, patients tended to have more severe disease characteristics with increasing ECRS severity. Pooled dupilumab300 mg/q2w demonstrated comparable efficacy in co-primary endpoints of NPS, NC, LMK-CT at Week-24 through each subgroup classified by JES-REC algorithm. Comparable efficacy profiles were also observed for dupilumab compared with placebo in patients with CRSwNP among each JES-REC subpopulation in all key secondary endpoints (total symptom score, UPSIT, SNOT-22, and VAS for rhinosinusitis). Dupilumab was well toler-ated. Conclusion: Compared with placebo, dupilumab provided rapid improvements in co-primary and key secondary endpoints with a safety profileconsistent with the overall population of patients with CRSwNP recruited to the SINUS-52 study. Improvements were seen in all ECRS groups.

PE31-18 Baseline characteristics of patients with CRSwNP with asthma and dupilumab efficacy by baseline biomarker level: results fromthe SINUS-24 and SINUS-52 phase 3 trials

Mikiya Asako1), Shigeharu Fujieda2), Yoshiki Kobayashi1), Jorge F Maspero3), Joaquim Mullol4), Claus Bachert5,6), Martin Desrosiers7), Mei Zhang8),Xuezou Mao8), Nikhil Amin9), Leda P Mannent10) (Department of Otorhinolaryngology, Kansai Medical University, Japan1); University of Fukui, Ja-pan2); Fundación CIDEA, Argentina3); Universitat de Barcelona, Spain4); Ghent University, Belgium5); Karolinska Institutet, Sweden6); CRCHUM,Canada7); Sanofi U.S., USA8); Regeneron Pharmaceuticals, Inc, USA9); Sanofi France, France10))

Background: Dupilumab blocks the shared receptor component of interleukin-4 and interleukin-13, key and central drivers of type 2 inflamma-tion in multiple diseases. We report baseline disease characteristics and effect of dupilumab on upper and lower airway outcomes in patients withCRSwNP and comorbid asthma from the pooled populations of the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies, cate-gorized by baseline serum total IgE and TARC levels. Methods: SINUS-24 participants were randomized 1:1 to 24 weeks of subcutaneous dupi-lumab 300mg or placebo q2w, and SINUS-52 participants, 1:1:1 to subcutaneous dupilumab 300mg q2w for 52 weeks, dupilumab 300mg q2w for 24weeks then q4w for 28 weeks, or placebo q2w for 52 weeks. Dupilumab was evaluated (pooled q2w) vs placebo in the intention-to-treat populationwith asthma categorized by baseline median values of serum total IgE (120 IU/mL) and TARC (291 pg/mL). Results: Of 724 patients, 428 (59.1%)had comorbid asthma. Baseline CRSwNP disease characteristics were comparable between patients with/without asthma, but IgE and TARClevels were higher in asthma patients. Baseline upper and lower airway disease characteristics were similar for patients with baseline IgE120/<120 IU/ml and TARC291/<291 pg/mL. Baseline mean (SD) disease characteristics scores were: NPS 6.0 (1.3); NC 2.4 (0.6); LMK-CT 19.1 (3.8);SNOT-22 54.0 (20.2); CRS severity by VAS 8.0 (2.0); UPSIT 12.4 (7.0); loss of smell 2.9 (0.5); PNIF 87.0 (57.3) L/minute; ACQ-6 1.6 (1.1); FEV1 2.6 (0.9) L.Most patients were in GINA step 3 or 4 by baseline asthma medication. Mean (SD) IgE and TARC values at baseline were 249.1 (308.8) IU/mL and377.4 (266.1) pg/mL, respectively. At Wk24, NPS, NC score, PNIF, ACQ-6 and FEV1 improved in patients receiving dupilumab regardless of base-line IgE and TARC levels (all P<0.01 vs placebo). Conclusion: In patients with CRSwNP with comorbid asthma in SINUS-24 and SINUS-52, base-line upper and lower airway disease characteristics were similar regardless of baseline serum total IgE or TARC levels. Dupilumab improvedthese disease characteristics regardless of baseline IgE or TARC levels.

PE31-19 A retrospective study on the safety of Japanese cedar pollen and house dust mite sublingual immunotherapy in children withmultiple allergies

Hiroshi Kitazawa, Yukari Ichikawa, Shuhei Oba, Eiichiro Kawai, Naomi Hino-Fukuyo, Tetsuji Morimoto (Division of Pediatrics, Faculty of Medi-cine, Tohoku Medical and Pharmaceutical University, Japan)

Sublingual immunotherapy (SLIT) is expected to be an effective treatment for pediatric rhinosinusitis. SLIT tablets for Japanese Cedar pollen (JC)and house dust mite (HDM) are available in Japan and the safety of these tablets has already been reported in children strictly selected in a re-search context. In the present study, we aimed to confirm the safety of SLIT in outpatient children with multiple allergic diseases visiting the De-partment of Pediatric Allergy, thus in a“real clinical”context of a relatively high-risk population for allergic reactions. We examined the safetyand tolerability of SLIT introduction through a retrospective review of the medical records of all patients treated with any SLIT, including pa-tients’ allergic comorbidities, serum total IgE levels, SLIT related adverse events (AEs) and use of antihistaminic agents. Among the 26 patientsundergoing SLIT, 4 were treated with single JC, 12 with single HDM and 10 with both allergens (Dual SLIT). The median serum total IgE level atthe introduction of SLIT was 661 IU/mL (70.6 3170 IU/mL) for JC and 1076.5 IU/mL (148 3190 IU/mL) for HDM. History of eczema, bronchialasthma, food allergy and sensitization to other aeroallergens was seen respectively in 62%, 42%, 35% and 88% of the patients. Oral AEs were seenin 43% of patients after JC SLIT and 55% after HDM SLIT (p=0.49). Only one patient was unable to continue SLIT because of marked throat irri-tation with HDM, and in all the other patients the symptoms improved. No case of anaphylaxis was seen but three children had severe oral irrita-tion for which one needed a reduction of the JC SLIT maintenance dose and the other two needed an interruption of HDM SLIT which was finallyreconducted with the addition of daily anti-histaminic drugs. Interestingly, Dual SLIT was not a significant risk factor for AEs and the treatmentwas tolerated as well as single allergens SLIT. In conclusion, SLIT seems to be a safe treatment, well-tolerated even in children with multiple al-lergies.

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PosterSession

PE31-20 Powder hydroxypropylmethylcellulose as add-on to nasal steroid improves the outcomes of nasal polyps conservative treatment

Todor A Popov1), Tania Z Kralimarkova2), Diana Hristova2), Tihomir B Mustakov2), George Christoff2) (Department of Occupational Disease, Univer-sity Hospital St. Ivan Rilski, Bulgaria1); Medical University Sofia, Bulgaria2))

Background: Patients with chronic rhinosinuitis with nasal polyps (CRSwNP) are usually subjected to aggressive pharmacological and/or surgi-cal treatment. Temporary relief and remission, though, is most often followed by re-surge of the nasal polyps. We present the beneficial results weachieved by adding a mucoadhesive sealant, powder hydroxylpropylmethylcellulose (pHPMC), to maintenance intranasal steroid (INS) after pulsetreatment with oral corticosteroid.Methods:We followed-up 10 patients with CRSwNP (median age 52, range 37-61 years; 7 women; 6 asthmatics),who were treated by repeated boosts of oral steroid treatment on re-surge of their polyps followed by maintenance INS treatment. We comparedthe duration of their temporal remission (in weeks) after a preceding oral steroid boost (30 mg of prednisolone for 10 days) and subsequent INS(mometasone furoate, 2x50mcg per nostril per day) and, following a re-surge of their polyps, another identical treatment regimen was prescribed,when after the prednisone boost a puff of pHPMC was added after each application of INS. The duration of the remission was defined as the timelapse between appearance of the sense of smell after the oral steroid boost and its disappearance as a sign of re-surge of the polyps. Results: Themean duration±s.e.m. of the relative remission after INS maintenance alone was 9.3±1.2 weeks vs. 25.2±4.2 weeks when maintenance treatmentinvolved pHPMC (P=0.003). Four patients on INS + pHPMC never lost their sense of smell, the duration of their remission was accepted to end atthe time of the analysis of the data. Interestingly, patients on INS + pHPMS reported fewer adverse events. Conclusion: pHPMC may present auseful add-on approach to maintenance therapy of subjects with CRSwNP, by sealing INS to the intranasal structures and by acting as a barrieragainst noxious ambient influences.

