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Barnes-Jewish Hospital andWashington University Physicians
New Directions in COPD, ACO and the
Chronic Airflow Obstruction Phenotype Mario Castro MD, MPH
Asthma & Airway Translational Research UnitWashington University School of Medicine
St. Louis, Missouri, USA
DISCLOSURES
• Speaker; Honorarium- Boehinger Ingelheim - Genentech- AstraZeneca - Teva- Boston Scientific
•Principal Investigator; Contracted Research- Boehinger Ingelheim - Vectura- Chiesi - ALA- Sanofi-Aventis - NIH
DISCLOSURES (cont.)
• Consultant; Consulting fee - Nuvaira - Sanofi-Aventis- Aviragen - Teva- Genentech - Theravance- Neutronic - Vectura
• Author; Royalties- Elsevier
• Co-Investigator; Contracted Research- NIH - PCORI
LEARNING OBJECTIVES
• Define the current definitions of COPD and ACOS
• Interpret the current GOLD classification and treatment for patients with COPD
• Discuss therapeutic approaches to the chronic airflow obstruction phenotype
COPD Is a Major Public Health Problem and Leading Cause of Disability
• More than 20 million Americans have COPD1
• COPD prevalence is 6% (females > males)- 12.7 million diagnosed and 12 million undiagnosed- Asthma prevalence is 8% (28 million) - NHANES
• Chronic lower respiratory disease (COPD) is now the third leading cause of death (surpassing stroke)
• Second leading cause of disability (first is heart disease)
• 70% of patients are <65 years old
Prevalence - COPD►Estimated 384 million COPD cases in 2010.
►Estimated global prevalence of 11.7% (95% CI 8.4%–15.0%).
►Three million deaths annually.
►With increasing prevalence of smoking in developing countries, and aging populations in high-income countries, the prevalence of COPD is expected to rise over the next 30 years.
►By 2030 predicted 4.5 million COPD related deaths annually.
Cosio M et al. N Engl J Med 2009;360:2445-2454
Specimens from the Small Airways in the Healthy Lung of a Nonsmoker and the Lung of a Smoker
with COPD
Exacerbations Contribute to the Cycle of Decline in COPD
Reduced exercise endurance
Dyspnea
Activity limitation
Poor health-related quality of life
Deconditioning
ExacerbationsAir trapping
Expiratory flow limitation
Hyperinflation
Exacerbations become more frequent and more severe as the severity of underlying COPD increases1-3
8
FEV1=forced expiratory volume in the first second. Figure reproduced with permission. Copyright © 2008 Informa Healthcare.11. Decramer M et al. COPD. 2008;5(4):235-256; 2. Cooper CB. Am J Med. 2006;119(10 suppl 1):21-31; 3. Hurst JR et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. N Engl J Med. 2010;363(12):1128-1138.
IRV
FRC=functional residual capacity; IC=inspiratory capacity; IRV=inspiratory reserve volume; RV=residual volume; TLC=total lung capacity; VC=vital capacity; VT =tidal volume.
Ferguson GT. Proc Am Thorac Soc. 2006;3:176-179.Modified with permission of the American Thoracic Society. Copyright © 2016 American Thoracic Society.
The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
9
Lung Volumes Can Be Altered in COPD Patients Both at Rest and During Exercise
Healthy
Patients
Patients With COPD
FRC
FRC
IRV
IRV
Lung
Vol
ume
Maximum
inspiration
IC
Maximum exhalation
VC
TLCVT
RV
IC
IC
Healthy Patients During
Activity
Patients With COPD During
Activity
140120100806040200
140
4020
80
100
120
60
0
0 020
20
40
40
60
60
80
80
Minute Ventilation (L/min)1
Volu
me
(% p
redi
cted
TLC
)
VT
VT
FRC
Dynamic changes in lung volumes during exercise in
normal lungs and COPD
During exercise (dynamic)
VT
VT
Lung volume measurements
FRC
10
1. Cooper CB. Am J Med. 2006;119(10 suppl 1):S21-S31.
2. Ferguson GT. Proc Am Thorac Soc. 2006;3:176-179.
Dynamic Hyperinflation Links to Dyspnea and Activity Limitations in COPD1,2
Dynamic hyperinflation occurs
when patients commence inhalation before full exhalation has been achieved. Consequently, air is
trapped within the lungs with each successive
breath.2
Adapted with permission from Cooper, Am J Med. 2006 (Figure 3).
