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1. Dupilumab Efficacy in Patients with Uncontrolled Moderate-to-Severe Type 2 Asthma Regardless of Perennial Aeroallergen Sensitization

Author

Corren J, Jackson DJ, Casale TB, Borish L, Rabe KF, Busse WW, Maspero JF, Daizadeh N, Altincatal A, Radwan A, Khodzhayev A, Djandji M, Jacob-Nara JA, Rowe PJ, and Deniz Y

Subjects
dupilumab, allergic asthma, type 2 asthma, perennial aeroallergen, Immunologic diseases. Allergy, RC581-607
Abstract

Jonathan Corren,1 David J Jackson,2,3 Thomas B Casale,4 Larry Borish,5,6 Klaus F Rabe,7,8 William W Busse,9 Jorge F Maspero,10 Daniel J Jackson,11 Nadia Daizadeh,12 Arman Altincatal,12 Amr Radwan,13 Angela Khodzhayev,13 Michel Djandji,12 Juby A Jacob-Nara,12,14 Paul J Rowe,14 Yamo Deniz13 1David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2King’s College London, London, UK; 3Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 4Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA; 5Asthma and Allergic Disease Center, University of Virginia Health System, Charlottesville, VA, USA; 6Carter Immunology Center, University of Virginia Health System, Charlottesville, VA, USA; 7LungenClinic Grosshansdorf (Member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Grosshansdorf, Germany; 8Christian-Albrechts University (Member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Kiel, Germany; 9UW Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 10Fundación CIDEA, Buenos Aires, Argentina; 11University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 12Sanofi, Cambridge, MA, USA; 13Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 14Sanofi, Bridgewater, NJ, USACorrespondence: Jonathan Corren, David Geffen School of Medicine at UCLA, 10780 Santa Monica Blvd., Suite 280, Los Angeles, CA, 90025, USA, Email jcorren@ucla.eduPurpose: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 (T2) inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), dupilumab vs placebo significantly reduced asthma exacerbation rates (AER) and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma, with greater effects in patients with elevated T2 biomarkers (≥ 150 eosinophils/μL or fractional exhaled nitric oxide [FeNO] ≥ 25 parts per billion). Overall safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed dupilumab efficacy in QUEST patients with T2 asthma with evidence of an allergic phenotype (baseline serum IgE ≥ 30 IU/mL and aeroallergen-specific IgE ≥ 0.35 IU/mL) by number of aeroallergen sensitizations: 1, 2, 3, or ≥ 4. Non-sensitized patients (serum total IgE < 30 IU/mL without evidence of allergic phenotype) were also assessed.Patients and Methods: Endpoints were annualized AER, change from baseline in pre-bronchodilator FEV1 and asthma control (5-item Asthma Control Questionnaire [ACQ-5]), and FeNO and serum total IgE levels over the 52-week treatment period.Results: In all subgroups by number of allergens sensitized, dupilumab vs placebo reduced AER by 35– 67% and improved both pre-bronchodilator FEV1 at Week 12 (least squares mean differences: 0.10– 0.26 L across subgroups) and ACQ-5 score at Week 52 (– 0.26 to – 0.43). Dupilumab significantly reduced FeNO and total IgE levels at Week 52 compared with placebo. Similar results were observed in non-sensitized patients.Conclusion: Dupilumab improved clinical outcomes and reduced biomarker levels in patients with uncontrolled, moderate-to-severe T2 asthma irrespective of allergen sensitization status or number.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02414854.Keywords: dupilumab, allergic asthma, type 2 asthma, perennial aeroallergen

Published
2023

2. A Pragmatic Primary Practice Approach to Using Specific IgE in Allergy Testing in Asthma Diagnosis, Management, and Referral

Author

Demoly P, Liu AH, Rodriguez del Rio P, Pedersen S, Casale TB, and Price D

Subjects
primary care, allergy, asthma, sensitization, specific ige, component resolved diagnostics, Immunologic diseases. Allergy, RC581-607
Abstract

Pascal Demoly,1,2 Andrew H Liu,3 Pablo Rodriguez del Rio,4 Soren Pedersen,5 Thomas B Casale,6,7 David Price8 1Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, Montpellier, France; 2IDESP Inserm, University, Hospital of Montpellier, Montpellier, France; 3Airway Inflammation, Resilience & the Environment (AIRE) Program, Breathing Institute, Section of Pediatric Pulmonary & Sleep Medicine, Children’s Hospital Colorado, Professor of Pediatrics, University of Colorado School of Medicine, Adjunct Professor of Pediatrics, National Jewish Health, Denver, CO, USA; 4Pediatric Board of the EAACI, University Children’s Hospital, Madrid, Spain; 5GINA Program, Department of Pediatrics, Kolding Hospital, Kolding, Denmark; 6Food Allergy Research and Education (FARE), McLean, VA, USA; 7Department of Medicine and Pediatrics, University of South Florida, Tampa, FL, USA; 8Observational and Pragmatic Research Institute, SingaporeCorrespondence: David Price, Email dprice@opri.sgAbstract: Asthma afflicts an estimated 339 million people globally and is associated with ill health, disability, and early death. Strong risk factors for developing asthma are genetic predisposition and environmental exposure to inhaled substances that may provoke allergic reactions. Asthma guidelines recommend identifying causal or trigger allergens with specific IgE (sIgE) testing after a diagnosis of asthma has been made. Allergy testing with sIgE targets subpopulations of patients considered at high risk, such as those with frequent exacerbations, emergency visits or hospitalizations, or uncontrolled symptoms. Specific recommendations apply to preschool children, school-age children, patients with persistent or difficult-to-control asthma, patients needing oral corticosteroids or high-dose inhaled steroids, patients seeking understanding and guidance about their disease, and candidates for advanced therapies (biologics, allergen immunotherapy). Allergen skin testing is common in specialized settings but less available in primary care. Blood tests for total and sIgE are accessible and yield quantifiable results for tested allergens, useful for detecting sensitization. Results are interpreted in the context of the patient’s clinical presentation, age, and relevant allergen exposures. Incorporating sIgE testing into asthma management adds objective information to identify specific allergies and can guide personalized treatment plans, which reinforce patient-doctor communication. Test results can also be used to predict exacerbations and response to therapies. Additional diagnostic information can be gleaned from (i) eosinophil count ≥ 300 μL, which significantly increases the odds of having exacerbations, and emerging eosinophil biomarkers (eg, eosinophil-derived neurotoxin), which can be measured in plasma or serum samples, and (ii) fractional exhaled nitric oxide (FeNO), with values ≥ 25 ppb regarded as the cutoff for diagnosis, evaluating inhaled corticosteroid response, and of probable response to anti-IgE, anti-IL4 and anti-IL5 receptor biologics. Referral to asthma/allergy specialists is warranted when the initial diagnosis is uncertain, and when asthma symptoms, impairment, or exacerbations are repeated or severe.Keywords: primary care, allergy, asthma, sensitization, specific IgE, component resolved diagnostics

Published
2022

3. Role of biologics in intractable urticaria

Author

Cooke A, Bulkhi A, and Casale TB

Subjects
Medicine (General), R5-920
Abstract

Andrew Cooke,1 Adeeb Bulkhi,1,2 Thomas B Casale1 1Department of Internal Medicine, Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA; 2Department of Internal Medicine, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia Abstract: Chronic urticaria (CU) is a common condition faced by many clinicians. CU has been estimated to affect approximately 0.5%–1% of the population, with nearly 20% of sufferers remaining symptomatic 20 years after onset. Antihistamines are the first-line therapy for CU. Unfortunately, nearly half of these patients will fail this first-line therapy and require other medication, including immune response modifiers or biologics. Recent advances in our understanding of urticarial disorders have led to more targeted therapeutic options for CU and other urticarial diseases. The specific biologic agents most investigated for antihistamine-refractory CU are omalizumab, rituximab, and intravenous immunoglobulin (IVIG). Of these, the anti-IgE monoclonal antibody omalizumab is the best studied, and has recently been approved for the management of CU. Other agents, such as interleukin-1 inhibitors, have proved beneficial for Schnitzler syndrome and cryopyrin-associated periodic syndromes (CAPS), diseases associated with urticaria. This review summarizes the relevant data regarding the efficacy of biologics in antihistamine-refractory CU. Keywords: chronic urticaria, omalizumab, intravenous immunoglobulin, anakinra, canakinumab

Published
2015

8. Proceedings of the 2017 WAO Symposium on Hot Topics in Allergy: Pediatric & Regulatory Aspects: Rome, Italy/Vatican City. 27-29 April 2017