257

PosterSession

Poster Session 32Treatment for adult asthma 1

PE32-1 Evaluation of the qualitative assessment of asthma management by the Health Insurance Review and Assessment Service(HIRA)

Hyeon-Jong Yang1), Nam-Eun Kim2), Sanghun Lee3), Sungho Won1,4,5) (Department of Pediatrics, Soonchunhyang University Seoul Hospital, Repub-lic of Korea1); Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Republic of Korea2); Departmentof Medical Consilience, Graduate School, Dankook University, Republic of Korea3); Interdisciplinary Program of Bioinformatics, Seoul National Uni-versity, Republic of Korea4); Institute of Health and Environment, Seoul National University, Republic of Korea5))

Background: The Health Insurance Review and Assessment Service (HIRA) in South Korea has applied the qualitative assessment of asthmamanagement based on the guidelines since 2013, and classified primary clinics into two categories as“satisfactory clinics”and“unsatisfactoryclinics”, but studies are lacking on whether these assessments are properly performed and contribute toward reducing asthma exacerbations.Methods:We investigated whether HIRA’s quality assessments decrease asthma exacerbations using national health insurance claims data from2013-2017, including 83,375 primary-clinic and 15,931 tertiary-hospital patients with asthma classified into four groups based on disease severityaccording to the monthly prescribed amount of asthma medication using the statistical K-means clustering method. The associations of HIRA as-sessment with asthma exacerbation were analyzed by generalized estimating equation (GEE) modeling. Results: As a result of the clusteringanalysis, the patients with asthma were classified into four clusters (cluster I=83,195, II=11,116, III=16,692, and IV=2,965). The asthmaexacerbation-rate was increased by the level of asthma cluster (I; 16.5%, II=28.1%, III=37.4%, and IV=51.9%, p<.01). The GEE models showed thatthe risk of exacerbation was lower in the satisfactory clinics than unsatisfactory clinics. Conclusion: Asthma exacerbations could decrease byguideline-based management at the national level, and our results suggested that appropriate public quality assessment could be helpful in reduc-ing asthma exacerbations.

PE32-2 Real-world study of prescription pattern of inhaled corticosteroids in adult asthma

Yu Nakanishi1), Hiroshi Iwamoto1), Satoshi Nakao1), Naoko Higaki1), Kakuhiro Yamaguchi1), Shinjiro Sakamoto1), Yasushi Horimasu1),Takeshi Masuda1), Naoko Matsumoto2), Taku Nakashima1), Shintaro Miyamoto1), Yojiro Onari3), Kazunori Fujitaka1), Yoshinori Haruta4),Hironobu Hamada1), Soichiro Hozawa5), Noboru Hattori1) (Department of Respiratory Internal Medicine, Hiroshima University Hospital, Japan1);Department of Respiratory Internal Medicine, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Japan2); Department of Respira-tory Internal Medicine, Hiroshima Mazda Hospital, Japan3); Haruta Respiratory Clinic, Japan4); Hiroshima Allergy & Respiratory Clinic, Japan5))

Background: Inhaled corticosteroids are the mainstay of treatment for chronic asthma. Various inhaler devices exist for the treatment of asthma,and device characteristics and formulation is important to determine clinical response. There has been accumulating evidence that switching in-haler device could improve asthma control when the patients had suboptimal asthma control with one inhaler device. Therefore, switch of inhalerdevices may be attempted in patients with difficult to treat asthma, but real-world prescription pattern has not been clarified. Objectives: The ob-jectives of this study were to investigate real-world prescription pattern of inhaled corticosteroids in adult asthma and to investigate the relation-ship between the prescription history and asthma control, severity, and exacerbations. Results: A total of 341 adult asthma patients who had beentreated with inhaled corticosteroids from 2018 to 2019 and with disease duration of two or more years were included in this analysis. The meanduration of asthma was 11.0 years, and 35.5% of the patients had ever used only one type of device, 38.1% had ever used 2 types of devices, andthe rest of the patients had ever used more than 2 types of devices. Self-reported treatment adherence and patients satisfaction to inhaler was notassociated with how many types of inhaler devices had been ever prescribed. The patients with a history of greater number of inhaler deviceswere significantly associated with the following characteristics: (1) higher treatment steps (2) poorer asthma control (3) more frequent exacerba-tions in the previous 2 years (4) lower FEV1 (5) use of oral corticosteroids (6) use of asthma biologics. Conclusion: This real-world study showedthat various kinds of inhaler devices had been attempted in patients with poor asthma control and more frequent exacerbations and in thosetreated with oral corticosteroids and biologics.

PE32-3 The association of hyposmia on cognitive function and asthma control in asthmatics

Hyo-In Rhyou, Young-Hee Nam (Department of Internal Medicine, College of Medicine, Dong-A University, Republic of Korea)

Background: Chronic rhinosinusitis (CRS) and/or allergic rhinitis (AR) are common comorbidities in asthmatics, and they are known to influencethe symptoms and prognosis of asthma. Hyposmia frequently occurs in CRS and/or allergic AR, and has been reported to affect cognitive func-tion in previous studies. However, hyposmia in asthma patients has been relatively overlooked by physicians. We conducted a cross-sectionalstudy on association of hyposmia on cognitive function and asthma. Methods: This cross-sectional study included a total of 145 asthma patientswho visited in Dong-A University Hospital from July 2019 to February 2020. We evaluated olfactory and cognitive function by YSK OlfactoryFunction (YOF) test and Korean Version of Montreal Cognitive Assessment (K-MoCA), respectively. We compared the demographic and clinicalcharacteristics and cognitive function between asthma patients with hyposmia (n=94) and asthma patients with normosmia (n=51) according toYOF score. Results: There were no significant differences in sex, smoking status, economic status, education, comorbidities as well as CRS and/orAR, lung function, and inhaled corticosteroid treatment between the two groups. Patients in hyposmia group were significantly older (61.76±13.46 years vs. 54.43±14.92 years, P=0.003) and had longer duration of asthma (111.27±87.80 months vs. 82.57±56.93 months, P=0.019) than pa-tients in normosmia group. The proportion of patients with history of life-threatening asthma exacerbation was observed much more in the hy-posmia group than in the normosmia group (7.5% vs. 0.0%, P=0.045). When the effect of age was excluded through partial correlation analysis,YOF score was positively correlated with K-MOCA score (r=0.205, P=0.004). Conclusion: Hyposmia is associated with cognitive dysfunction inasthmatics, and patients with hyposmia more likely have experienced life-threatening asthma exacerbation. Further study of the association ofhyposmia on cognitive dysfunction and asthma control is needed in the future.

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PosterSession

PE32-4 Prevalence, underlying diseases and patient characteristics of chronic cough patients in Japan: a web-based survey

Kotoba Okuyama, Keisuke Tobe, Takekazu Kubo, Masashi Kikuchi, Yirong Chen, Jonathan Schelfhout, Shigeru Tokita, Machiko Abe (Medical Af-fairs, MSD K.K., Japan)

Background: Chronic cough (CC) is defined as persistent cough with a duration of at least 8 weeks. CC population has not been well studied. Thisstudy aimed to assess the prevalence, the underlying diseases and patient characteristics of CC patients in Japan.Method: Respondents above 20-years-old who completed the 2019 Japan National Health and Wellness Survey (NHWS) were invited to participate in the online quantitative CCsurvey if they did not have lung cancer or interstitial lung disease and not currently taking ACE inhibitor to treat high blood pressure. Both theNHWS and the cough questionnaire were designed to recruit respondents that were nationally representative. The severity of cough was meas-ured by a visual analogue scale (VAS) from 0 (no cough) to 100 (extremely severe cough). CC patients were classified as refractory chronic cough(RCC) if the medication used related to their underlying conditions did not resolve CC adequately. Descriptive analyses were performed to esti-mate the prevalence and to describe the CC patients. Results: Among the 24,015 NHWS respondents, 694 (2.89%) reported concurrent CC and1,030 (4.29%) reported CC in the last 12 months at the time of the survey. In the online quantitative CC survey, 568 patients having CC at the timeof the survey were included. The average of the age of the CC population was 56.0 years old (SD=15.2) and 61.1% were male. Prevalence of CCwas the highest among male aged 60 or above (2.83%). Among all CC patients, 29.4% were current smokers. Cough severity was 41 on averageamong the CC patients. The most common underlying conditions were allergic rhinitis (10.3%), asthma (9.6%) and cough variant asthma (8.5%),with 35.6% not informed as to an underlying condition. Approximately half (48.8%) of the CC patients took medication. Among all CC patients,16.0% were classified as RCC. Conclusion: This study generated novel real-world information on CC patients in Japan, which provides valuable in-sights for future treatment development for this group of patients.