COPDAirflow
Obstruction
Air Trapping
Dynamic Hyperinflati
on
Poor Health-Related Quality of Life
Patient-centered Outcome
s
Tachypnea
Dyspnea
↑ Ventilatory Requireme
nt
Activity Limitation
DeconditioningAnxiety
Increased work of
breathing
11
Hyperinflation Explained Physical Inactivity Better Than FEV1
• Study examined the contribution of dynamic hyperinflation to limitations in activities of daily living in COPD patients
• For a given FEV1 range, as characterized by GOLD stage, there was variance in daily physical activity
• Using multiple regression, FEV1did not independently correlate with variance in activity (P=0.939)
• Percent change in inspiratory capacity predicted variance in activity (P=0.046)
VMU=vector magnitude units.Lahaije AJ, et al. Respiratory Medicine.
2013;107:834-840.
P<0.0001 for linear trend (N=57)
46% of variance in physical activity was explained by difference in the
degree of hyperinflation
Daily
Phy
sica
l Act
ivity
(VM
U)
Symptom assessment► COPD Assessment Test (CAT TM )
► Chronic Respiratory Questionnaire (CCQ® )► St George’s Respiratory Questionnaire (SGRQ)
► Chronic Respiratory Questionnaire (CRQ)► Modified Medical Research Council (mMRC) questionnaire
GOLD 2018 Algorithm for Assessingthe Clinical Severity of COPD
13
CAT=COPD Assessment TestTM; mMRC=modified Medical Research Council Dyspnea Scale.International Journal of Chronic Obstructive Pulmonary Disease by DOVE Medical Press. Reproduced with permission of DOVE Medical Press in the format Republish in presentation/slides via Copyright Clearance Center. From the Global Strategy for Diagnosis, Management and Prevention of COPD 2015, © Global Initiative for Chronic Obstructive Lung Disease (GOLD), all rights reserved. Available from http://www.goldcopd.org.
GROUPC-HighRisk,LessSymptoms
GROUPD-HighRisk,MoreSymptoms
GROUPA-LowRisk,LessSymptoms
GROUPB-LowRisk,MoreSymptoms
SymptomsCAT<10 CAT≥10
RISK
GOLD
Classificatio
nof
AirflowLim
itatio
n
RISK
Exacerbatio
nHistory
1notleadingtohospitaladmission
0
(C) (D)
(B)(A)
≥2or≥1leadingtohospitaladmission
mMRC0-1 mMRC≥2
Breathlessness
4
3
2
1
Pharmacologic Therapy
© 2017 Global Initiative for Chronic Obstructive Lung Disease
Pharmacologic Therapy
© 2017 Global Initiative for Chronic Obstructive Lung Disease
Bronchodilators in Stable COPD
© 2017 Global Initiative for Chronic Obstructive Lung Disease
Anti-inflammatory Therapy in Stable COPD
© 2017 Global Initiative for Chronic Obstructive Lung Disease
18
Initial Pharmacological Management of COPD Recommended by GOLD 2018
Question 1
Patient with FEV1 of 55% (FEV1/FVC = 0.62), 2 prior hospitalizations for COPD, mMRC score of 3, on budesonide/formoterol.
Which of the following is the correct GOLD group?A.Group AB.Group BC.Group CD.Group D
Question 2
Patient from Prior Question. Based on their Group, what pharmacologic treatment?