Author

Traina G, Valluzzi RL, Fierro V, Riccardi C, Artesani MC, De Vuono A, Fiocchi A, Martelli AG, Ríos LA, Alcocer CR, Navarrete E, Del Rio Navarro BE, Gonzalez V, Velasco B, Perez Aviles HJ, Fernandez RJ, Pozo FC, Farhan AJ, Arshad H, Hussain A, Sharikadze O, Okhotnikova O, Alcover J, Rodríguez Rius D, Pineda F, Dalal I, Weinbrand-Goichberg J, Benor S, Rottem M, Kivity S, Sato S, Yanagida N, Ebisawa M, Umanets T, Antipkin Y, Barzylovich V, Lapshyn V, Umanets M, Yuriev S, Rodriguez D, Bekir S, Pincock T, Vieira Hernandez A, Capriles Hulett A, Sánchez Borges M, Fabiano F, Albarran C, Goyal R, Gupta S, Gaurav G, Luskin AT, Griffin NM, Wagelie-Steffen A, Trzaskoma BL, Limb SL, Busse WW, Zeiger RS, Gonzalez-Reyes E, Casale TB, Chipps BE, Sugizaki C, Goto F, Yamaide A, Mitsunaga K, Tomiita M, Hoshioka A, Shimojo N, Pop LL, Ciuca IM, Tamas L, Lazarescu M, Pienar C, Yamaide F, Fikri B, Sato H, Okishima N, Kobayashi M, Takai M, Nishigata K, Yoda R, Oana YT, Kajiwara C, Shimodaira M, Suzuki T, Iizawa H, Kamijo K, Karmakar B, Bhattacharya SG, Blohlávková S, Kopelentová E, Víšek P, Štádler J, Šetinová I, Novobílská J, Lundelin K, Salminen S, Isolauri E, Pitt T, Flanders T, Peñalver M, Martínez P, Lluch-Canut T, Malet A, Nam YH, Jin HJ, Lee SK, Kulalert P, Sritipsukho P, Pathumanond J, Baynova K, Labella M, De Aramburu T, Prados M, Haanpää L, Aarnio J, Nermes M, Af Ursin P, Kaljonen A, Bala N, Bhagwat K, Hindley J, Chapman M, Baalasubramanian S, Besednjak-Kocijancic L, SenGupta K, Antonova E, Kong AM, Iqbal A, Teague WG, Ortiz B, Paknis B, Rosen K, Szefler S, Alblooshi A, Al-Hammadi S, Vega A, Gutiérrez-Rivas R, Alonso AM, Beitia JM, Belén Mateo M, Cárdenas R, García-Domínguez JJ, Pitchon Dos Reis R, Gonçalves Alvim C, Andrade C, Reis A, Ribeiro H, Panaitescu Bunu C, Marusciac L, Paralescu S, Tamas P, Martí Guadaño E, Escobar Bolaños C, Martí José N, Pau Casanovas P, Biarnés Rib G, Castells M, de Vicente Jiménez T, Mennini M, De Angelis P, Rea F, Malamisura M, Tambucci R, Dall'Oglio L, Del Chierico F, Napolitano T, Reddel S, Vernocchi P, D'Ambrosio A, Putignani L, Dahdah L, Banzato C, Plaza-Martín AM, Bosque García M, Íbero M, Mazzina O, Marzano V, Pecora V, Koch P, Valentini D, Santamaria F, Mukherjee A, Kandhare A, and Bodhankar S

Published
2017

10. International consensus on (ICON) pediatric asthma

Author

Papadopoulos NG, Arakawa H, Carlsen KH, Custovic A, Gern J, Lemanske R, Le Souef P, Makela M, Roberts G, Wong G, Zar H, Akdis CA, Bacharier LB, Baraldi E, van Bever HP, de Blic J, Boner A, Burks W, Casale TB, Castro-Rodriguez JA, Chen YZ, El-Gamal YM, Everard ML, Frischer T, and Geller M

Published
2012

11. Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome

Author

Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, Lemanske RF, Wardlaw AJ, Wenzel SE, and Greenberger PA

Subjects
respiratory tract diseases
Abstract

It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms which we have called "asthma endotypes.'' An "endotype'' is proposed to be a subtype of a condition defined by a distinct pathophysiological mechanism. Criteria for defining asthma endotypes on the basis of their phenotypes and putative pathophysiology are suggested. Using these criteria we identify several proposed asthma endotypes and propose how these new definitions can be used in clinical study design and drug development to target existing and novel therapies to patients most likely to benefit. This PRACTALL (PRACtical ALLergy) consensus report was produced by experts from the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy Asthma Immunology. (J Allergy Clin Immunol 2011;127:355 60.)

Published
2011

12. Severe Chronic Allergic (and Related) Diseases: A Uniform Approach - A MeDALL - GA(2)LEN - ARIA Position Paper

Author

WHO Collaborating Center for Asthma, Rhinitis, Bousquet J, Anto JM, Demoly P, Schünemann HJ, Togias A, Akdis M, Auffray C, Bachert C, Bieber T, Bousquet PJ, Carlsen KH, Casale TB, Cruz AA, Keil T, Lodrup Carlsen KC, Maurer M, Ohta K, Papadopoulos NG, Roman Rodriguez M, Samolinski B, Agache I, Andrianarisoa A, Ang CS, Annesi Maesano I, Ballester F, Baena Cagnani CE, Basagaña X, Bateman ED, Bel EH, Bedbrook A, Beghé B, Beji M, Ben Kheder A, Benet M, Bennoor KS, Bergmann KC, Berrissoul F, Bindslev Jensen C, Bleecker ER, BONINI, Sergio, WHO Collaborating Center for, Asthma, Rhinitis, Bousquet, J, Anto, Jm, Demoly, P, Schünemann, Hj, Togias, A, Akdis, M, Auffray, C, Bachert, C, Bieber, T, Bousquet, Pj, Carlsen, Kh, Casale, Tb, Cruz, Aa, Keil, T, Lodrup Carlsen, Kc, Maurer, M, Ohta, K, Papadopoulos, Ng, Roman Rodriguez, M, Samolinski, B, Agache, I, Andrianarisoa, A, Ang, C, Annesi Maesano, I, Ballester, F, Baena Cagnani, Ce, Basagaña, X, Bateman, Ed, Bel, Eh, Bedbrook, A, Beghé, B, Beji, M, Ben Kheder, A, Benet, M, Bennoor, K, Bergmann, Kc, Berrissoul, F, Bindslev Jensen, C, Bleecker, Er, and Bonini, Sergio

Published
2013

13. Practical guide to skin prick tests in allergy to aeroallergens

Author

Bousquet, J, Heinzerling, L, Bachert, C, Papadopoulos, NG, Bousquet, PJ, Burney, PG, Canonica, GW, Carlsen, KH, Cox, L, Haahtela, T, Carlsen, KCL, Price, D, Samolinski, B, Simons, FER, Wickman, M, Annesi-Maesano, I, Baena-Cagnani, CE, Bergmann, KC, Bindslev-Jensen, C, Casale, TB, Chiriac, A, Cruz, AA, Dubakiene, R, Durham, SR, Fokkens, WJ, Gerth van Wijk, Roy, Kalayci, O, Kowalski, ML, Mari, A, Mullol, J, Nazamova-Baranova, L, O'Hehir, RE, Ohta, K, Panzner, P, Passalacqua, G, Ring, J, Rogala, B, Romano, A, Ryan, D, Schmid-Grendelmeier, P, Todo-Bom, A, Valenta, R, Woehrl, S, Yusuf, OM, Zuberbier, T, Demoly, P, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Bousquet J, Heinzerling L, Bindslev-Jensen C, Casale TB, Bachert C, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth-van-Wijk R, Kalayci O, Lodrup Carlsen KC, Kowalski ML, Mari A, Mullol J, Papadopoulos NG, Nazamova-Baranova L, O'Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Price D, Rogala B, Romano A, Ryan D, Schmid-Grendelmeier P, Bousquet PJ, Todo-Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Samolinski B, Demoly P, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Simons FE, Wickman M, Annesi-Maesano I, Baena-Cagnani CE, Bergmann KC, AII - Amsterdam institute for Infection and Immunity, Ear, Nose and Throat, University of Zurich, Bousquet, J, Dermatology, and Internal Medicine

Subjects
2403 Immunology, Air Pollutants, 2723 Immunology and Allergy, Hypersensitivity, 10177 Dermatology Clinic, Humans, 610 Medicine & health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Allergens, Skin Tests
Abstract

International audience; To cite this article: Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC, Price D, Samolinski B, Simons FER, Wickman M, Annesi-Maesano I, Baena-Cagnani CE, Bergmann KC, Bindslev-Jensen C, Casale TB, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth-van-Wijk R, Kalayci O, Kowalski ML, Mari A, Mullol J, Nazamova-Baranova L, O'Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Rogala B, Romano A, Ryan D, Schmid-Grendelmeier P, Todo-Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Demoly P. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02728.x ABSTRACT: This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

Published
2011

14. Reply

Author

Brożek JL, Bousquet J, Baena Cagnani CE, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, Schünemann H.J., BONINI, Sergio, Brożek, Jl, Bousquet, J, Baena Cagnani, Ce, Bonini, Sergio, Canonica, Gw, Casale, Tb, van Wijk, Rg, Ohta, K, Zuberbier, T, and Schünemann, H. J.