PE32-5 Development of a new mouthpiece for pMDI

Reiko Ito1), Kazuto Nakagawa2), Fujio Koeda3), Yasuhiro Gon1) (Department of Respiratory Medicine, Department of Internal Medicine, Nihon Uni-versity School of Medicine, Japan1); Department of Conceptual Design, Nihon University College of Industrial Technology, Japan2); Department ofDesign, Nihon University College of Art, Japan3))

Background: The correct use of inhaler devices is essential to obtain the enough therapeutic effects in the inhalation treatments of Asthma andCOPD. It is reported that the descending position of a tongue in mouth is quite important in order to transfer the adequate amount of drug to theairway. Therefore, we aimed to develop the new types of mouthpiece for inhalation of pMDI whether the tongue is in the right position. Aims: Tocheck the position of a tongue is descending and stays in the preferable by using the new mouthpieces for pMDI. Methods: We developed the 2types of mouthpieces for pMDI which has 70 degrees angle in inlet (Mouthpiece No.1), and 80 degrees angle (Mouthpiece No.2), and asking healthyvolunteers to use both types of mouthpiece. Subjects were the 19 volunteers (age, 22-77; 12 men & 7 women). We photographed by the intraoralthe positions of their tongues, with the new mouthpieces and without, then we measured and evaluated the distance between the tongue and thesoft palate in the posterior pharyngeal wall area, using the software“Image J.”Results: In the case of using mouthpiece No.1, the area of the pos-terior pharyngeal wall has widened up to 414%. By using Mouthpiece No.2, the area increased further wider to 610% (p<0.0001). In addition, it wasobserved that the distance from the soft palate to the tongue also stretched 234% by No.1, and 329 by No.2. There was no significant differenceamong 2 types of mouthpieces. Conclusions: The usage of those new mouthpieces for pMDI with angles in the inlet, works prominently to keepthe tongue lower and to widen the posterior pharyngeal wall area. As the position of the tongue descending by the inhaler, the area of pharyngealrear wall will get wider and be good use for the inhalation treatments.

PE32-7 Triple therapy with budesonide/glycopyrrolate/formoterol is effective for asthma-COPD overlap

Yoshihisa Ishiura1), Masaki Fujimura2), Noriyuki Ohkura3), Johsuke Hara3), Kazuo Kasahara3), Yusuke Sawai1), Takeshi Tamaki1), Toshiki Shimizu1),Shosaku Nomura1) (First Department of Internal Medicine, Kansai Medical University, Japan1); Respiratory Medicine, National Hospital Organiza-tion Nanao Hospital, Japan2); Respiratory Medicine, Kanazawa University Hospital, Japan3))

Asthma-chronic obstructive pulmonary disease overlap (ACO), characterized by airway limitation, is an important condition with high incidenceand mortality. Although some guidelines recommend triple therapy with inhaled corticosteroids/long acting muscarinic antagonists/long-actingβ2 agonists, this treatment approach is based on the extrapolation of data from studies of asthma or chronic obstructive pulmonary disease(COPD) alone. A 12-week, randomized, open-label cross-over pilot study was conducted in 19 patients with ACO to investigate the effect of tripletherapy with glycopyrrolate (GLY) 50 µg/day on budesonide/formoterol fumarate (BUD/FORM) 640/18 µg/day. The study period included a 4-week wash-out, 4-week run-in, and 4-week treatment period. Respiratory function tests, fractional exhaled nitric oxide (FeNO), a COPD assess-ment test (CAT) and an asthma control questionnaire (ACQ) were carried out 0, 4, and 8 weeks after randomization. A total of 19 patients withstable ACO (19 males and no females) with a mean age of 70.7±7.6 years (±standard deviation, SD; range 5583 years) participated in this study.All patients were ex-smokers with a smoking history of 63.1±41.1 pack-years (±SD). Mean values for inspiratory capacity (IC), an index of hyper-inflation of the lung that causes exertional dyspnea and reduced exercise, were 1.93 L (±0.47 L) after the run-in, 1.85 L (±0.51 L) after the BUD/FORM dual therapy period and 2.11 L (±0.58 L) after the BUD/GLY/FORM triple therapy period. IC values after the BUD/GLY/FORM tripletherapy were significantly higher than those after the run-in (p≦0.02). FeNO values, ACQ, and CAT scores were not significantly different amongthe run-in, wash-out, and triple-therapy periods. The present pilot study showed that triple therapy with BUD/GLY/FORM results in an improve-ment in lung function parameters including IC, indicating the potential value of triple therapy as standard treatment for ACO.

259

PosterSession

PE32-8 Effect of Japanese cedar pollen sublingual immunotherapy for asthma patients with Japanese cedar pollinosis

Sumiko Abe1), Jun Ito1), Yuuki Sandhu1), Takayasu Watanabe1), Takayasu Nishimaki1), Yukari Oyama1), Shoko Ueda1), Hitoshi Sasano1),Yuki Tanabe1), Tomohito Takeshige1), Sonoko Harada2), Ryo Atsuta1), Norihiro Harada1), Kazuhisa Takahashi1) (Department of Respiratory, Jun-tendo Hospital, Japan1); Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Japan2))

Background: Considering the concept of“one airway one disease”, which considers the entire respiratory tract as one target organ, asthma thatworsens during the seasons of Japanese cedar pollinosis (JCP) may improve by treatment of JCP. Since 2014, sublingual immunotherapy (SLIT)for JCP is available in Japan, but there are few reports of the SLIT for asthma patients with JCP. Therefore, we investigated whether SLIT forJCP improves asthma control in asthmatic patients with JCP. Methods: 24 patients aged 23-72 with asthma and JCP were treated with SLIT forJCP in our hospital from Jun 2016 through Oct 2019. 14 patients were eligible for the efficacy analyses. Asthma Control Test score, SACRA ques-tionnaire, pulmonary function tests, forced oscillation technique (FOT), the fractional exhaled nitric oxide levels, etc. were evaluated at baselineand one year after treatment. Result: Their subjective symptoms score of rhinitis and asthma in the SACRA questionnaire were significantly im-proved. Moreover, FOT detected significant changes in lung function. Conclusion: These findings suggested that the effect of SLIT for JCP inasthmatic patients with JCP may improve not only pollinosis but also asthmatic symptoms.

PE32-9 Prediction of future risks of asthma exacerbation using fractional exhaled nitric oxide and asthma control test questionnaire

Manabu Uematsu, Junpei Saito, Suguru Sato, Atsuro Fukuhara, Yasuhito Suzuki, Mami Rikimaru, Takaya Kawamata, Ryuichi Togawa,Yuki Sato, Takefumi Nikaido, Yoshinori Tanino, Yoko Shibata (Depatrtment of Pulmonary Medicine, Fukushima Medical University School ofMedicine, Japan)

Rationale:We have reported that history of asthma exacerbation (AE) in the past year, fraction of exhaled nitric oxide (FeNO) and Asthma Con-trol Test (ACT) were independent predictors of AE in the next year. However it is unclear whether combination use of these markers can bemore useful to detect AE. Objectives: To investigate whether concomitant use of FeNO and ACT could be more predictive of AE than single useof each marker prospectively.Methods: At the study entry, FeNO and ACT were performed in 159 asthmatics. All asthmatics were divided intofour groups (ACThigh/FeNOhigh, ACThigh/FeNOlow, ACTlow/FeNOlow, and ACTlow/FeNOhigh) using cut-off values of FeNO and ACT (54.2ppb and 24.5 points) obtained from our previous study. Then, we prospectively followed them over a year to compare exacerbation rates amongfour groups. Results: In total, 99 of 159 asthmatics continued to visit our outpatient clinic over the course of the study. Of these, 22 asthmatics hadat least one AE over a year. In asthmatics with a history of AE in the past year, exacerbation rates were higher in the 3 groups (ACThigh/FeNO-high, ACTlow/FeNOlow, and ACTlow/FeNOhigh) compared to the group of ACThigh/FeNOlow. On the other hand, in asthmatics with no his-tory of AE in the past year, exacerbation rates were significantly higher in the group of ACTlow/FeNOhigh than in other three groups. Conclu-sions: Concomitant use of FeNO and ACT may provide more useful information on predicting a future risk of AE, especially in asthmatics with-out a history of AE in the past year.