A. Roflumilast onlyB. High dose ICS onlyC. LAMA or LABA monotherapyD. Continue LAMA/LABA combo onlyE. Continue ICS/LABA, add LAMA +/- roflumilast
Patient RecommendedFirst choice
Alternative choice Other PossibleTreatments
D
ICS + LABAand/orLAMA
ICS + LABA and LAMA orICS+LABA and PDE4-inh. or
LAMA and LABA orLAMA and PDE4-inh.
CarbocysteineN-acetylcysteine
SABA and/or SAMATheophylline
Question 2
SVC=slow vital capacity; UPLIFT=Understanding Potential Long-Term Impacts on Function with Tiotropium.Tashkin DP et al; for the UPLIFT Study Investigators. N Engl J Med. 2008;359(15):1543-1554; Data on file, Boehringer Ingelheim Pharmaceuticals, Inc.Please see full Prescribing Information and Important Safety Information available at this presentation.
Follow-up(30 days)
Run-in(2 weeks)
Treatment period(48 months)
SPIRIVA HandiHaler, n=2986
Months 0.5 48 49Randomization
Control, n=3006
Secondary endpoints included:• Yearly rate of decline in pre- and
postbronchodilator FEV1, FVC, and SVC from Day 1 until 1 month after end of study drug administration
• Yearly rate of decline in pre- and postbronchodilator FVC and SVC from Day 30 until completion of study
• Exacerbations and related hospitalizations
Screening
Coprimary endpoints:• Yearly rate of
decline in mean FEV1(prebronchodilator)
• Yearly rate of decline in mean FEV1(postbronchodilator)
UPLIFT Clinical Study Design: 4-Year Efficacy and Safety Trial in Patients With COPD
22
UPLIFT Trial: Tiotropium Improved FEV1 vs Control and Sustained the Difference Over 4 Years
Tashkin DP et al N Engl J Med. 2008;359(15):1543-1554.
* Exacerbations were defined as an increase in or the new onset of more than one respiratory symptom (cough, sputum, sputum purulence, wheezing, or dyspnea) lasting 3 days or more and requiring treatment with an antibiotic and/or a systemic corticosteroid.CI=confidence interval; HR=hazard ratio.Tashkin DP et al; for the UPLIFT Study Investigators. N Engl J Med. 2008;359(15):1543-1554.Please see full Prescribing Information and Important Safety Information available at this presentation.
UPLIFT Trial: Reduction in Exacerbations*
24
Secondary Endpoint SPIRIVA vs Control
Risk of Exacerbations• Reduced the risk of exacerbations versus
control by 14%• Mean number of exacerbations per patient-year was 0.73 vs 0.85, respectively
(HR 0.86; 95% CI, 0.81-0.91, P<.001 )
Median Timeto First Exacerbation
• Delayed median time to first COPD exacerbation versus control by 33% (4.2 months)
• Median time to first COPD exacerbation for SPIRIVA was 16.7 months (95% CI, 14.9-17.9) vs 12.5 months for control (95% CI, 11.5-13.8)
Exacerbations Leading to Hospitalization
• Reduced the risk of hospitalization associated with exacerbations versus control by 14%
• HR 0.86; 95% CI, 0.78-0.95; P=.002
SPIRIVA did not slow the yearly rate of decline in pre- and postbronchodilator FEV1vs control, which were the coprimary endpoints of the study (P=NS).
Nonpharmacologic Therapyto Manage COPD
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2008. http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed November 21, 2008.