Published
2011

15. Global Allergy and Asthma European Network: Grading of Recommendations Assessment, Development and Evaluation Working Group: Allewrgic Rhinitis and its Impact on Asthma (ARIA) Guidelines: 2010 revision

Author

Brozek JL, Bousquet J, Baena Cagnani CE, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, Schunemann H.J., BONINI, Sergio, Brozek, Jl, Bousquet, J, Baena Cagnani, Ce, Bonini, Sergio, Canonica, Gw, Casale, Tb, van Wijk, Rg, Ohta, K, Zuberbier, T, and Schunemann, H. J.

Published
2010

16. Unmet needs in severe chronic upper airway disease (SCUAD)

Author

BOUSQUET J, BACHERT C, CANONICA GW, CASALE TB, CRUZ AA, LOCKEY RJ, ZUBERBIER T, WORLD ALLERGY ORGANIZATION AND ALLERGIC RHINITIS AND ITS IMPACT ON ASTHMA STUDY GROUP, BONINI, Sergio, Bousquet, J, Bachert, C, Canonica, Gw, Casale, Tb, Cruz, Aa, Lockey, Rj, Zuberbier, T, Bonini, Sergio, and WORLD ALLERGY ORGANIZATION AND ALLERGIC RHINITIS AND ITS IMPACT ON ASTHMA STUDY, Group