PE32-10 Oral corticosteroid could be a risk factor for diabetes in patients with asthma

Yasuhiro Tomita1,2), Yuma Fukutomi2), Mari Irie3), Kazuhiro Azekawa4), Yoichi Nakamura5), Chiharu Okada6), Terufumi Shimoda7), Miku Kuriki1),Katsuyuki Kojima1), Masami Taniguchi2) (Respiratory Medicine, Tokai Central Hospital, Japan1); Clinical Research Center for Allergy and Rheuma-tology, National Hospital Organization Sagamihara National Hospital, Japan2); Nihon Medical Insurance Institute Ltd., Japan3); MHI Co., Ltd., Ja-pan4); Medical Center for Allergic and Immune Diseases, Yokohama City Minato Red Cross Hospital, Japan5); Headquarters, National Hospital Or-ganization, Japan6); Clinical Research Center, National Hospital Organization Fukuoka Hospital, Japan7))

Background: Oral corticosteroid use could cause several adverse effects. These days, although various antibody medicines had been launchedand the use of oral corticosteroids is decreasing, there are still many patients using oral corticosteroids as a controller for asthma. It is importantto understand the risk of oral corticosteroid in asthma patients.Methods: A retrospective cohort study was conducted using the data from healthinsurance claims from 3 health insurance societies April 2011-thru-March 2015. Among the patients with asthma over 20-year-old, chi-square testwas performed to investigate the relationship between corticosteroid prescription days and the prevalence of diabetes in the fiscal year 2014. (n=2,859) Results: Significant relationship was detected between oral corticosteroid prescription days and the prevalence of diabetes. (none; 2.1%, 1-365 days/4year; 2.3%, 366 days/4year-; 12.1%, p=0.001) Conclusions: Long term oral corticosteroid use for the treatment of asthma could be re-lated to the prevalence of diabetes.

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PosterSession

PE32-11 Efficacy and safety of once-daily, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI inJapanese patients with inadequately controlled asthma: the CAPTAIN study

Yoichi Nakamura1), Soichiro Hozawa2), Hironori Sagara3), Hiroyuki Ohbayashi4), Andrew Fowler5), Laurie Lee6), Jodie Crawford5), Jun Tamaoki7)(Medical Center for Allergic and Immune Diseases Yokohama City Minato Red Cross Hospital, Japan1); Hiroshima Allergy and Respiratory Clinic,Japan2); Showa University School of Medicine, Japan3); Tohno Chuo Clinic, Japan4); GlaxoSmithKline, UK5); GlaxoSmithKline, USA6); GlaxoS-mithKline, Japan7))

Background: For patients with uncontrolled asthma, despite inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy, treatment options include increas-ing ICS dose or adding long-acting muscarinic antagonist. To evaluate consistency of outcomes in an ethnically diverse population, we report the efficacy and safety offluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in a Japanese cohort from the CAPTAIN study. Method: CAPTAIN: Phase IIIA, random-ized, double-blind, active-controlled, parallel-group study in adults with asthma, pre-bronchodilator FEV1≧30% and <85% predicted, Asthma Control Questionnaire(ACQ-6) score ≧1.5. Excluded: current/former smokers (≧10 pack-years). Treatment following ICS/LABA run-in: once-daily FF/VI (100/25, 200/25mcg) or FF/UMEC/VI (100/31.25/25, 100/62.5/25, 200/31.25/25, 200/62.5/25mcg) (Ellipta inhaler). Endpoints: trough FEV1 (primary), 3h post-dose FEV1, ACQ-7, and EvaluatingRespiratory Symptoms (E-RS) Asthma questionnaire total score at Week 24; moderate/severe exacerbations (key secondary, Weeks 152). For non-lung function end-points, FF doses were pooled for each UMEC dose. Safety was also assessed. Results: In the intention-to-treat Japanese subpopulation (n=229; 63 centers), all FF/UMEC/VI groups experienced greater improvements from baseline in trough FEV1 versus FF/VI. The largest improvements were seen with UMEC-62.5 (FF-100/UMEC-62.5/VI: 105mL [95% confidence interval: -5, 216]; FF-200/UMEC-62.5/VI: 69mL [-42, 179]; FF-100/UMEC-31.25/VI: 53mL [-60, 165]; FF-200/UMEC-31.25/VI: 29mL [-82, 140]). Similar effects were seen on 3h post-dose FEV1. Consistent with the overall study population, FF/UMEC-62.5/VI groups showed improvements frombaseline versus FF/VI for most efficacy endpoints (ACQ-7: -0.08 [-0.29, 0.13]; E-RS Asthma: -0.78 [-1.92, 0.36]), which were of greater magnitude than for FF/UMEC-31.25/VI (0.09 [-0.12, 0.30] and 0.39 [-0.75, 1.54], respectively). Moderate/severe exacerbations were infrequent (n=47 [21%]), limiting power to detect differences be-tween treatment groups. The safety profile of FF/UMEC/VI was generally consistent with that seen in the overall population. Conclusion: Among the CAPTAINJapanese cohort, FF/UMEC/VI was associated with numerical improvements in trough FEV1 versus FF/VI, with the greatest improvements across most efficacyendpoints for UMEC-62.5mcg treatment groups. This analysis suggests that FF/UMEC/VI is an effective and well-tolerated treatment option for Japanese patientswith inadequately controlled asthma, consistent with findings of the multi-regional CAPTAIN program. Funding: GlaxoSmithKline (205715/NCT02924688).

PE32-12 Adrenal insufficiency (AI) as an underestimated risk factor in severe asthma

Michiko Haida1), Katsutoshi Ogawa2), Akihiko Hashiguchi3), Takahiro Inoue1) (Hanzoumon Hospital, Japan1); Amica Lifesience, Japan2); BiomedicalLaboratory, Japan3))

Rationale: Adrenal insufficiency (AI) in asthma is often under-estimated due to their indefinite symptoms. We measured adrenal function inasthma patients in order to characterize the clinical profile of severe AI. Methods:We examined 128 successive asthma cases for possible AI by(1) Diurnal cortisol at 6am, 11am, 15pm, 23pm, (2) ACTH provocation test (3) 24 urinary CS for 2days. Diurnal cortisol level less than 5µg/dl at allsampling points, peak CS under 25µg/dl in ACTH-provocation test was defined as severe AI. Urine level was used only as reference due to unsta-ble sampling in elderly cases. Results: Severe AI was found in 21 cases (16.4%) all of which had past history of high dose OCS treatment except inone, who developed AI after unknown viral infection (KH, M, 62yo) while traveling abroad. Steroid dependent asthma was found in 9 (42.9%),treated together with biologics. In 3 cases (14.3%), use of systemic CS for other purpose, ie, lymphoma (FM, F, 48yo), lumber pain (NS, M, 69yo; ER,F, 36yo), seemed to trigger both AI and asthma. Others with AI had EGPA (KM, M, 35yo), chemical hypersensitivity syndrome (IM, F, 46yo). Theyhad indefinite symptoms, ie, cough, fatigability, which recovered after replacement therapy with hydrocortisone. Compared to remaining 107cases, those with severe AI had past history of high dose steroid (p≦0.0000), early onset of asthma (p≦0.0377), higher frequency of acute exacer-bation (P≦0.0055), history of sinusitis (p≦0.0009), frequent hospital admission (p≦0.0368), biologic use (p≦0.0136) and passive smoking (p≦000).They also had tendency to repeat remission (p≦0.055) and recurrence (p≦0.083), chemical hypersensitivity (p≦0.08), nervousness measured byCMI (p≦0.096), but less depression measured by CES-D (p≦0.069), and their stature tended to be higher (p≦0.081). Discussion: Some of the fea-tures often found in severe asthma may be signs that reflect adrenal insufficiency and if suspected should be diagnosed more accurately by meas-uring the actual cortisol in appropriate conditon so that they can be treated if necessary. Conclusion: Those with severe asthma may acquire bet-ter control if they are assessed properly and treated for their underlying AI.