Patient Education
Oxygen TherapySurgical and Non-
surgical AlternativesPulmonary
Rehabilitation
Smoking Cessation Vaccination
• ¼th of patients with COPD report a history of asthma
• Asthma and COPD have common origins (“Dutch hypothesis”)
• In patients with chronic airways disease, the differential diagnosis differs by age- Children and young adults: most likely to be asthma- Adults >40 years: COPD becomes more common, and
distinguishing asthma from COPD becomes more difficult
• Many patients with symptoms of chronic airways disease have features of both asthma and COPD- This has been called asthma-COPD overlap (ACO)
Asthma COPD Overlap
• Patients with features of both asthma and COPD have worse outcomes than those with asthma or COPD alone- Frequent exacerbations- Poor quality of life- More rapid decline in lung function- Higher mortality- Greater health care utilization
• Rates of overlap between15–55% of patients with chronic airways disease, depending on the definitions and population
Asthma-COPD overlap
Major and Minor CriteriaUsed to Define ACO
Major Criteria Minor CriteriaPrevious history of asthma (before age 40)
IgE > 100 IU, or
Bronchodilator response to salbutamol > 15% and 400 mL
History of atopy,
Sputum eosinophils 2 separated bronchodilator responses to salbutamol > 12% and 200 mL
{Blood eosinophils > 5%}*
Soler-Catalonia et al Archivos Bronconeumologia 2012; *Cosio et al. CHEST 2016 149, 45-52
• Distinguishing asthma from COPD can be problematic- Particularly in smokers and older adults- Some patients may have clinical features of both asthma and COPD
• Most clinical trials and guidelines are about asthma or COPD alone
• The descriptive term asthma-COPD overlap (ACO) is useful - It maintains awareness by clinicians, researchers and regulators of the
needs of these patients• “Asthma-COPD overlap” is not a single disease entity
- As for asthma and COPD, it includes patients with several different forms of airways disease (phenotypes)...
- These features are caused by a range of different underlying mechanisms • To avoid the impression that this is a single disease, the
previous term Asthma COPD Overlap Syndrome (ACOS) is no longer advised.
Asthma-COPD overlap– change in terminology
GINA 2017
• Of 10,192 pts in the COPDGene Study with history of smoking, 385 met criteria for ACOS-bronchodilator responsiveness:- history of asthma or hay fever, - the presence of airway obstruction with significant
bronchodilator responsiveness, and - minimal (<15%) emphysema present on CT
• More likely to be younger, African American, higher BMI, and current smokers
• Majority GOLD grade B• More likely to experience severe & and
frequent exacerbations (adjusted analysis)
Defining Asthma-COPD Overlap (ACO)
Cosentino J, and COPDGene Investigators. Ann Am Thorac Soc 2016;13:1483–1489.
Defining Asthma-COPD Overlap (ACO)
Cosio et al. CHEST 2016 149, 45-52DOI: (10.1378/chest.15-1055)
• 831 patients with COPD at 36 sites in Spain in the COPD History Assessment in Spain (CHAIN) cohort
• assumed that all the patients fulfill 3 or more of the usual features of COPD: age > 40 years, postbronchodilator FEV1/FVC < 0.7, and exposure to cigarette smoke.
• Of 125 (15%) fulfilled the criteria for ACOS, and 98.4% of them sustained these criteria after 1 year.
Definitions
GINA 2017, Box 5-1 (3/3)
AsthmaAsthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation. [GINA 2017]
COPDChronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. [GOLD 2017]
Asthma-COPD overlap [not a definition, but a description for clinical use]Asthma-COPD overlap (ACO) is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. Asthma-COPD overlap is therefore identified in clinical practice by the features that it shares with both asthma and COPD.This is not a definition, but a description for clinical use, as asthma-COPD overlap includes several different clinical phenotypes and there are likely to be several different underlying mechanisms.
• Clinical history: consider chronic airways disease if- Chronic or recurrent cough, sputum, dyspnea or wheezing, or
repeated acute lower respiratory tract infections- Previous doctor diagnosis of asthma and/or COPD- Previous treatment with inhaled medications- History of smoking tobacco and/or other substances- Exposure to environmental hazards, e.g. airborne pollutants
• Physical examination- May be normal- Evidence of hyperinflation or respiratory insufficiency- Wheeze and/or crackles
Step 1 – Does the patient have chronic airways disease?