Published
2009

17. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma

Author

BUSSE WW, PEDERSEN S, PAUWELS RA, TAN WC, CHEN YZ, LAMM CJ, Eckmayr J, Riedler J, Wurzinger G, Ott G, Zarkovic J, Schulheim A, Götz M, Schinko H, Thomüller I, de Backer W, van Bever H, Verleden G, de Boeck C, Aumann J, Vincken W, Dab I, de Vuyst P, de Jonghe M, Casimir G, Joos G, de Baets F, Bogaerts Y, Halloy JL, Bartsch P, Thiriaux J, Pohunek P, Rybníćek O, Skopková O, Pavelková L, Broź P, Ohnutková E, Novotná B, Baly J, Krćmová I, Kuralová Z, Koćí T, Honomichlová H, Kaśák V, Panzner P, Vondra V, Némećková J, Seberová E, Sykora T, Vít P, Turzíková J, Sörensen T, Neldam S, Peter J, Kludt J, Hansen UB, Knudsen T, Schultz PJ, Rost D, Jensen F, Kinnula V, Saarelainen P, Eho Remes M, Valovirta E, Venho KK, Kokko E, Järvinen M, Toljamo T, Taivainen A, Kava T, Herrala J, Kuusela AL, Nordgren P, Syvänen P, Godard P, Rufin P, Anton M, Aubert JP, Grosclaude M, Brambilla C, Archaud P, Racineux JL, Muir JF, Albertini M, Le Roux P, Simmons A, Bartuschka B, von Berg A, Bergmann V, Berns J, Bisping Arnold A, Blum HC, Garanin G, Brückner OJ, Burbach P, Sudhoff H, Feldmann M, Schmoller T, Wozny HW, Galaske R, Huptas M, Kaecke J, Köcher V, Laule Peschel M, Lohr E, Goldberg J, Drescher T, Reeh W, Rabe U, Rehn L, Scheffler NK, Steinmetz KO, Stutz PM, Weber HH, Uhde C, Ullner R, Vehar H, Krohn EU, Orosz M, Devai A, Uhereczky G, Rajkay K, Gönczi F, Györi E, Dobra G, Puha K, Sztancsik Z, Gömöri K, Dolinay T, Bittera I, Palinkasi S, Cseke Z, Bisits M, Bjämer D, Holme JI, Langhammer A, Hunstad K, Holmboe JH, Grangård E, Solberg DA, Grönneröd TA, Salkowitsch MB, Oymar K, Iversen K, Szczeklik A, Chyrek Borowska S, Mincewicz G, Malaczynska T, Latos T, Obtulowicz K, Emeryk A, Gorski P, Nowak D, Szmidt M, Alkiewicz J, Ziolo G, Spychalski L, Chmielewska Szewczyk D, Nowacka K, Pirozynski M, Prokurat H, Boznanski A, Malolepszy J, Rogala E, Kozielski J, Eriksson UL, Wahlestedt H, Selberg M, Larsson R, Rignér K, Alm B, Aronsson M, Winnergård I, Lagerwall M, Martinsons U, Berlin L, Rydberg B, Weston D, Johnson ME, Barrett C, Siafakas N, Mantzourani E, Orphanidou D, Trakopoulos G, Tzannes S, Kotsovoulou V, Dimadi M, Amfilochiou A, Priftis K, Papageorgiou Saxoni F, Christaki P, Tsanakas I, Paraskevi M, Bousmoukilia S, Spiropoulos K, Anthrakopoulos M, Roussos C, Bentur Alkouby L, Heimer D, Tal A, Horowitz I, Soferman R, Katz Y, Stav D, Weiler Z, Bibi H, Rottem M, Mandelberg A, Geller C, Roizin H, Weiler Ravell D, Kramer MR, Schwartz Y, Rossi A, Foresi A, Giuntini C, Bisetti A, Scoditti S, Tranfa C, Zacchello F, Giovannini M, Boner A, Fabbri LM, Girbino G, Barberio G, Cacciari E, Montefort S, Parascandalo R, Pato R, de Lourdes Chieira M, Moreira C, Chieira DS, Brito U, Borges FD, Marques AC, Figueiredo MM, Dias F, de Almeida AB, Cesar Ramos J, Valente MJ, Pereira JD, Nunes C, Riberio MF, Marques A, Carvalho MQ, de Azevedo MV, de Almeida AR, Pinto JA, Matos Mde F, Afonso A, Dos Santos JM, Fernandez CV, Agustin IC, Bejarano JM, Santos AA, Font ET, Huet EH, Lorente TL, Pujol MM, Munoz AP, Aineto PS, Forns SB, Areu JB, Casan P, Garcia JM, Rodriguez AV, Segura PA, Gil RS, Ciscar CP, Garcia JF, Jimenez TV, Gonzalez JI, Andres FQ, Bueno TA, Baticon CO, Miguel CR, Garcia FD, Hernando HV, Vina AL, Matia RA, Cumplido AS, Andueza MC, Cabra MS, Navarro PL, Rodriguez FA, Li JH, Landry D, O'Keefe D, Muram BF, Conter HS, Tweel D, Peters SD, Adelglass J, Baker JW, Berger WE, Bernstein DI, Blake KV, Amelong P, Casale TB, Charous BL, Chervinsky P, Condemi JJ, Cook D, Creticos PS, de Graff AC Jr, Smith T, Ellis MH, Grossman J, Halverson PC, Galant S, Hollingsworth H, Jackson C, Jacobs RL, Welch M, Kraemer MJ, Leflein J, Lemanske RF, Liebhaber MI, Lockey R, Kelly B, Mendelson L, Nayak A, Pearlman DS, Ruff M, Schwartz B, Scott MB, Shapiro GG, Silk HJ, Skoner DP, Stoloff S, Swamy KN, Atkins FM, Szefler SJ, Vandewalker M, Wald J, Weinstein SF, Wong DA, Wu F, Goldstein S, Murthy KC, Dolmann A, Gene R, Casas JC, Piovano C, Segal E, Balanzat AM, Taborda J, Truganti A, Teper A, Garrood J, Patel MJ, Hogan C, Russel G, Zhu YJ, Cao L, Liu SY, Miao JZ, Ding DJ, Yao WZ, Liu YN, Chen P, Kong SQ, Pang L, Sun B, Li ZM, Li GS, Chen PL, Zhu Q, Zhang TX, Wang XH, Wei S, Deng WW, Zhou X, Ji YY, Luo WT, Li Q, Zhu HR, Sheng JY, Ma JY, Zhang DP, Ji CZ, Xia XR, Zhang ZY, Yin KS, Yiang J, Li Y, Tang PW, Liu FG, Wang HP, Zhong NS, Rong ZS, Tang YC, Lin CY, Liu JS, Liu HZ, Cai DM, Yang JC, Ma QF, Mangunnegoro H, Wijono CA, Tobing NH, Rahajoe NN, Sugito, Surjanto E, Hisyam B, Alsagaff H, Santosa G, Kim YY, Park CS, Kim MK, Cho YJ, Choi DC, Jee YK, Mohan J, Yogeswery S, Wong SL, Kuan GL, Koh CT, Quah BS, de Bruyne J, Liam CK, Avila MM, Cuevas F, Chavaje N, Topete LA, Badillo I, Ponce M, Merida JC, Espinosa AG, Ledezma JM, García JA, Morales GG, Gomez JM, Martinez FJ, Ramos JE, Dorantes JR, Gonzalez CC, Vera JG, Bayardo RG, Melendez AP, Loyola CB, Suárez MA, de Guia T, Balgos A, Bautista N, Realiza T, Diaz D, Yu C, Mendoza Wi JA, Juaneza R, Bigornia R, Mansukhani P, Cacanindin DN, Wah LB, Hon YK, Yau OY, Moh CO, Tang WY, Dippenaar YD, Kirsten DL, Maraschin EF, Ossip MS, Visser SS, Mouton WL, Mercer M, Cassim KM, Macleod AH, Bateman ED, Leaver R, Morison A, Nel H, von Delft KH, Vermeulen JH, Weinberg EG, Lund RJ, Weber HC, Kuo SH, Kuo HP, Wang JL, Hsiue TR, Wang JH, Ching CD, Vangveeravong M, Pothiratana C, Trakultivakorn M, Kongpanichkul A, Thamanavat B, Fuangtong R, Suntornlohanakul S, Youngchaiyud P, Teeratakulpisarn J, Boonsawat W, Viriyachaiyo V, Direkwattanachai C, Visitsunthorn N., MIRAGLIA DEL GIUDICE, Michele, Busse, Ww, Pedersen, S, Pauwels, Ra, Tan, Wc, Chen, Yz, Lamm, Cj, Eckmayr, J, Riedler, J, Wurzinger, G, Ott, G, Zarkovic, J, Schulheim, A, Götz, M, Schinko, H, Thomüller, I, de Backer, W, van Bever, H, Verleden, G, de Boeck, C, Aumann, J, Vincken, W, Dab, I, de Vuyst, P, de Jonghe, M, Casimir, G, Joos, G, de Baets, F, Bogaerts, Y, Halloy, Jl, Bartsch, P, Thiriaux, J, Pohunek, P, Rybníćek, O, Skopková, O, Pavelková, L, Broź, P, Ohnutková, E, Novotná, B, Baly, J, Krćmová, I, Kuralová, Z, Koćí, T, Honomichlová, H, Kaśák, V, Panzner, P, Vondra, V, Némećková, J, Seberová, E, Sykora, T, Vít, P, Turzíková, J, Sörensen, T, Neldam, S, Peter, J, Kludt, J, Hansen, Ub, Knudsen, T, Schultz, Pj, Rost, D, Jensen, F, Kinnula, V, Saarelainen, P, Eho Remes, M, Valovirta, E, Venho, Kk, Kokko, E, Järvinen, M, Toljamo, T, Taivainen, A, Kava, T, Herrala, J, Kuusela, Al, Nordgren, P, Syvänen, P, Godard, P, Rufin, P, Anton, M, Aubert, Jp, Grosclaude, M, Brambilla, C, Archaud, P, Racineux, Jl, Muir, Jf, Albertini, M, Le Roux, P, Simmons, A, Bartuschka, B, von Berg, A, Bergmann, V, Berns, J, Bisping Arnold, A, Blum, Hc, Garanin, G, Brückner, Oj, Burbach, P, Sudhoff, H, Feldmann, M, Schmoller, T, Wozny, Hw, Galaske, R, Huptas, M, Kaecke, J, Köcher, V, Laule Peschel, M, Lohr, E, Goldberg, J, Drescher, T, Reeh, W, Rabe, U, Rehn, L, Scheffler, Nk, Steinmetz, Ko, Stutz, Pm, Weber, Hh, Uhde, C, Ullner, R, Vehar, H, Krohn, Eu, Orosz, M, Devai, A, Uhereczky, G, Rajkay, K, Gönczi, F, Györi, E, Dobra, G, Puha, K, Sztancsik, Z, Gömöri, K, Dolinay, T, Bittera, I, Palinkasi, S, Cseke, Z, Bisits, M, Bjämer, D, Holme, Ji, Langhammer, A, Hunstad, K, Holmboe, Jh, Grangård, E, Solberg, Da, Grönneröd, Ta, Salkowitsch, Mb, Oymar, K, Iversen, K, Szczeklik, A, Chyrek Borowska, S, Mincewicz, G, Malaczynska, T, Latos, T, Obtulowicz, K, Emeryk, A, Gorski, P, Nowak, D, Szmidt, M, Alkiewicz, J, Ziolo, G, Spychalski, L, Chmielewska Szewczyk, D, Nowacka, K, Pirozynski, M, Prokurat, H, Boznanski, A, Malolepszy, J, Rogala, E, Kozielski, J, Eriksson, Ul, Wahlestedt, H, Selberg, M, Larsson, R, Rignér, K, Alm, B, Aronsson, M, Winnergård, I, Lagerwall, M, Martinsons, U, Berlin, L, Rydberg, B, Weston, D, Johnson, Me, Barrett, C, Siafakas, N, Mantzourani, E, Orphanidou, D, Trakopoulos, G, Tzannes, S, Kotsovoulou, V, Dimadi, M, Amfilochiou, A, Priftis, K, Papageorgiou Saxoni, F, Christaki, P, Tsanakas, I, Paraskevi, M, Bousmoukilia, S, Spiropoulos, K, Anthrakopoulos, M, Roussos, C, Bentur Alkouby, L, Heimer, D, Tal, A, Horowitz, I, Soferman, R, Katz, Y, Stav, D, Weiler, Z, Bibi, H, Rottem, M, Mandelberg, A, Geller, C, Roizin, H, Weiler Ravell, D, Kramer, Mr, Schwartz, Y, Rossi, A, Foresi, A, Giuntini, C, Bisetti, A, Scoditti, S, Tranfa, C, Zacchello, F, Giovannini, M, Boner, A, MIRAGLIA DEL GIUDICE, Michele, Fabbri, Lm, Girbino, G, Barberio, G, Cacciari, E, Montefort, S, Parascandalo, R, Pato, R, de Lourdes Chieira, M, Moreira, C, Chieira, D, Brito, U, Borges, Fd, Marques, Ac, Figueiredo, Mm, Dias, F, de Almeida, Ab, Cesar Ramos, J, Valente, Mj, Pereira, Jd, Nunes, C, Riberio, Mf, Marques, A, Carvalho, Mq, de Azevedo, Mv, de Almeida, Ar, Pinto, Ja, Matos Mde, F, Afonso, A, Dos Santos, Jm, Fernandez, Cv, Agustin, Ic, Bejarano, Jm, Santos, Aa, Font, Et, Huet, Eh, Lorente, Tl, Pujol, Mm, Munoz, Ap, Aineto, P, Forns, Sb, Areu, Jb, Casan, P, Garcia, Jm, Rodriguez, Av, Segura, Pa, Gil, R, Ciscar, Cp, Garcia, Jf, Jimenez, Tv, Gonzalez, Ji, Andres, Fq, Bueno, Ta, Baticon, Co, Miguel, Cr, Garcia, Fd, Hernando, Hv, Vina, Al, Matia, Ra, Cumplido, A, Andueza, Mc, Cabra, M, Navarro, Pl, Rodriguez, Fa, Li, Jh, Landry, D, O'Keefe, D, Muram, Bf, Conter, H, Tweel, D, Peters, Sd, Adelglass, J, Baker, Jw, Berger, We, Bernstein, Di, Blake, Kv, Amelong, P, Casale, Tb, Charous, Bl, Chervinsky, P, Condemi, Jj, Cook, D, Creticos, P, de Graff AC, Jr, Smith, T, Ellis, Mh, Grossman, J, Halverson, Pc, Galant, S, Hollingsworth, H, Jackson, C, Jacobs, Rl, Welch, M, Kraemer, Mj, Leflein, J, Lemanske, Rf, Liebhaber, Mi, Lockey, R, Kelly, B, Mendelson, L, Nayak, A, Pearlman, D, Ruff, M, Schwartz, B, Scott, Mb, Shapiro, Gg, Silk, Hj, Skoner, Dp, Stoloff, S, Swamy, Kn, Atkins, Fm, Szefler, Sj, Vandewalker, M, Wald, J, Weinstein, Sf, Wong, Da, Wu, F, Goldstein, S, Murthy, Kc, Dolmann, A, Gene, R, Casas, Jc, Piovano, C, Segal, E, Balanzat, Am, Taborda, J, Truganti, A, Teper, A, Garrood, J, Patel, Mj, Hogan, C, Russel, G, Zhu, Yj, Cao, L, Liu, Sy, Miao, Jz, Ding, Dj, Yao, Wz, Liu, Yn, Chen, P, Kong, Sq, Pang, L, Sun, B, Li, Zm, Li, G, Chen, Pl, Zhu, Q, Zhang, Tx, Wang, Xh, Wei, S, Deng, Ww, Zhou, X, Ji, Yy, Luo, Wt, Li, Q, Zhu, Hr, Sheng, Jy, Ma, Jy, Zhang, Dp, Ji, Cz, Xia, Xr, Zhang, Zy, Yin, K, Yiang, J, Li, Y, Tang, Pw, Liu, Fg, Wang, Hp, Zhong, N, Rong, Z, Tang, Yc, Lin, Cy, Liu, J, Liu, Hz, Cai, Dm, Yang, Jc, Ma, Qf, Mangunnegoro, H, Wijono, Ca, Tobing, Nh, Rahajoe, Nn, Sugito, Surjanto, E, Hisyam, B, Alsagaff, H, Santosa, G, Kim, Yy, Park, C, Kim, Mk, Cho, Yj, Choi, Dc, Jee, Yk, Mohan, J, Yogeswery, S, Wong, Sl, Kuan, Gl, Koh, Ct, Quah, B, de Bruyne, J, Liam, Ck, Avila, Mm, Cuevas, F, Chavaje, N, Topete, La, Badillo, I, Ponce, M, Merida, Jc, Espinosa, Ag, Ledezma, Jm, García, Ja, Morales, Gg, Gomez, Jm, Martinez, Fj, Ramos, Je, Dorantes, Jr, Gonzalez, Cc, Vera, Jg, Bayardo, Rg, Melendez, Ap, Loyola, Cb, Suárez, Ma, de Guia, T, Balgos, A, Bautista, N, Realiza, T, Diaz, D, Yu, C, Mendoza Wi, Ja, Juaneza, R, Bigornia, R, Mansukhani, P, Cacanindin, Dn, Wah, Lb, Hon, Yk, Yau, Oy, Moh, Co, Tang, Wy, Dippenaar, Yd, Kirsten, Dl, Maraschin, Ef, Ossip, M, Visser, S, Mouton, Wl, Mercer, M, Cassim, Km, Macleod, Ah, Bateman, Ed, Leaver, R, Morison, A, Nel, H, von Delft, Kh, Vermeulen, Jh, Weinberg, Eg, Lund, Rj, Weber, Hc, Kuo, Sh, Kuo, Hp, Wang, Jl, Hsiue, Tr, Wang, Jh, Ching, Cd, Vangveeravong, M, Pothiratana, C, Trakultivakorn, M, Kongpanichkul, A, Thamanavat, B, Fuangtong, R, Suntornlohanakul, S, Youngchaiyud, P, Teeratakulpisarn, J, Boonsawat, W, Viriyachaiyo, V, Direkwattanachai, C, and Visitsunthorn, N.