PE32-13 Comparison of combinations of ICS, LABA, and LAMA as triple agent in patients with BA, COPD, and ACO patients

Taichi Mochizuki, Yasushi Inoue, Ryuta Ueda, Hiroyuki Arai, Yasuo To, Seisuke Nagase, Akira Umeda, Kenji Tsushima (Department of Respira-tory Medicine, School of Medicine, International Medical Welfare University, Japan)

Background: In Japan, a current hot topic in chronic obstructive pulmonary disease (COPD) is the use of two“fixed triple”combinations of in-haled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) in a single inhaler in patients withCOPD. However, there is a lack of reports directly comparing their effectiveness. Objective: To compare the effectiveness of the two available in-haled“fixed triple”ICS/LABA/LAMA combinations (budesonide/formoterol/glycopyrrolate and fluticasone/vilanterol/umeclidinium) in pa-tients with bronchial asthma (BA), COPD, and BA and COPD overlap (ACO). Methods: We conducted a retrospective review of the electronicmedical charts of 59 patients with stable-phase BA, COPD, and ACO receiving treatment with any ICS, LABA, and LAMA open triple agents for30 months (from July 1, 2017 to December 31, 2019). We compared changes after 12 weeks of treatment on the following clinical outcomes: variousrespiratory functions [Forced vital capacity (FVC)], [One-second forced expiratory volume (FEV1.0)], [Inspiratory capacity (IC)], modified MedicalResearch Council dyspnea score (mMRC), Asthma Control Test, and number of exacerbations of BA, COPD, and ACO. Results: After the changeto the“fixed triple”ICS/LABA/LAMA combinations, the rate of exacerbation was higher in the BA patients (P>0.05). The“fixed triple”ICS/LABA/LAMA combinations, the Vireztori and the Terrilzy groups, showed improvement in the mMRC score in COPD and ACO patients (P<0.05). There was no statistically significant difference in the other tests (P>0.05). Conclusions:With regard to the transition to the use of“fixed tri-ple”ICS/LABA/LAMA combinations, there is a need to accumulate cases and to make a selection taking into consideration the patient back-ground and device preference.

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PosterSession

Poster Session 33Treatment for adult asthma 2

PE33-1 Stratification by blood eosinophil counts and levels of fractional exhaled nitric oxide characterizes subclasses of patients withsevere asthma

Hidetoshi Iemura, Tomoyuki Soma, Erika Naito, Yuki Hoshino, Sachiko Miyauchi, Kazuki Katayama, Ryu Sekiya, Yoshitaka Uchida,Kazuyuki Nakagome, Makoto Nagata (Department of Respiratory Medicine, Saitama Medical University, Japan; Allergy Center, Saitama MedicalUniversity, Japan)

Background: Blood eosinophil counts and levels of fractional exhaled nitric oxide (FeNO) are recognized as markers of type 2 inflammation inasthma. Increases of them may determine clinical features of asthma.Methods: Patients with severe asthma (SAs) defined by criteria of JapaneseSociety of Allergology guideline were enrolled. We obtained their clinical date from medical records. Additionally, induced sputum, FeNO and pul-monary function were evaluated. Of eosinophil count and FeNO, thresholds values to distinguish SAs with eosinophil ratios in sputum 2% from allof SAs were determined by using receiver operating characteristic curve (ROC) analysis. Eligible SAs were classified into four subgroups basedon estimated thresholds value. Clinical features were analyzed among subgroups of SAs. Results: One hundred two SAs were enrolled. Adequatesputum samples were successfully obtained from 36 SAs. B-EOS 300/L (82.0%, p=0.001) and FeNO38 ppb (82.7%, p=0.005) were decided to use asoptimal thresholds values to distinguish sputum eosinophilia. Patients were divided into four subgroups: high or low blood eosinophils and high orlow levels of FeNO. SAs with both high b-EOS (300/L) and high FeNO (38 ppb) (23%) showed the highest frequency of severe acute exacerbations(SAEs) (p=0.009), lower %FVC (p=0.04) and higher prevalence of chronic sinusitis (CSs) (p=0.016). SAs with high b-EOS with low FeNO (26%)showed higher frequency of SAEs, lower %FVC and higher prevalence of CSs. SAs with low b-EOS with high FeNO (1%) showed the highestprevalence of CSs. SAs with low b-EOS and low FeNO (47%) showed the lowest frequency of SAEs, higher %FVC and lower prevalence of CSs.Ratio of SAs with sensitization to environmental allergens were not different among 4 SAs subgroups. Conclusion: SAs with high type 2 inflam-mation biomarkers in airway and blood remain not-well controlled condition despite of guideline treatment and have upper airway comorbidity.

PE33-2 The analysis of Tfh/Tfr cells and house dust mite (HDM)-specific immunoglobulins in patients with atopic asthma comorbid withallergic rhinitis receiving HDM-sublingual immunotherapy

Katsunori Shigehara, Ryuta Kamekura, Shingo Ichimiya (Department of Human Immunolgy, Research Institute for Frontier Medicine, SapporoMedical University, Japan)

Background: To investigate the role of T follicular helper (Tfh)/T follicular regulatory (Tfr) cells for house dust mite (HDM; Der pteronyssinusand Der farinae)-specific immunoglobulins, we performed comprehensive analysis including T/B regulatory (Treg/Breg) cells in HDM-sublingualimmunotherapy (SLIT) receiving patients with atopic asthma (AA) comorbid with allergic rhinitis (AR). Methods: Sixteen patients with AAcomorbid with AR were participated. All patients took a HDM-tablet (10000 JAU) daily. We measured these cells from PBMC using FACS(FACSCanto) and plasma HDM-sIgs (IgE and IgG4) by ELISA at beginning of administration, after 3months, 6 months, and 12 months. Results:Percentage of Tfh2 cells gradually decreased and percentage of Tfh1 cells conversely increased during 12 months. HDM-specific IgE decreasedand IgG4 increased after 3 months. Percentage of Tfr cells showed no significant change during 12 months, however, these cells indicated nega-tive correlation with those of Tfh2 cells and positive correlation with those of Tfh1 cells at 3 months. Percentage of Treg cells gradually increasedduring 12 months and also showed negative correlation that of Tfh2 cells at 3, 6, and 12 months. Furthermore, HDM-sIgE was good positive corre-lated with percentage of Breg cells before administration, at 3 months and 6 months, however, both changes from beginning of administration to 6months showed negative correlation. Conclusion: These findings demonstrated that Tfh2 cells were inhibited by Tfr and Treg cells, therefore,gradually Tfh2 cells decreased with HDM-specific IgE. Breg cells strictly prevent HDM-specific IgE production.

PE33-3 Transcriptome analysis of patients with refractory asthma for predicting the efficacy of bronchial thermoplasty

Satoshi Ano1), Norihiro Kikuchi1), Masashi Matsuyama2), Masayuki Nakajima2), Yuzuru Kondo3), Michiko Masuda1), Shizuka Arai1), Hajime Osawa2),Yukio Ishii1,2), Nobuyuki Hizawa2) (Department of Respiratory Medicine, National Hospital Organization Kasumigaura Medical Center, Japan1); De-partment of Respiratory Medicine, University of Tsukuba, Japan2); Department of Diagnostic Pathology, National Hospital Organization Kasumi-gaura Medical Center, Japan3))

Background: Bronchial thermoplasty (BT) is an endoscopic therapy employed for the treatment of refractory asthma. However, no predictivefactors are available that determine the effectiveness of BT in treating asthma patients. Objective: The present study aimed to comprehensivelyanalyze the RNA samples from airway bronchial tissues of severe asthma patients treated by BT, and to characterize each patient as a BT re-sponder or non-responder. Methods: Eight severe asthma patients scheduled to undergo BT and bronchus biopsies were recruited in this studybefore the procedures were conducted. Extracted RNA samples from the bronchial tissues were sequenced, followed by differential gene expres-sion analysis. Results: Subjects with Asthma Quality of Life Questionnaire (AQLQ) score change of 0.5 or greater, for a period of 12 months wereconsidered as BT responders. Non-responders exhibited a score change of <0.5 for a period of 12 months. The histopathology findings were simi-lar to those reported in past. However, no significant differences in the expressions of α-smooth muscle actin (α-SMA) and protein gene product(PGP) 9.5 were observed between responders and non-responders. Transcriptome analysis revealed 67 differentially expressed genes between re-sponders and non-responders. Seven specific genes overlapped with previous reports. Of these, five genes, UPK1B , SLC39A8 , TCN1 , P4HB andPIP , matched with the genes differentially expressed in severe asthma patients from Meta-analysis, and two of them, CHP2 and CA2 , matchedwith genes whose expression changed over BT sessions. Conclusion: Our results show the possible characteristics for determination of respond-ers at a transcriptomic level. These findings may help to distinguish BT responders from non-responders.