GINA 2017
• Radiology (CXR or CT scan performed for other reasons)
- May be normal, especially in early stages- Hyperinflation, airway wall thickening,
hyperlucency, bullae- May identify or suggest an alternative or additional
diagnosis, e.g. bronchiectasis, tuberculosis, interstitial lung disease, cardiac failure
• Screening questionnaires- Designed to assist in identification of patients at
risk of chronic airways disease- May not be generalizable to all countries, practice
settings or patients
Step 1 – Does the patient have chronic airways disease?
GINA 2017
• Assemble the features that, when present, most favor a diagnosis of typical asthma or typical COPD
• Compare the number of features on each side- If the patient has ≥3 features of either asthma or COPD,
there is a strong likelihood that this is the correct diagnosis• Consider the level of certainty around the diagnosis
- Diagnoses are made on the weight of evidence- The absence of any of these features does not rule out either
diagnosis, e.g. absence of atopy does not rule out asthma- When a patient has a similar number of features of both
asthma and COPD, consider the diagnosis of asthma-COPD overlap
Step 2 – Syndromic diagnosis of asthma, COPD and asthma-COPD overlap
GINA 2017
© Global Initiative for AsthmaGINA 2014 © Global Initiative for AsthmaGINA 2017, Box 5-4
SYNDROMIC DIAGNOSIS IN ADULTS(i) Assemble the features for asthma and for COPD that best describe the patient.(ii) Compare number of features in favour of each diagnosis and select a diagnosis
STEP 2
Features: if present suggest - ASTHMA COPDAge of onset q Before age 20 years q After age 40 years
Pattern of symptoms q Variation over minutes, hours or days
q Worse during the night or early morning
q Triggered by exercise, emotionsincluding laughter, dust or exposure
to allergens
q Persistent despite treatment
q Good and bad days but always dailysymptoms and exertional dyspnea
q Chronic cough & sputum preceded onset of dyspnea, unrelated to triggers
Lung function q Record of variable airflow limitation(spirometry or peak flow)
q Record of persistent airflow limitation(FEV1/FVC < 0.7 post-BD)
Lung function betweensymptoms
q Normal q Abnormal
Past history or family history q Previous doctor diagnosis of asthma
q Family history of asthma, and other allergic conditions (allergic rhinitis or
eczema)
q Previous doctor diagnosis of COPD,chronic bronchitis or emphysema
q Heavy exposure to risk factor: tobaccosmoke, biomass fuels
Time course q No worsening of symptoms over time.Variation in symptoms either
seasonally, or from year to yearq May improve spontaneously or have
an immediate response to bronchodilators or to ICS over weeks
q Symptoms slowly worsening over time(progressive course over years)
q Rapid-acting bronchodilator treatmentprovides only limited relief
Chest X-ray q Normal q Severe hyperinflation
DIAGNOSIS
CONFIDENCE INDIAGNOSIS
Asthma
Asthma
Some featuresof asthma
Asthma
Features of both
Could be ACO
Some featuresof COPD
Possibly COPD
COPD
COPD
NOTE: • These features best distinguish between asthma and COPD. • Several positive features (3 or more) for either asthma or COPD suggestthat diagnosis. • If there are a similar number for both asthma and COPD, consider diagnosis of ACO
• Essential if chronic airways disease is suspected- Confirms chronic airflow limitation- More limited value in distinguishing between asthma with
fixed airflow limitation, COPD and asthma-COPD overlap• Measure at the initial visit or subsequent visit
- If possible measure before and after a trial of treatment- Medications taken before testing may influence results
• Peak expiratory flow (PEF) - Not a substitute for spirometry- Normal PEF does not rule out asthma or COPD- Repeated measurement may confirm excessive variability,