Published
2008

18. Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs

Author

Bousquet J, Schünemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, Bonini S, Boulet LP, Bousquet PJ, Brozek JL, Canonica GW, Casale TB, Cruz AA, Fokkens WJ, Fonseca JA, van Wijk RG, Grouse L, Haahtela T, Khaltaev N, Kuna P, Lockey RF, Lodrup Carlsen KC, Mullol J, Naclerio R, O'Hehir RE, Ohta K, Palkonen S, Papadopoulos NG, Passalacqua G, Pawankar R, Price D, Ryan D, Simons FE, Togias A, Williams D, Yorgancioglu A, Yusuf OM, Aberer W, Adachi M, Agache I, Aït-Khaled N, Akdis CA, Andrianarisoa A, Annesi-Maesano I, Ansotegui IJ, Baiardini I, Bateman ED, Bedbrook A, Beghé B, Beji M, Bel EH, Ben Kheder A, Bennoor KS, Bergmann KC, Berrissoul F, Bieber T, Bindslev Jensen C, Blaiss MS, Boner AL, Bouchard J, Braido F, Brightling CE, Bush A, Caballero F, Calderon MA, Calvo MA, Camargos PA, Caraballo LR, Carlsen KH, Carr W, Cepeda AM, Cesario A, Chavannes NH, Chen YZ, Chiriac AM, Chivato Pérez T, Chkhartishvili E, Ciprandi G, Costa DJ, Cox L, Custovic A, Dahl R, Darsow U, De Blay F, Deleanu D, Denburg JA, Devillier P, Didi T, Dokic D, Dolen WK, Douagui H, Dubakiene R, Durham SR, Dykewicz MS, El-Gamal Y, El-Meziane A, Emuzyte R, Fiocchi A, Fletcher M, Fukuda T, Gamkrelidze A, Gereda JE, González Diaz S, Gotua M, Guzmán MA, Hellings PW, Hellquist-Dahl B, Horak F, Hourihane JO, Howarth P, Humbert M, Ivancevich JC, Jackson C, Just J, Kalayci O, Kaliner MA, Kalyoncu AF, Keil T, Keith PK, Khayat G, Kim YY, Koffi N'goran B, Koppelman GH, Kowalski ML, Kull I, Kvedariene V, Larenas-Linnemann D, Le LT, Lemière C, Li J, Lieberman P, Lipworth B, Mahboub B, Makela MJ, Martin F, Marshall GD, Martinez FD, Masjedi MR, Maurer M, Mavale-Manuel S, Mazon A, Melen E, Meltzer EO, Mendez NH, Merk H, Mihaltan F, Mohammad Y, Morais-Almeida M, Muraro A, Nafti S, Namazova-Baranova L, Nekam K, Neou A, Niggemann B, Nizankowska-Mogilnicka E, Nyembue TD, Okamoto Y, Okubo K, Orru MP, Ouedraogo S, Ozdemir C, Panzner P, Pali-Schöll I, Park HS, Pigearias B, Pohl W, Popov TA, Postma DS, Potter P, Rabe KF, Ratomaharo J, Reitamo S, Ring J, Roberts R, Rogala B, Romano A, Roman Rodriguez M, Rosado-Pinto J, Rosenwasser L, Rottem M, Sanchez-Borges M, Scadding GK, Schmid-Grendelmeier P, Sheikh A, Sisul JC, Solé D, Sooronbaev T, Spicak V, Spranger O, Stein RT, Stoloff SW, Sunyer J, Szczeklik A, Todo-Bom A, Toskala E, Tremblay Y, Valenta R, Valero AL, Valeyre D, Valiulis A, Valovirta E, Van Cauwenberge P, Vandenplas O, van Weel C, Vichyanond P, Viegi G, Wang DY, Wickman M, Wöhrl S, Wright J, Yawn BP, Yiallouros PK, Zar HJ, Zernotti ME, Zhong N, Zidarn M, Zuberbier T, World Health Organization Collaborating Center for Asthma, and Rhinitis.