262

PosterSession

PE33-4 Investigation of the relationship between serum TSLP levels and other cytokines and patient background in adults with asthma

Mayumi Yamamoto, Tomoko Kawahara, Hatsuko Mikuni, Haruna Sato, Tomoki Uno, Yoshitaka Uchida, Yousuke Fukuda, Tomoyuki Kimura,Megumi Jinno, Kuniaki Hirai, Yoshito Miyata, Shin Ohta, Hideki Inoue, Tetsuya Homma, Yoshio Watanabe, Shintaro Suzuki, Akihiko Tanaka,Hironori Sagara (Division of Respiratory Medicine and Allergology, Showa University Hospital, Japan)

Background: Recently, the benefits of anti-TSLP antibodies in patients with severe asthma have been reported, but how TSLP should be inter-preted in the blood of asthmatic patients is not fully understood.Methods: A total of 201 patients diagnosed with asthma were participated in thisstudy. Patient backgrounds, such as BMI, age of onset, duration of disease, number of acute exacerbations per year, treatment, severity, complica-tions, FEV1.0, FENO, IgE and eosinophil count, was investigated retrospectively. IL5, IL13, IL33, TSLP and G-CSF in patient’s serum were meas-ured using a commercially available ELISA kit (R&D systems). The relationship between these cytokines and patient background was studied.Results: There was no significant correlation with BMI, duration of disease, number of acute exacerbations per year, treatment, severity, compli-cations, FEV1.0, FENO, IgE and eosinophil count with serum TSLP. TSLP and age of asthma diagnosis had a weak negative correlation (r=-0.2, p=0.0003). On the other hand, among the cytokines in the serum of asthma patients, TSLP and IL13 were significantly correlated (r=0.67, p<0.0001).Similarly, eosinophil count, FENO and IgE of the patients were weakly correlated (FENO vs eosinophil count; r=0.32, p<0.0001, FENO vs IgE; r=0.30, p<0.0001, eosinophil count vs IgE; r=0.20, p=0.0043). Conclusion: The presence of TSLP in the blood suggests the presence of type 2 inflam-mation in patients with asthma who have been positive, but the clinical implications of this and its application require further investigation.

PE33-5 Changes of the clinical and serum biomarkers after anti-IL5 treatment in patients with severe eosinophilic asthma

JaeHyuk Jang, Young-Soo Lee, Seong-Dae Woo, Eun-Mi Yang, Yoo Seob Shin, Young-Min Ye, Hae-Sim Park (Department of Allergy & Clinical Im-munology, Ajou University School of Medicine, Republic of Korea)

Background: Patients with severe asthma have been suffering from frequent asthma exacerbations, where eosinophil is a major effector cell inairway inflammation, and anti-IL5 treatment is an effective treatment modality. Methods: Thirteen patients with severe eosinophilic asthma(SEA) who had been treated with anti-IL5 treatment (reslizumab, 100mg monthly SC) for 6 months, were enrolled at Ajou University Hospital (Su-won, South Korea). Clinical parameters such as total blood eosinophil count (TEC), FEV1% and fractional exhaled nitric oxide (FeNO) levels werecompared before/after anti-IL5 treatment. Changes in serum levels of eosinophil-derived neurotoxin (EDN), periostin (PON), TGF-β1 were ana-lyzed by ELISA. Results: Serum EDN levels as well as TEC decreased significantly after 1 month of the treatment; FEV1% increased after 2months of treatment (P<0.05, respectively), while no changes were noted in FeNO levels. A positive correlation was observed between TEC andserum EDN levels (r=0.49, P=0.1). Significant negative correlations were noted between age and TEC/EDN levels (r=-0.62, P=0.02; r=-0.59, P=0.03). When the EDN-responder group was defined if serum EDN level decreased (≧30%) after the first month of treatment, TEC was signifi-cantly higher in the responder group than in the non-responder group (1,017±495.6/L vs. 500.7±252.0/L, P=0.039). Reduction of serum EDN lev-els was significantly correlated with baseline TEC and FeNO levels (r=0.58, P=0.04; r=0.65, P=0.02). When the FeNO-responder group was de-fined, if FeNO level decreased (≧30%) after the treatment, asthma duration was significantly shorter in the responder group than in non-responder group (5.16±3.92 years vs. 21.40±7.79 years, P=0.043). When the FEV1-responder group was defined, if FEV1% increased (≧15%) af-ter the treatment, onset age was significantly lower in the responder group than in the non-responder group (30.0±6.83 years vs. 53.0±16.32years, P=0.008); asthma duration was shorter in the responder group than in the non-responder group. (6.0±5.99 years vs. 16.57±10.23 years, P=0.07). Conclusion: Changes in serum EDN levels may be a potential biomarker for predicting eosinophilic inflammation after anti-IL5 treatment inpatients with SEA, which was affected by patient’ age, onset age and asthma duration.

PE33-6 The effectiveness and safety of one-year use of benralizumab in 19 Japanese patients with severe asthma in clinical practice

Takashi Katsuno, Motoyasu Iikura, Junko Terada, Satoshi Ishi, Eriko Morino, Manabu Suzuki, Shinyu Izumi, Masayuki Hojo, Haruhito Sugiyama(Respiratory Medicine, National Center for Global Health and Medicine, Japan)

Background: Benralizumab, an anti-interleukin (IL)-5Rα antibody, has been available in Japan since 2018 for severe asthmatic patients. Com-pared with other IL-5-targeted antibodies, benralizumab has been known to have a stronger effect on eosinophil depletion. Previous clinical trialsdemonstrated that benralizumab reduced the number of exacerbations and systemic steroid use and improved pulmonary function in severeeosinophilic asthma. In this study, we elucidated the clinical efficacy and safety of benralizumab treatment for one year in Japanese patients withsevere asthma.Methods: The subjects comprised 19 outpatients with severe uncontrolled asthma under the GINA step 4 or 5 treatment. The me-dian age was 68.0 years. The mean values were 481/L for eosinophil counts, 393 IU/mL for IgE levels, and 3.9 times for annual rate of severe exac-erbations. The patients received a subcutaneous injection of benralizumab 30 mg per month for the first 3 months, followed by 30 mg every othermonth. We assessed for asthma control (ACT, ACQ-5); asthma-related QOL (AQLQ); forced expiratory volume in one second (FEV1); symptoms;exhaled nitric oxide (FeNO) level; reduction of systemic steroid use; and adverse events. Results: Of 19 patients followed up after 1 year of treat-ment, there were improvements in ACT from 15.9±6.4 to 20.0±5.63, ACQ-5 from 2.0±1.5 to 0.4±1.11, and AQLQ from 4.1±1.5 to 4.9±1.47, withcomplete depletion of peripheral eosinophils. The FEV1 improved from 1.8±0.56 to 2.4±0.76 L, and FeNO improved from 74.0±53.4 to 54.1±28.8ppb. More than 25% of the reduction of oral prednisone use was observed in 4 patients (57%). In 14 of 17 patients (82%), 1-year benralizumab treat-ment was effective. The adverse events were mild and included pharyngeal discomfort in 3 patients and fatigue in 1 patient. Conclusions: In Japa-nese patients with severe uncontrolled asthma, one-year use of benralizumab is effective in reducing asthma exacerbations and oral corticosteroiduse, and improving asthma control and QOL in clinical practice.

263

PosterSession

PE33-9 Pretreatment serum allergen-specific IgE and omalizumab responsiveness in severe allergic asthma

Tomoko Tajiri, Yoshihiro Kanemitsu, Hirono Nishiyama, Ryota Kurokawa, Norihisa Takeda, Kensuke Fukumitsu, Satoshi Fukuda,Takehiro Uemura, Hirotsugu Ohkubo, Ken Maeno, Yutaka Ito, Masaya Takemura, Akio Niimi (Department of Respiratory Medicine, Allergy andClinical Immunology, Nagoya City University, Graduate School of Medical Sciences, Japan)

Background: Asthma and allergic rhinitis often coexist, and immunoglobulin E (IgE) plays a pivotal role in both the conditions. Omalizumab, a hu-manized anti-IgE monoclonal antibody, has been validated and approved for patients with severe allergic asthma and/or seasonal allergic rhinitis.Sensitization to specific antigens, mainly seasonal allergens, may be predictive of responsiveness to omalizumab. Few studies have reported it. Weassessed whether pretreatment serum allergen-specific IgE could predict responsiveness to omalizumab in patients with severe allergic asthma.Methods: This retrospective study enrolled adult patients with severe allergic asthma who completed a 52-week treatment with omalizumab atNagoya City University Hospital from August 2013 to March 2020. We compared pretreatment serum-specific IgE against pollen, mites, housedust, fungi, and animal dander between responders and non-responders. Response was measured by physicians’ overall assessment at 52 weeks oftreatment. Results:We analyzed 14 patients with severe allergic asthma (10 females, mean (±SD) age of 62±19 years; mean serum total IgE 483±561 IU/mL). Among them, 9 of 14 patients reported comorbid allergic rhinitis (6 cases of seasonal allergic rhinitis). The positive ratio of pretreat-ment pollen-specific IgE was significantly higher in responders than that in non-responders (p=0.04). No significant between-group differenceswere observed for the positive ratio of mite-, house dust-, fungi-, and animal dander-specific IgE between the two patient groups (p>0.10). Five ofsix patients with seasonal allergic rhinitis responded to omalizumab treatment. Conclusions: Pretreatment serum pollen-specific IgE of patientswith severe allergic asthma could be predictive of responsiveness to omalizumab.