found in asthma or in some patients with asthma-COPD overlap
Step 3 - Spirometry
GINA 2017, Box 5-3
© Global Initiative for Asthma
Step 3 - Spirometry
Spirometric variable Asthma COPD Overlap
Normal FEV1/FVCpre- or post-BD
Compatible with asthma Not compatible withdiagnosis (GOLD)
Not compatible unlessother evidence of chronic
airflow limitation
FEV1 ≥80% predicted Compatible with asthma(good control, or interval
between symptoms)
Compatible with GOLDcategory A or B if post-
BD FEV1/FVC <0.7
Compatible with mildACO
Post-BD increase in FEV1 >12% and 400mL
from baseline
- High probability ofasthma
Unusual in COPD.Consider ACO
Compatible withdiagnosis of ACO
Post-BD FEV1/FVC <0.7- Indicates airflowlimitation; may improve
Required for diagnosisby GOLD criteria
Usual in asthma-COPD overlap (ACO)
Post-BD increase in FEV1 >12% and 200mLfrom baseline (reversible
airflow limitation)
- Usual at some time incourse of asthma; not
always present
Common in COPD andmore likely when FEV1
is low
Common in ACO, andmore likely when FEV1 is
low
FEV1<80% predicted Compatible with asthma.A risk factor for exacerbations
Indicates severity ofairflow limitation and risk
of exacerbations and mortality
Indicates severity ofairflow limitation and risk
of exacerbations and mortality
GINA 2017, Box 5-3
• Initial pharmacotherapy choices are based on both efficacy and safety• If syndromic assessment suggests asthma as single diagnosis
- Start with low-dose ICS- Add LABA and/or LAMA if needed for poor control despite good adherence
and correct technique- Do not give LABA alone without ICS
• If syndromic assessment suggests COPD as single diagnosis- Start with bronchodilators or combination therapy- Do not give ICS alone without LABA and/or LAMA
• If differential diagnosis is equally balanced between asthma and COPD, i.e. asthma-COPD overlap- Start treatment as for asthma, pending further investigations- Start with ICS at low or moderate dose- Usually also add LABA and/or LAMA, or continue if already prescribed
Step 4 – Commence initial therapy
• For all patients with chronic airflow limitation: - Treat modifiable risk factors including advice about
smoking cessation- Treat comorbidities- Advise about non-pharmacological strategies
including physical activity, and, for COPD or asthma-COPD overlap, pulmonary rehabilitation and vaccinations
- Provide appropriate self-management strategies- Arrange regular follow-up
Step 4 – Commence initial therapy
© Global Initiative for Asthma
Investigation Asthma COPDDLCO Normal or slightly elevated Often reducedArterial blood gases Normal between
exacerbationsIn severe COPD, may be abnormal between exacerbations
Airway hyperresponsiveness
Not useful on its own in distinguishing asthma and COPD. Higher levels favor asthma
High resolution CT scan
Usually normal; may show air trapping and increased airway wall thickness
Air trapping or emphysema; may show bronchial wall thickening and features of pulmonary hypertension
Tests for atopy(sIgE and/or skin prick tests)
Not essential for diagnosis; increases probability of asthma
Conforms to background prevalence; does not rule out COPD
FENO If high (>50ppb) supports eosinophilic inflammation
Usually normal. Low in current smokers
Blood eosinophilia Supports asthma diagnosis May be found during exacerbations
Sputum inflammatory cell analysis
Role in differential diagnosis not established in large populations
Step 5 – Refer for specialized investigations if needed
GINA 2017, Box 5-5
Question 3• A 55 y.o. Caucasian female presents to your office for evaluation of