Published
2012

19. Severe Chronic Allergic (and related) Diseases: a uniform approach- a MeDALL- GA(2)LEN-ARIA Position Paper

Author

WHO Collaborating Center for Asthma, Rhinitis, Bousquet, J, Anto, Jm, Demoly, P, Schünemann, Hj, Togias, A, Akdis, M, Auffray, C, Bachert, C, Bieber, T, Bousquet, Pj, Carlsen, Kh, Casale, Tb, Cruz, Aa, Keil, T, Lodrup Carlsen KC, Maurer, M, Ohta, K, Papadopoulos, Ng, Roman Rodriguez, M, Samolinski, B, Agache, I, Andrianarisoa, A, Ang, Cs, Annesi Maesano, I, Ballester, F, Baena Cagnani CE, Basagaña, X, Bateman, Ed, Bel, Eh, Bedbrook, A, Beghe', Bianca, Beji, M, Ben Kheder, A, Benet, M, Bennoor, Ks, Bergmann, Kc, Berrissoul, F, Bindslev Jensen, C, Bleecker, Er, Bonini, S, Boner, Al, Boulet, Lp, Brightling, Ce, Brozek, Jl, Bush, A, Busse, Ww, Camargos, Pa, Canonica, Gw, Carr, W, Cesario, A, Chen, Yz, Chiriac, Am, Costa, Dj, Cox, L, Custovic, A, Dahl, R, Darsow, U, Didi, T, Dolen, Wk, Douagui, H, Dubakiene, R, El Meziane, A, Fonseca, Ja, Fokkens, Wj, Fthenou, E, Gamkrelidze, A, Garcia Aymerich, J, Gerth van Wijk, R, Gimeno Santos, E, Guerra, S, Haahtela, T, Haddad, H, Hellings, Pw, Hellquist Dahl, B, Hohmann, C, Howarth, P, Hourihane, Jo, Humbert, M, Jacquemin, B, Just, J, Kalayci, O, Kaliner, Ma, Kauffmann, F, Kerkhof, M, Khayat, G, Koffi N'Goran, B, Kogevinas, M, Koppelman, Gh, Kowalski, Ml, Kull, I, Kuna, P, Larenas, D, Lavi, I, Le, Lt, Lieberman, P, Lipworth, B, Mahboub, B, Makela, Mj, Martin, F, Martinez, Fd, Marshall, Gd, Mazon, A, Melen, E, Meltzer, Eo, Mihaltan, F, Mohammad, Y, Mohammadi, A, Momas, I, Morais Almeida, M, Mullol, J, Muraro, A, Naclerio, R, Nafti, S, Namazova Baranova, L, Nawijn, Mc, Nyembue, Td, Oddie, S, O'Hehir, Re, Okamoto, Y, Orru, Mp, Ozdemir, C, Ouedraogo, Gs, Palkonen, S, Panzner, P, Passalacqua, G, Pawankar, R, Pigearias, B, Pin, I, Pinart, M, Pison, C, Popov, Ta, Porta, D, Postma, Ds, Price, D, Rabe, Kf, Ratomaharo, J, Reitamo, S, Rezagui, D, Ring, J, Roberts, R, Roca, J, Rogala, B, Romano, A, Rosado Pinto, J, Ryan, D, Sanchez Borges, M, Scadding, Gk, Sheikh, A, Simons, Fe, Siroux, V, Schmid Grendelmeier PD, Smit, Ha, Sooronbaev, T, Stein, Rt, Sterk, Pj, Sunyer, J, Terreehorst, I, Toskala, E, Tremblay, Y, Valenta, R, Valeyre, D, Vandenplas, O, van Weel, C, Vassilaki, M, Varraso, R, Viegi, G, Wang, Dy, Wickman, M, Williams, D, Wöhrl, S, Wright, J, Yorgancioglu, A, Yusuf, Om, Zar, Hj, Zernotti, Me, Zidarn, M, Zhong, N, Zuberbier, T., Beghe', B., Fthenou, E., Boudier, Anne, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), IMIM-Hospital del Mar, Generalitat de Catalunya, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER Epidemiologia y Salud Publica, CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), WHO Collaborating Center for Asthma and Rhinitis, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Génomique fonctionnelle et biologie systémique pour la santé, Institut des Sciences Biologiques du CNRS, Upper Airway Research Laboratory (URL), Ghent University Hospital, Department of Dermatology and Allergy, VU University Medical Center [Amsterdam], Department of Paediatrics, University of Oslo (UiO)-Oslo University Hospital [Oslo], Division of Allergy and Immunology, Department of Medicine, Creighton University, ProAR - FMB, Federal University of Bahia School of Medicine, Epidemiology and Health Economics, Instittute of Social Health-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Division of Respiratory Medicine and Allergology, Teikyo University School of Medicine, Allergy Department, 2nd Pediatric Clinic, Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Public Hospital Medical Service, Ministry of Health [Mozambique], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Public Health Research (CSISP), University of Valencia, Respiratory Medicine, Università degli studi di Genova = University of Genoa (UniGe)-School of Specialization, Faculty of Medicine, Catholic University, Health Sciences Faculty, University of Cape Town, Department of Pulmonology, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Centre, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Service de Pneumologie Allergologie, Hôpital La Rabta [Tunis], Service de Pneumologie, Hôpital Abderrahmen Mami, National Asthma Centre, National Institute of Diseases of the Chest and Hospital (NIDCH), Pneumologie / Anesthésie - réanimation / Oxygénothérapie, Hôpital AKS Phnom Penh-Hôpital Provincial de Siemreap, Department of Dermatology and Allergy Center, Odense University Hospital, Center for Genomics and Personalized Medicine, Wake Forest University, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Verona = University of Verona (UNIVR), Institut de cardiologie et de pneumologie, Université Laval [Québec] (ULaval)-Centre Hospitalier de Laval (CH Laval), Department of Respiratory Medicine and Thoracic Surgery, University of Leicester-Institute for Lung Health, Department of Paediatric Respiratory Medicine, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], Department of Medicine, University of Wisconsin School of Medicine and Public Health, Department of Pediatrics, Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG)-Medical School, Allergy & Respiratory Diseases, Università degli studi di Genova = University of Genoa (UniGe)-Department of Internal Medicine (DIMI), Allergy & Asthma Associates, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Deputy Scientific Director, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Department of Thoracic Surgery, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), National Cooperative Group of Pediatric Research on Asthma, Asthma Clinic and Education Center of the Capital Institute of Pediatrics, Service des Premiers Soins, Université Montpellier 1 (UM1), Osteopathic College of Medicine, Nova Southeastern University (NSU), Respiratory Research Group, University of Manchester [Manchester]-School of Translational Medicine, Department of Respiratory Diseases, Aarhus University Hospital, Department of Dermatology and Allergy Biederstein, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Service de pneumologie, Centre hospitalier de la région d'Annecy, Service de pneumo-allergologie, Centre Hospitalo-Universitaire de Béni-Messous, Allergy Centre, Vilnius University Antakalnis Hospital, Société Marocaine des Maladies Respiratoires, Centre of Respiratory Diseases and Allergy-Centre commercial Nadia, Allergy Division, Hospital S. João-Centre for Research in Health Technologies and Information Systems (CINTESIS)-Biostatistics and Medical Informatics Department-Porto University Medical School, Department of Otorhinolaryngology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of Social Medicine, University of Crete [Heraklion] (UOC)-Faculty of Medicine, Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Section of Allergology, Erasmus Medical Centre, Epidemiology and Biostatistics Division, University of Arizona-Associate Research Scientist, Respiratory Sciences-Arizona Respiratory Center, Helsinki University Hospital-Skin and Allergy Hospital, Centre Hospitalier de Bigorre [Tarbes]-Association Franco-Libanaise de Pneumologie (AFLP), Department of Otorhinolaryngology, Head, and Neck Surgery, University Hospital Leuven, Engineering and the Environment, University of Southampton, Paediatrics and Child Health, University College Cork (UCC), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de l'Asthme et des Allergies [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pediatric Allergy and Asthma Unit, Ihsan Dogramaci Children's Hospital-Hacettepe University School of Medicine, Institute for Asthma and Allergy, George Washington University Medical School, Department of Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth (USJ)-Faculté de Médecine-Hôtel-Dieu de France, Service des Maladies Respiratoires, CHU de Cocody-UFR des Sciences Médicales, Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Department of Clinical Immunology and Allergy, Medical University of Łódź (MUL)-Faculty ot Medicine, Centre for Allergy Research, Karolinska Institutet [Stockholm], Department of Clinical Science and Education, Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Hospital Medica Sur, Physiology Department, University of Medicine and Pharmacy, Division of Allergy Immunology, Department of Medicine-The University of Tennessee Health Science Center [Memphis] (UTHSC), university of dundee asthma - allergic rhinitis - COPD - beta-2-adrenoceptor, University of Dundee, Pulmonary and allergy unit, American University of Sharjah-Rashid Hospital-Dubai Health Authority (DHA), Association Franco-Vietnamienne de Pneumologie (AFVP), Centre Hospitalier de Compiègne (CHC), Arizona Respiratory Center, Department of Medicine, Clinical Immunology and Allergy, University of Mississippi Medical Center (UMMC), Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Allergy & Asthma Medical Group & Research Center, University of California [San Diego] (UC San Diego), Pneumology Department, Marius Nasta Institute of Pneumology, Department of Internal Medicine, Tishreen University School of Medicine, Association Franco-Marocaine de Pathologie Thoracique (AFMAPATH), Collège National des Pneumologues Marocains, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Immunoallergy Department, Hospital CUF Descobertas, Rhinology Unit & Smell Clinic, Universitat de Barcelona (UB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Allergy Unit, Università degli Studi di Padova = University of Padua (Unipd)-Department of Paediatrics, Section of Otolaryngology-Head & Neck Surgery (OHNS), University of Chicago, Clinique des maladies respiratoires, centre hospitalo-universitaire Mustapha Pacha d'Alger (CHUMA), Scientific Center for Children's Health, Russian Academy of Medical Sciences (RAMS), Laboratory of Allergology and Pulmonary Diseases, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Department of Pathology and Medical Biology-GRIAC Research Institute, ENT Department, University of Kinshasa (UNIKIN), Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust-Bradford Institute for Health Research, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital-Monash University Building, AMREP, Chiba University Hospital, Asthme Rhinite allergique, Pharmacie, Division of Pediatric Allergy and Immunology, marmara university, Pédiatrie, Centre Hospitalier National Pédiatrique Charles de Gaulle (CHNP-CDG), European Federation of Allergy (EFA), Airways Diseases Patients' Associations, Department of Allergology and Clinical Immunology, Charles University [Prague] (CU)-Medical Faculty in Pilsen, Immunopharmacology, Nippon Medical School-Medical Research Council Clinical, Laboratoire du Sommeil et de l'Effort, Société de Pneumologie de Langue Française (SPLF)-Clinique St George, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinic of Allergy and Asthma, Medical University Sofia-Alexander's University Hospital, Regional Health Service - Lazio, Primary Care Respiratory Medicine, University of Aberdeen-Department of General Practice and Primary Care-General Practice Airways Group (GPIAG), Department of Pulmonary Medicine, Leiden University Medical Center (LUMC), Pneumalgia, Centre Hospitalier Regional-Espace Francophone de Pneumologie (EFP)-Société de Pneumologie de l'Océan Indien (SPOI), Association Franco-Algérienne de Pneumologie (AFAP), Espace Francophone de pneumologie de la SPLF, Department of Pneumology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic de Barcelona-Institut Clínic del Tórax (ICT)-CIBER de Enfermedades Respiratorias (CIBERES)-University of Barcelona, Allergology and Clinical Immunology, Medical University of Silesia (SUM)-Chair and Clinical Department of Internal Diseases, UCSC-Allergy Unit, Complesso Integrato Columbus-Department of Internal Medicine and Geriatrics, Hospital da Luz, Medical Centre, Woodbrook Medical Centre, Research Fellow, University of Aberdeen-Department of General Practice, Centro Médico Docente La Trinidad, Department of Pharmacology, University College of London [London] (UCL)-The Royal National Throat, Nose and Ear Hospital, Primary Care Research & Development, University of Edinburgh-Centre for Population Health Sciences, Section of Allergy & Clinical Immunology, University of Manitoba [Winnipeg]-Department of Pediatrics & Child Health, Allergy Unit - Department of Dermatology, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], National Centre of Cardiology and Internal Medicine, Ministry of Health Kyrgyz Republic, School of Medicine, Pontifícia Universidade Católica, Department of ENT and Pediatrics, Finnish Institute of Occupational Health, Department of Obstetrics and Gynaecology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Christian Doppler Laboratory for Allergy Research, Medizinische Universität Wien = Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Department of Chest Medicine, Mont-Godinne Hospital-Catholic University of Louvain de Mont-Godinne, Department of Primary and Community Care, Radboud University Medical Center [Nijmegen], Epidemiology Unit, National Research Council (CNR)-Institute of Biomedicine and Molecular Immunology (IBIM), Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Department of Otolaryngology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, GLP Analytical Facility, School of Pharmacy, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna (MUW), Celal Bayar University School of Medicine, Allergy and Asthma Clinics, The Allergy and Asthma Institute, Department of Paediatrics and Child Health, Respiratory and Allergic Diseases, University Clinic of Respiratory and Allergic Diseases Golnik, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases-Guangzhou Medical College, Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], In collaboration with the WHO Collaborating Center for Asthma and Rhinitis, University of Genoa (UNIGE)-School of Specialization, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, University of Verona (UNIVR), Medical School-Federal University of Minas Gerais, University of Genoa (UNIGE)-Department of Internal Medicine (DIMI), University of California [Irvine] (UCI), University of California-University of California, Catholic University Rome, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre Hospitalier de Bigorre (Tarbes)-Association Franco-Libanaise de Pneumologie (AFLP), CUF-Descobertas Hospital, Universita degli Studi di Padova-Department of Paediatrics, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Centro Medico-Docente La Trinidad, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]-Instittute of Social Health, Department of Internal Medicine (DIMI)-University of Genoa (UNIGE), Medical University of Silesia-Chair and Clinical Department of Internal Diseases, Dermatology, Internal Medicine, Immunology, Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Research in Environmental Epidemiology ( CREAL ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universitat Pompeu Fabra [Barcelona], WHO(OMS), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), National Institute of Allergy and Infectious Diseases [Bethesda], National Institutes of Health ( NIH ), Swiss Institute of Allergy and Asthma Research ( SIAF ), University of Zürich [Zürich] ( UZH ), Upper Airway Research Laboratory ( URL ), University Medical Center, University of Oslo ( UiO ) -Oslo University Hospital, Charite-Universitatsmedizin Berlin [Berlin]-Instittute of Social Health, Medical School-Charité - University Medicine Berlin, Medical University of Warsaw-Faculté de Pharmacie de Paris, Ministry of Health, Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Public Health Research ( CSISP ), University of Genoa ( UNIGE ) -School of Specialization, University of Amsterdam [Amsterdam] ( UvA ) -Academic Medical Centre, University of Southampton [Southampton]-School of Medicine, Hôpital La Rabta [Tunis), Wake Forest University Health Sciences, CNR, Rome, Italy and Department of Medicine-Second University of Naples, Università degli Studi di Verona, Université Laval-l'Hôpital Laval, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, University of Genoa ( UNIGE ) -Department of Internal Medicine (DIMI), Southern California Research, Université Montpellier 1 ( UM1 ), Nova Southeastern University, Technische Universität München [München] ( TUM ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), University of Crete ( UOC ) -Faculty of Medicine, University of Southampton [Southampton], UUniversity College Cork - National University of Ireland, Cork (UCC), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], University of Groningen [Groningen]-University Medical Center Groningen-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth ( USJ ) -Faculté de Médecine-Hôtel-Dieu de France, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Medical University of Łódź ( MUL ) -Faculty ot Medicine, Medical University of Łódź ( MUL ) -Barlicki University Hospital, Department of Medicine-University of Tennessee College for Medicine, Association Franco-Vietnamienne de Pneumologie ( AFVP ), University of Mississippi Medical Center, University of California [San Diego] ( UC San Diego ), Association Franco-Marocaine de Pathologie Thoracique ( AFMAPATH ), Epidémiologie Environnementale : Impact Sanitaire des Pollutions ( EA 4064 ), Université Paris Descartes - Paris 5 ( UPD5 ), Universitat de Barcelona ( UB ) -Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Section of Otolaryngology-Head & Neck Surgery ( OHNS ), University of Groningen [Groningen]-University Medical Center Groningen-Department of Pathology and Medical Biology-GRIAC Research Institute, University Hospital of Kinshasa, European Federation of Allergy ( EFA ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Bioenergétique fondamentale et appliquée ( LBFA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of General Practice and Primary Care-General Practice Airways Group (GPIAG)-University of Aberdeen, Association Franco-Algérienne de Pneumologie ( AFAP ), Department of General Practice-University of Aberdeen, University College of London [London] ( UCL ) -The Royal National Throat, Nose and Ear Hospital, University Medical Center Utrecht, Faculty of Medicine-Laval University [Québec], Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, National University of Singapore ( NUS ) -Yong Loo Lin School of Medicine, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases ( DIAID ), Secretary General of the Global Allergy and Asthma European Network ( GA2LEN ), Network of Excellence, Charité - Universitätsmedizin Berlin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Universiteit Leiden-Universiteit Leiden, and Medizinische Universität Wien = Medical University of Vienna