PE33-10 Three-year outcomes after bronchial thermoplasty for severe uncontrolled asthmatic patients

Motoyasu Iikura, Keita Sakamoto, Masao Hashimoto, Satoru Ishii, Shinyu Izumi, Masayuki Hojo, Haruhito Sugiyama (Department of RespiratoryMedicine, National Center for Global Health and Medicine, Japan)

Background: Bronchial thermoplasty (BT) has been available as a non-pharmacologic treatment for severe uncontrolled asthma in Japan since2015. Previous trials demonstrated that BT led to improvement of asthma-related quality of life (AQOL), reduction of exacerbation and reductionof systemic steroid use at one year after BT and these effects continued for 3～5 years. In this study we elucidate the long term efficacy andsafety of BT treatment in severe Japanese asthmatic patients in clinical practice. Methods: This study included adult Japanese patients who un-derwent BT for the treatment of severe uncontrolled asthma from Feb 2015 to Feb 2017. All subjects met Global Initiative for Asthma (GINA)definition of severe asthma. We assessed 3-year outcomes after treatment of BT including the asthma control (ACT, ACQ-5), AQLQ, forced expi-ratory volume in one second (FEV1), symptoms, exhaled nitric oxide (FeNO) levels and reduction of systemic steroid use. We also collected the ad-verse events. Results: Sixteen subjects underwent three bronchoscopic procedures for BT. Nine out of 16 patients were followed up for 3 yearsafter BT. The mean age was 60.1 years old, and the average duration of disease was 34.9 years. The mean severe exacerbation rate was 6.4 timesper year under the GINA step 4 or 5 treatments including omalizumab (33%) and oral corticosteroid (OCS) (33%). Sixty-six percentage of reductionof asthma exacerbations was observed at one year after BT and it continued for 3 years (86% reduction). Eight patients (88.9%) had reduced fre-quency of severe exacerbation at 3 years after BT. AQOL and asthma control improved from 1 month until at least 3 years after BT. FEV1 wasslightly increased. Reduction of OCS use was observed in 2 out of 3 patients. Adverse events were mild and occurred within 6 weeks after BTtreatment. Conclusion: BT treatment was a relatively safe procedure that improved asthma control, QOL, along with reduced frequency of se-vere exacerbation in Japanese patients with severe uncontrolled asthma for at least 3 years.

PE33-11 Effect of dupilumab on severe asthma exacerbations in patients with oral corticosteroid-dependent severe asthma with and with-out improvements in lung function

Nicola A Hanania1), Michel Djandji2), Kazuhiko Arima3), Masanori Miyata3), Mario Castro4), Nadia Daizadeh2), Benjamin Ortiz5) (Baylor College ofMedicine, USA1); Sanofi U.S., USA2); Sanofi K.K., Japan3); University of Kansas School of Medicine, USA4); Regeneron Pharmaceuticals, Inc., USA5))

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key and centraldrivers of type 2 inflammation in multiple diseases. In phase 3, LIBERTY ASTHMA VENTURE study (NCT02528214), add-on dupilumab 300mgevery 2 weeks vs placebo reduced oral corticosteroid (OCS) maintenance dose, rate of severe asthma exacerbations, and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1), independently of baseline eosinophil levels, in patients with OCS-dependent, severeasthma. Dupilumab was generally well tolerated in these patients. This post hoc analysis assessed the effect of dupilumab treatment on severeasthma exacerbations in patients with OCS-dependent, severe asthma with and without clinically meaningful improvements in pre bronchodilatorFEV1 at Weeks 2 and 12. Methods: Annualized rates of severe asthma exacerbations during the 24-week treatment period in patients with andwithout improvements of 100mL or 200mL in pre bronchodilator FEV1 at Weeks 2 and 12 were analyzed using a negative binomial regressionmodel. Results: Of dupilumab- (n=103)/placebo-treated (n=107) patients, the total number of patients achieving 100mL and 200mL improvementsin pre-bronchodilator FEV1 were 63/29 and 47/21 at Week 2, and 65/35 and 49/25 at Week 12, respectively. In patients achieving 100mL and 200mL improvements in pre-bronchodilator FEV1 at Week 2, dupilumab vs placebo significantly reduced severe exacerbations during the 24-weektreatment period by 69.6% (P<0.001) and 71.9% (P=0.001), respectively, and by 71.9% (P<0.0001) and 67% (P<0.01) in patients achieving 100mL and200mL improvements, at Week 12. Dupilumab vs placebo numerically decreased severe exacerbations by 46.8% (P=0.06) and 47.9% (P<0.05) in pa-tients failing to achieve 100mL and 200mL improvements in pre bronchodilator FEV1 at Week 2, and by 42.2% (P=0.11) and 56.6% (P<0.01) atWeek 12. No significant interaction was identified between treatment and the subgroups of patients with and without improvements in lung func-tion at Week 2 and Week 12. Conclusion: Dupilumab vs placebo reduced severe exacerbations during the 24-week treatment period in OCS-dependent, severe asthma patients, particularly in patients with improvements in lung function at Weeks 2 and 12.

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PosterSession

PE33-12 Treatment effects and safety of bronchial thermoplasty based on multicenter research in Japan

Akihiro Takemasa1), Nobuhiko Uchida1), Yusuke Nakamura1), Kazuyuki Chibana1), Yasuo Shimizu1), Tamotsu Ishizuka2), Ken Ohta3),Haruhito Sugiyama4), Akio Niimi5), Tomohisa Baba6), Masamichi Mineshita7) (Department of Pulmonary Medicine and Clinical Immunology, DokkyoMedical University School of Medicine, Japan1); Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui Respira-tory Disease Center, Japan2); Fukujuji Hospital, Japan Anti-Tuberculosis Association, Japan3); Department of Respiratory Medicine, National Cen-ter for Global Health and Medicine, Japan4); Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City UniversityGraduate School of Medical Sciences, Japan5); Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan6);Division of Respiratory Diseases, Department of Internal Medicine, St. Marianna University School of Medicine, Japan7))

Background: There are no clinical trials of bronchial thermoplasty (BT) in Japan, and there are no data on efficacy and safety for Japanese. Wehave collected cases from multiple centers for cases that have already undergone BT, and have retrospectively analyzed and studied the thera-peutic effects and safety.Methods: The subjects who underwent BT from January 1, 2015 to December 30, 2019 were targeted. We conducted amulticenter cohort study on efficacy and safety endpoints. Results: Interim analysis was performed for 116 registered cases (42 males and 74 fe-males) among 30 participating facilities and 294 cases to be registered. The average age of the subjects was 52.3 years (18-78), and 38.3% of pa-tients used biological drugs (Bio) before and after BT. Bio was discontinued after BT treatment in more than one-fifth of the cases where Bio wereintroduced before BT. Significant improvements in AQLQ were observed in cases where Bio was introduced after BT, and in cases where Biowas continuously used after BT. Conclusion: It is suggested that BT can be expected to have a certain effect in the patients where Bio is needed.We will report details regarding efficacy and safety.

