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    Allergy Phenotypes - Rhinitis

    Carmen Rondn, MD PhDAllergy Unit, Regional University Hospital

    Mlaga, Spain

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    Rhinitis a Complex SyndromeMultifactorial Etiology

    ENDOTYPES

    CLINICAL

    PRESENTATION

    EVOLUTION

    COMORBIDITIES

    TREATMENT

    PHENOTYPES

    GENOTYPE

    CLINICAL MANAGEMENT

    Rondon C. JIACI 2012

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    European Academy of Allergy and Clinical Immunology

    PRACTALL 2014: Phenotypes and Edotypes of Rhinitis

    TASK FORCE (ENT SECTION) 2014: Phenotype of NAR

    Under elaboration

    Under elaboration

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    ALLERGIC

    rhinitis

    INFECTIOUS

    rhinitisMIXED

    rhinitis

    Rhinitis Phenotypes Phenotypes can be dynamic and overlap or may

    develop into one another

    Different endotype may share a same phenotype

    Papadopoulos NG, et al. PRACTALL Phenotypes and Endotypes of rhinitis 2014 (under elaboration)Hellings PW, et al. Non-Allergic Rhintiis: Position paper of the EAACI (under elaboration)

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    ALLERGIC RHINITIS

    PHENOTYPES

    Rhinitis Phenotypes Phenotypes can be dynamic and overlap or may

    develop into one another

    Different endotype may share a same phenotype

    Papadopoulos NG, et al. PRACTALL Phenotypes and Endotypes of rhinitis 2014 (under elaboration)Hellings PW, et al. Non-Allergic Rhintiis: Position paper of the EAACI (under elaboration)

    Phenotypes

    Endotypes

    Differential diagnose

    Treatment

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    Rhinitis Phenotypes

    SEVERITY

    MILD

    MODERATE

    SEVERE

    SCUAD

    DURATION

    PERSISTENT

    INTERMITTENT

    ACUTE

    CHRONIC

    TEMPORAL

    SEASONAL

    PERENNIAL

    OCCUPATIONAL

    SYMPTOMS

    RUNNERS

    BLOCKERS

    CONTROL

    CONTROLLED

    UNCONTROLLED

    TREATMENT

    RESDONDERS

    NON RESPONDERS

    Papadopoulos NG, et al. PRACTALL Phenotypes and Endotypes of rhinitis 2014 (under elaboration)

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    Nasal Hyperreactivity

    Staevska M, N Baraniuk. C u r r A l l e r g y A s t h m a R ep 2005

    Salib RJ, et al. C l i n E x p A l l e r g y 2008

    Chemical irritants:

    Physical irritants:

    Tobacco smoke

    Pollutants: smog, diesel, SO2, NO2, CO, CO2

    Strong smells: perfumes, bleach, solvents

    Intense lightCold dry air: VR1 vanilloid receptor

    Hyperosmotic: pollen osmoreceptors

    Temperature and humidity changes

    ALLERGIC

    rhinitis

    INFECTIOU

    S rhinitisMIXED

    rhinitis

    NOT EXCLUSIVE ONLY IDIOPATHIC RHINITIS

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    Infectious rhinitis

    Etiology:

    Viral Rhinitis (Common cold): acute and self-limiting

    Bacterial Rhinosinusitis

    Fungal Rhinosinusitis

    Symptoms: Discolored rhinorrea

    Crust formation

    Duration of the disease: Acute (ARS)

    < 12 weeks and Complete resolution

    Chronic (CRS): 12 weeks and No complete resolution

    Papadopoulos NG, et al. PRACTALL Phenotypes and Endotypes of rhinitis 2014 (under elaboration)

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    Allergic rhinitis

    Global health problem

    Affecting 400 million persons Countries, ethnic groups, ages

    Impairment of quality of life

    Frequent co-morbidities

    Risk factor for development of asthma

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    ARIA Classification

    Bousquet J, et al. ARIA update 2008. Allergy 2008: 63 (Suppl. 86): 8160

    Time of exposure

    Seasonal

    Perennial

    Occupational AR

    Allergic rhinitis phenotypes

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    Nasal localizedallergic response

    Absence of

    Systemic Atopy

    Rondn C, et al.J Allergy Clin Immunol. 2012

    Clinical symptoms

    suggestive of AR

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    Th2 helper inflammatory patternPowe DG. Clin Exp Allery, 2001

    Powe DG. Allergy, 2004

    Rondn C. J Allergy Clin Immunol 2007

    Rondn C. Allergy 2008

    Nasal production of sIgEHuggins KG. J. Lancet, 1975

    Rondn C. J Allergy Clin Immunol, 2007

    Rondn C. Allergy, 2008

    Fuiano N, et al. Allergol Immunopathol 2012

    Reisacher WR, et al. Int Forum Allergy Rhinol 2014

    Positive response to NAPT

    Carney AS. Clin Exp Allergy, 2002Wedbck A. Rhinology, 2005

    Rondn C. J Allergy Clin Immunol, 2007

    Rondn C. Allergy 2008

    Rondn C. J Allergy Clin Immunol, 2009

    Lpez S. Clin Exp Allergy, 2010

    Rondn C, AAAAI 2011

    SymptomsRhinomanometry

    Acoustic Rhinometry

    Inflammatory Mediators and sIgE

    Cytokines (IFN-g, IL-1b, IL-2, IL-4, IL-6,IL-8, IL-12p70)