Subjects
MESH: Asthma, severity, MESH: Comorbidity, Comorbidity, Severity of Illness Index, urticaria, MESH : Chronic Disease, MESH: Practice Guidelines as Topic, MESH : Dermatitis, Atopic, MESH: Urticaria, risk, 216-31 [Rhinitis, atopy, allergen Int Arch Allergy Immunol. 2012,158(3)], atopic dermatitis, MESH : Rhinitis, MESH: Rhinitis, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Effective primary care and public health [NCEBP 7], Immunoglobulin E - Asthma - Rhinitis - Rhinosinusitis - Urticaria - Atopic dermatitis, MESH : Practice Guidelines as Topic, Practice Guidelines as Topic, MESH : Comorbidity, MESH : Severity of Illness Index, IgE, MESH: Sinusitis, MESH : Urticaria, MESH: Hypersensitivity, macromolecular substances, MESH : Asthma, Dermatitis, Atopic, rhinitis, SDG 3 - Good Health and Well-being, MESH: Dermatitis, Atopic, MESH: Severity of Illness Index, Hypersensitivity, Humans, Sinusitis, rhinosinusitis, MESH : Hypersensitivity, MESH: Humans, MESH: Chronic Disease, MESH : Humans, Asthma, Atopic dermatitis, Immunoglobulin E, Rhinitis, Rhinosinusitis, Urticaria, asthma, allergy, MESH : Sinusitis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, control
Abstract

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies. Copyright (C) 2012 S. Karger AG, Basel