PE33-13 The relationship between the effectiveness of anti-IL-5 antibodies and mucous plugs in severe asthma

Satoshi Marumo, Yusuke Hayashi, Yusuke Shiraishi, Takamasa Kitajima, Daiki Inoue, Motonari Fukui (Department of Respiratory Medicine, Ki-tano Hospital, Japan)

Background:Mucus plugs of severe asthmatic patients have been shown to contribute eosinophilic airway inflammation and airflow obstruction.Anti-IL-5 antibodies (Mepolizumab and Benralizumab) suppress airway eosinophilic inflammation and improve airflow obstruction in severeasthma. In the present study, we investigated the relationship between mucus plugs and the effects of anti-IL-5 antibodies in severe asthma.Methods: Severe asthmatic patients with screening chest CT scan before administration of anti-IL-5 antibodies were included into the retrospec-tive cohort study at our hospital. Mucus plugs score was calculated using chest CT. We compared the effectiveness of anti-IL-5 antibodies byeosinophilic inflammation (FeNO), airflow obstruction (spirometry), symptoms (Asthma Control Test [ACT]), and exacerbation rates among pa-tients with or without mucus plugs. Results: Thirty-four cases were included into the final analysis. There were no significant difference in the ef-fectiveness of anti-IL-5 antibodies with or without mucus plugs. Administration of anti-IL-5 antibodies improved symptoms and eosinophilic in-flammation more significantly in patients with high mucus scores than with low mucus scores. Conclusions: The effectiveness of anti-IL-5 anti-bodies did not differ with or without mucus plugs among severe asthmatic patients. Further studies are needed to confirm whether the degree ofmucus plugs determines the effectiveness of biologics.

PE33-14 Biological agents for severe asthma: a retrospective study of clinical utility and safety from real-world experience

Seigo Katakura1), Nobuaki Kobayashi1), Wataru Hashimoto1), Katushi Tanaka1), Ryo Nagasawa1), Ko Chin1), Ayako Aoki1), Kentaro Nakashima1),Shuhei Teranishi1), Hiroki Watanabe1), Keisuke Watanabe1), Yu Hara1), Masaki Yamamoto2), Makoto Kudo2), Takeshi Kaneko1) (Department of Pul-monology, Yokohama City University Graduate School of Medicine, Japan1); Respiratory Disease Center, Yokohama City University Medical Cen-ter, Japan2))

Background: Biological agents that block the Th2 inflammation pathway are the keys to personalized medicine against moderate-to-severe bron-chial asthma. They have drastically changed the treatment for severe asthma in clinical trials, but real-world evidence is lacking. This study wasconducted to evaluate the efficacy and adverse events of biological agents against severe asthma in clinical settings. Method: A total of 80 adultpatients who had been administered biological agents for refractory asthma between January 2012 and March 2019 at Yokohama City UniversityHospital and Yokohama City University Medical Center were included in this retrospective study. The outcomes, such as the number of emer-gency room (ER) visits due to asthma attacks 1 year before and after introduction of biological agents, administration period of biological agents,peripheral blood eosinophil count, IgE value, respiratory function test results, FeNO test results, and adverse events were identified from themedical records and statistically analyzed. Results: The proportions of biological agents were 29.8% for malizumab, 24.6% for mepolizumab, 36.8%for benralizumab, and 8.8% for dupilumab. Frequency of ER visits due to asthma attacks were reduced in 34 out of 50 patients (68.0%) who hadbeen receiving biological agents for more than 1 year compared with the previous year. The dose of oral corticosteroid after treatment with bi-ologics was reduced in 40% of the cases. Adverse events occurred in 18 cases (15.8%), and Grade 3 or higher adverse events were observed in 2cases (1.8%). Owing to long-term efficacy, 9 patients (7.9%) discontinued biological agents, and 7 of them did not have asthma attacks for 1 year af-ter discontinuation. Conclusion: In clinical practice, the majority of patients with severe asthma are safely treated with biologics because adverseevents are rare. Favorable responses were obtained in 68% of the patients. Patients who responded to biological agents for a long term were lesslikely to experience exacerbation after discontinuation of biological agents.

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PosterSession

PE33-15 Clinical features and effects of biologic agents for severe asthma

Kaori Okayasu1), Harumi Sano2), Natsumi Asao2), Koki Hata2), Toshihisa Ishikawa2), Reina Imase2), Juri Honda2), Tsutomu Kawasaki2),Yukiko Yamashita3), Naoto Watanabe1), Yoichi Nakamura1), Yasunari Miyazaki4) (Medical Center for Allergic and Immune Diseases, YokohamaCity Minato Red Cross Hospital, Japan1); Department of Respiratory Medicine, Yokohama City Minato Red Cross Hospital, Japan2); Department ofOtorhinolaryngology, Yokohama City Minato Red Cross Hospital, Japan3); Department of Respiratory Medicine, Tokyo Medical and Dental Uni-versity, Japan4))

Background: In Japan, 4 biological agents have been approved for the management of severe uncontrolled asthma. It is still under discussionwhich biologic treatment will be appropriate to the patient and be continuable. The aim of the study is to clarify the predictor on the efficacy ofthe biologics. Methods: We conducted a retrospective analysis of clinical features in severe asthma patients who received biologic treatments(Anti-IgE, Anti-IL5/anti-IL-5R, Anti-IL4R) from September 2013 to February 2020 in Yokohama City Minato Red Cross Hospital. Clinical featuresincluding phenotypic information were assessed at the time of the start and the end of treatment, or that in February 2020. We also assessed sev-eral factors associated with improvement and long-term sustainability. Results: Thirty-seven cases (mean 60.3±14.0 years old, M:F 17:20, GINAstep 5:4 11:16) treated with biologic treatments were enrolled. Eight cases were treated with different types of biologic agents by switching. Sixcases had eosinophilic chronic rhinosinusitis as co-morbid. Eleven cases were treated with omalizumab, and 8 with mepolizumab, 10 with benrali-zumab, 8 with dupilumab, respectively. Biologic treatments were clinically effective in 24 cases (64.9%) and maintenance oral corticosteroid couldbe reduced in 12 cases (32.4%). They also reduced asthma exacerbations in 20 cases (54.1%). Among those biologic agents, there was no signifi-cance in the effectiveness or the rate of reduction in exacerbations. Blood eosinophil counts were significantly decreased with biologic treatments(median 270 to 31/l, p=0.0012), however, other markers (total IgE, FEV1, FeNO, ACT scores) did not show significant change. In 24 cases treatedwith biologics for more than 10 times (64.9%), the FEV1 before the treatment of biological agents was significantly lower than that of the casestreated less than 10 times. None of blood eosinophil counts, IgE, FeNO, FEV1, or ACT scores were correlated with the improvement. Conclusion:Prediction of the efficacy of biologic agents in each case of severe-asthma patient is under discussion. However, severe asthmatics with low FEV1may have benefits by biologic treatment for long periods.

PE33-16 Effectiveness and safety of dupilumab for severe asthmatic patients in clinical practice

Motoyasu Iikura, Junko Hirashima, Shinyu Izumi, Masayuki Hojo, Haruhito Sugiyama (Department of Respiratory Medicine, National Center forGlobal Health and Medicine, Japan)

Rationale: Dupilumab, anti-IL-4R antibody, has been available for severe asthmatic patients in Japan since 2019. This antibody has been also avail-able for patients with atopic dermatitis or chronic sinusitis with nasal polyps. Previous clinical trials demonstrated that dupilumab reducedasthma exacerbation, reduced systemic steroid use, improved asthma control, and improved pulmonary function including forced expiratory vol-ume in one second (FEV1) and exhaled nitric oxide (FeNO). In this study we elucidate the efficacy and safety of dupilumab in severe Japaneseasthmatic patients in clinical practice.Methods: Subjects were 10 severe uncontrolled asthmatic patients under the GINA step 4 or 5 treatmentsincluding oral corticosteroid (OCS) use (60%), or prior treatments of omalizumab (50%), mepolizumab (10%), benralizumab (20%) or bronchial ther-moplasty (40%) in our outpatient clinic. The mean age was 49 years old, and the average duration of disease was 40 years. The mean eosinophilcount was 278/µl and the mean IgE level was 653 IU/ml. The mean severe exacerbation rate was 4.2 times per year. They were received subcu-taneous injection of dupilumab 300 mg every 2 weeks. We assessed the asthma control (ACT, ACQ-5), asthma-related QOL (AQLQ), FEV1, symp-tom, FeNO level and reduction of OCS use after-treatment of dupilumab. We also collected the adverse events in these patients. Results: Aftersix-month treatment, ACT score improved from 14 to 18, and ACQ-5 improved from 2.4 to 1.7, and AQLQ improved from 4.3 to 5.1. FEV1 in-creased from 2.40 to 2.61 L. FeNO level decreased from 23.0 to 17.3 ppb. Reduction of regular OCS use was observed in 3 out of 6 patients. De-creased exacerbation was observed in five patients who had experienced at least one exacerbation per year. Improvement of skin itching was ob-served in 7 patients who had atopic dermatitis. Conjunctivitis was observed in one patient for adverse event. Conclusions: Treatment of dupi-lumab improved asthma control, QOL, pulmonary function and reduction of OCS use and reduction of exacerbation in patients with severe uncon-trolled asthma in clinical practice.