cough and recurring “bronchitis”. She informs you that over the last 3 winters, she has always needed 2 courses of antibiotics for “bronchitis that settled into my chest and won’t go away”. The last episode has left her a little winded climbing stairs, but she also attributes that to her lack of exercise and weight gain since she quit smoking at age 38 (started age 16 1 ppd). FH pertinent for mother had asthma, and that patient reports that she had asthma as a child with symptoms disappearing at about age 14. Blood work demonstrates a serum IgE of 214 (normal < 100) and a peripheral eosinophil count of 435. Spirometry demonstrates an FEV1 60% pred anc FEV1/FVC ratio of 65%. The best diagnosis is:
A. Severe persistent asthmaB. COPD, category AC. Asthma - COPD overlapD. Eosinophilic bronchitis
Characteristic Associations Specifically-targeted treatmentsSevere allergic asthma
High eosinophilHigh serum IgEHigh FeNO
Anti-IgE (adults & children)Anti-IL4/IL-13IL4 Receptor
Eosinophilic asthma High serum IgERecurrent exacerbationsHigh FeNO
Anti-IL5Anti-IL-4/-13 IL-4R
Non-eosinophilic, neutrophilic asthma
Corticosteroid insensitivityBacterial infections
Anti-IL-8CXCR2 antagonistsAnti-LTB4 (adults and children)Macrolides (adults and children)
Chronic airflow obstruction
Airway wall remodelling as increased airway wall thickness
Anti-IL13Bronchial thermoplasty
Recurrent exacerbations
Eosinophils in sputumReduced response to ICS ±OCS
Anti-IL5Anti-IgE (adults and children)
Corticosteroid insensitivity
High neutrophils in sputum2 p38 MAPK inhibitorsTheophylline (adults and children)Macrolides (adults and children)
Potential phenotype-targeted therapiesin severe asthma
International ERS/ATS GUIDELINES Eur Respir J, 2014; 43(2):343-373
Early onset asthma (EOA); Normal lung function; Atopic≤ 2 Controller (medication use); Minimal Health Care
Utilization (HCU); sputum eosinophils (EOS)
Most common cluster; EOA; Borderline normal FEV1 but reverses to normal; Atopic; ≤ 2 Controllers; Very low HCU,
but some oral steroid bursts (OCS); sputum eosinophils
Older; Late onset (LOA); higher BMI; Less atopic; Moderately low FEV1 with some reversibility; Higher dose ICS; ≥ 3 Controllers, but despite this more OCS bursts; increased sputum eosinophils
EOA; 53% male; Severely decreased FEV1, but very reversible to near normal; Atopic; ”Variable” with need for frequent OCS; High
beta agonist use, HCU and symptoms; increased sputum EOS
Older; long duration; 63% female; higher BMI; GERD; HTN,; Less atopic; Severely decreased FEV1 less reversibility; On OCS; High beta-agonist use, HCU, symptoms; increased sputum PMN, EOS)
2 Mild-Moderate Allergic Asthma
3 More SevereOlder Onset Asthma
4 Severe Variable Allergic Asthma
5 Severe Fixed Airflow Asthma
1 MildAllergic Asthma
Moore et al. AJRCCM 2010;181:315-323.
Asthma Cluster Analysis: 5 Clusters
Multiscale Imaging-based Cluster Analysis (MICA) in Asthmatics
45
248 asthmatics
Choi, Chen, Hoffman, Wenzel, Castro, Fain, Jarjour, Schiebler, Lin, JACI 2017
Major Features of 4 Asthma Clusters
Development of COPD from Childhood Asthma – Results from the CAMP study
McGeachie MJ et al. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma N Engl J Med 2016;374:1842-1852
Development of COPD from Childhood Asthma – Results from the CAMP study
McGeachie MJ et al. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma N Engl J Med 2016;374:1842-1852
COPD, ACOS and chronic airflow obstruction phenotype
• Recognition of COPD in allergy or pulmonary practice requires spirometry
• Key to COPD assessment is symptom evaluation, exacerbation risk and spirometry
• Recognize the spectrum of Asthma COPD overlap and treat accordingly
• Chronic airflow obstruction phenotype can occur in asthma and is associated with difficult to control asthma
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