    Immunological characteristics

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    persistence

    91%

    9,1

    persistent

    intermittent

    severity

    5%

    36%

    59%

    mild

    moderate

    severe

    Local Allergic Rhinitis

    Rondn C, et al. Allergy 2012

    110 LAR patients

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    SAR(n=270) LAR(n=110) NAR(n=48)

    Age 18 ys 21 ys 36 ys (a,b)

    Woman 57.8% 78.2% 52.1% (a,b)

    Family history of atopy 37.4% 44.5% 20.8%

    Rhinitis

    Persistence

    Seasonality

    Severity

    persistent

    seasonal/perennial

    severe 59%

    persistent

    perennial

    severe 56%

    persistent

    perennial

    moderate 57%

    Nasal symptoms

    Frequently

    Severe

    itching, sneezing and

    watery rhinorrea

    watery rhinorrea

    itching, sneezing and

    watery rhinorrea

    watery rhinorrea

    obstruction and

    rmucous rhinorrea

    obstruction

    Triggering factors house dust

    pollen

    house dust

    pollen

    chemical irritants

    air conditioning

    Comorbidities

    Asthma

    Conjunctivitis

    Atopic dermatitis

    39%

    62%

    11%

    31%

    65%

    8%

    19%

    50%

    0%

    Onset childhood 38% 36% 9%

    (a,b)

    Rondn C, et al. Allergy 2012

    Demographic-clinical phenotype

    a: NAR vs SAR p

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    ARIA Treatment Strategy

    Bousquet J, et al. ARIA update 2008. Allergy 2008: 63 (Suppl. 86): 8160

    ALLERGIC RHINITIS

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    Allergen Immunotherapy

    Immune-modifying and etiologictreatment

    Safe and effective

    Symptom improvement and/or reduction

    of the use of rescues medication Long-lasting effect once discontinued

    Modify disease evolution

    Prevention of the onset of new skinsensitizations

    Prevention of the onset of asthma (?)

    Improvement of the quality of life

    Alvarez-Cuesta E. Clin Exp Allergy 2005Pfaar O. Allergy 2014

    Bousquet J. Allergy 1998Walker SM, JACI 2001

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    Allergen Immunotherapy

    Immune-modifying and etiologictreatment

    Safe and effective

    Symptom improvement and/or reduction

    of the use of rescues medication Long-lasting effect once discontinued

    Modify disease evolution

    Prevention of the onset of new skinsensitizations

    Prevention of the onset of asthma (?)

    Improvement of the quality of life

    Alvarez-Cuesta E. Clin Exp Allergy 2005Pfaar O. Allergy 2014

    Bousquet J. Allergy 1998Walker SM, JACI 2001

    Could LAR patients benefit from specific

    Immunotherapy? ?

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    Study Design: Pilot observational study in real condition

    Study Groups:20 adult LAR-grass:

    Immunotherapy: Aluminium-adsorbed grass mix pollen extract

    Study duration: One year : 6 months of preseasonal SCIT

    Rondn C, JACI 2011

    LAR: Allergen tolerance and immunologic

    changes after preseasonal SCIT- grass pollen

    SCIT group (N:10) = SCIT (6 months) + RM spring

    Control group (N:10) = RM spring

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    Rondn C et al., JACI 2011

    Immunotherapy in LAR6 month of preseasonal grass-SCIT

    Increase of tolerance 100%

    NAPT Neativization 30%

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    DBPC Clinical Trials (Phase 2 )

    1. Subcutaneous Immunotherapy with Dermatophagoides Pteronyssinus in

    local allergic rhinitis (ECRL1). EucraCT:2008-003680-39.

    NCT02123316.Completed 30-04-2014. Under analysis

    2. Efficacy of a Depigmented extract ofPhleum in local allergic rhinitis

    (GRAMAL). EudraCT:2010-020949-26. On going

    Efficacy of ITA in LAR

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    Subcutaneous Immunotherapy with

    Dermatophagoides Pteronyssinus in LAR

    (ECRL1 Study)

    ECRL1 sutdy. NCT02123316

    Study Type Interventional

    Study Design: Treatment, parallel assignment, randomized, double-

    blind, placebo-controled, safety/efficacy study

    Enrolment: 36 LAR patients

    Duration: 24 months

    Arms: Active = Pangramin Plus D. pteronyssinus 100%

    Placebo = Placebo

    Rescue medication

    (both arms):