Published
2012

20. Development and implementation of guidelines in allergic rhinitis - an ARIA-GA2LEN paper

Author

Bousquet, J, Schünemann, Hj, Zuberbier, T, Bachert, C, Baena Cagnani CE, Bousquet, Pj, Brozek, J, Canonica, Giorgio, Casale, Tb, Demoly, P, Gerth van Wijk, R, Ohta, K, Bateman, Ed, Calderon, M, Cruz, Aa, Dolen, Wk, Haughney, J, Lockey, Rf, Lötvall, J, O'Byrne, P, Spranger, O, Togias, A, Bonini, S, Boulet, Lp, Camargos, P, Carlsen, Kh, Chavannes, Nh, Delgado, L, Durham, Sr, Fokkens, Wj, Fonseca, J, Haahtela, T, Kalayci, O, Kowalski, Ml, Larenas Linnemann, D, Li, J, Mohammad, Y, Mullol, J, Naclerio, R, O'Hehir, Re, Papadopoulos, N, Passalacqua, G, Rabe, Kf, Pawankar, R, Ryan, D, Samolinski, B, Simons, Fe, Valovirta, E, Yorgancioglu, A, Yusuf, Om, Agache, I, Aït Khaled, N, Annesi Maesano, I, Beghe, B, Ben Kheder, A, Blaiss, Ms, Boakye, Da, Bouchard, J, Burney, Pg, Busse, Ww, Chan Yeung, M, Chen, Y, Chuchalin, Ag, Costa, Dj, Custovic, A, Dahl, R, Denburg, J, Douagui, H, Emuzyte, R, Grouse, L, Humbert, M, Jackson, C, Johnston, Sl, Kaliner, Ma, Keith, Pk, Kim, Yy, Klossek, Jm, Kuna, P, Le, Lt, Lemiere, C, Lipworth, B, Mahboub, B, Malo, Jl, Marshall, Gd, Mavale Manuel, S, Meltzer, Eo, Morais Almeida, M, Motala, C, Naspitz, C, Nekam, K, Niggemann, B, Nizankowska Mogilnicka, E, Okamoto, Y, Orru, Mp, Ouedraogo, S, Palkonen, S, Popov, Ta, Price, D, Rosado Pinto, J, Scadding, Gk, Sooronbaev, Tm, Stoloff, Sw, Toskala, E, van Cauwenberge, P, Vandenplas, O, van Weel, C, Viegi, G, Virchow, Jc, Wang, Dy, Wickman, M, Williams, D, Yawn, Bp, Zar, Hj, Zernotti, M, Zhong, N, In collaboration with the WHO Collaborating Center of Asthma, Rhinitis, Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Photochimie moléculaire et macromoléculaire (PMM), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), P&A Kyriakou Children's Hospital, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), inconnu, Inconnu, Forschungszentrum Jülich GmbH - Projektträger BEO, GmbH, Laboratoire d'étude des textures et application aux matériaux (LETAM), Université Paul Verlaine - Metz (UPVM)-Centre National de la Recherche Scientifique (CNRS), Merlin Circuit Technology LTD, Institute for Meteorology and Climate Research (IMK), Karlsruhe Institute of Technology (KIT), Physics Department [UNB], University of New Brunswick (UNB), Bousquet J, Schünemann HJ, R Gerth van Wijk, K Ohta, Bateman ED, M Calderon, Cruz AA, Dolen WK, Haughney J, Lockey RF, Lötvall J, P O'Byrne, Zuberbier T, O Spranger, Togias A, S Bonini, LP Boulet, P Camargos, KH Carlsen, Chavannes NH, L Delgado, SR Durham, Fokkens WJ, C Bachert, Fonseca J, Haahtela T, O Kalayci, ML Kowalski, Larenas-Linnemann D, Li J, Y Mohammad, Mullol J, R Naclerio, RE O'Hehir, Baena-Cagnani CE, N Papadopoulos, G Passalacqua, KF Rabe, R Pawankar, Ryan D, B Samolinski, Simons FE, E Valovirta, Yorgancioglu A, Yusuf OM, Bousquet PJ, je Agache, Khaled N-Aït, Annesi-Maesano I, B Begge, Kheder Ben A, MS Blaiss, DA Boakye, Bouchard J, PG Burney, WW Busse, Brozek J, M Chan-Yeung, Y Chen, AG Chuchalin, Costa DJ, Custovic A, R Dahl, Denburg J, H Douagui, R Emuzyte, L Grouse, GW Canonica, M Humbert, C Jackson, SL Johnston, MA Kaliner, Keith PK, YY Kim, JM Klossek, P Kun, la tuberculose Casale, Demoly P, AII - Amsterdam institute for Infection and Immunity, Ear, Nose and Throat, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC), and Internal Medicine

Subjects
Evidence-Based Medicine, Rhinitis, Allergic, Perennial, MESH: Humans, treatment, MESH: Asthma, MESH: Rhinitis, Allergic, Perennial, rhinitis, asthma, guidelines, Disease Management, Rhinitis, Allergic, Seasonal, MESH: Rhinitis, Allergic, Seasonal, Planning Techniques, MESH: Planning Techniques, MESH: Disease Management, Asthma, MESH: Practice Guidelines as Topic, Practice Guidelines as Topic, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ARIA asthma EAACI EFA GA2LEN IPCRG rhinitis nonallergic rhinitis controlled-trial severe asthma randomized-trials consort statement primary-care 2008 update recommendations management quality, MESH: Evidence-Based Medicine
Abstract

International audience; The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

Published
2010

21. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision

Author

Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, and Schünemann HJ

Abstract

BACKGROUND: Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat the approximately 500 million affected patients globally. OBJECTIVE: To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. METHODS: The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. CONCLUSION: These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions.

Published
2010

22. Development and implementation of guidelines in allergic rhinitis – an ARIA-GA2LEN paper

Author

Bousquet J, Schünemann HJ, Zuberbier T, Bachert C, Baena-Cagnani CE, Bousquet PJ, Brozek J, Canonica GW, Casale TB, Demoly P, Gerth van Wijk R, Ohta K, Bateman ED, Calderon M, Cruz AA, Dolen WK, Haughney J, Lockey RF, Lötvall J, O'Byrne P, Spranger O, and Tog

Subjects
rhinitis, asthma
Abstract

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients’ values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

Published
2010

29. Probiotic prophylaxis of ventilator-associated pneumonia: a blinded, randomized, controlled trial.

Author

Morrow LE, Kollef MH, Casale TB, Morrow, Lee E, Kollef, Marin H, and Casale, Thomas B

Abstract

Rationale: Enteral administration of probiotics may modify the gastrointestinal environment in a manner that preferentially favors the growth of minimally virulent species. It is unknown whether probiotic modification of the upper aerodigestive flora can reduce nosocomial infections.Objectives: To determine whether oropharyngeal and gastric administration of Lactobacillus rhamnosus GG can reduce the incidence of ventilator-associated pneumonia (VAP).Methods: We performed a prospective, randomized, double-blind, placebo-controlled trial of 146 mechanically ventilated patients at high risk of developing VAP. Patients were randomly assigned to receive enteral probiotics (n = 68) or an inert inulin-based placebo (n = 70) twice a day in addition to routine care.Measurements and Main Results: Patients treated with Lactobacillus were significantly less likely to develop microbiologically confirmed VAP compared with patients treated with placebo (40.0 vs. 19.1%; P = 0.007). Although patients treated with probiotics had significantly less Clostridium difficile-associated diarrhea than patients treated with placebo (18.6 vs. 5.8%; P = 0.02), the duration of diarrhea per episode was not different between groups (13.2 ± 7.4 vs. 9.8 ± 4.9 d; P = 0.39). Patients treated with probiotics had fewer days of antibiotics prescribed for VAP (8.6 ± 10.3 vs. 5.6 ± 7.8 d; P = 0.05) and for C. difficile-associated diarrhea (2.1 ± 4.8 SD d vs. 0.5 ± 2.3 d; P = 0.02). No adverse events related to probiotic administration were identified.Conclusions: These pilot data suggest that L. rhamnosus GG is safe and efficacious in preventing VAP in a select, high-risk ICU population. Clinical trial registered with www.clinicaltrials.gov (NCT00613795). [ABSTRACT FROM AUTHOR]

Published
2010
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30. Should clinicians routinely determine rhinitis subtype on initial diagnosis and evaluation? A debate among experts [corrected] [published erratum appears in CLIN CORNERSTONE 2010;10(1):56].

Author

Quan M, Casale TB, and Blaiss MS

Abstract

Rhinitis is one of the most prevalent conditions affecting Americans today. Twenty to 40 million Americans (10%-30% of adults and up to 40% of children) are estimated to have allergic rhinitis. In recent decades, its prevalence in Western societies has increased dramatically, and studies from around the world are reporting similar trends. Although studies have traditionally reported a 3:1 ratio of allergic to nonallergic rhinitis, recent data suggest that as many as 87% of patients with rhinitis may have mixed rhinitis, a combination of both allergic and nonallergic rhinitis. Untreated or inappropriately managed rhinitis can significantly affect a patient's quality of life and ability to perform activities of daily living. It is often associated with concomitant conditions, such as fatigue, headache, sleep disturbance, cognitive impairment, and respiratory conditions, complicated by rhinitis, including asthma and sinusitis. It is a significant cause of morbidity, health care expenditure, reduced work productivity, and absences from school. According to the recently released updated practice parameters, The Diagnosis & Management of Rhinitis, rhinitis is characterized by the presence of one or more of the following nasal symptoms: Congestion, Rhinorrhea (anterior and posterior), Sneezing, Itching. Inflammation is normally associated with rhinitis, but certain subtypes of the disease, such as vasomotor (increasingly known as chronic idiopathic rhinitis) or nonallergic rhinitis and atrophic rhinitis, are not predominantly inflammatory. The diagnosis of rhinitis may appear to be a fairly straightforward undertaking; however, rhinitis is composed of numerous subtypes and etiologies, and differentiating them can be a challenge for primary care practitioners. Further complicating matters is the fact that many patients have both an allergic and a nonallergic component to their rhinitis. Whether or not identification of rhinitis subtype should be an integral component of initial diagnosis remains an area of controversy. While standard treatment for allergic and nonallergic rhinitis is often the same, certain subtypes of the disease do not respond well to the usual first-line treatments for allergic rhinitis. Identification of subtype, therefore, can potentially have important implications for treatment choice. In the following section, we present a discussion between 2 members of the Respiratory & Allergic Disease (RAD) Foundation, Thomas B. Casale, MD, and Michael S. Blaiss, MD. Drs. Casale and Blaiss debate the question, 'Should clinicians routinely determine rhinitis subtype on initial diagnosis and evaluation?' Each expert was randomly assigned a position to take: Dr. Casale's views represent the 'pro' argument while Dr. Blaiss was asked to speak to the 'con' argument. The debate concludes with a synthesis of their arguments and final points, including important takeaway messages for the primary care practitioner. [ABSTRACT FROM AUTHOR]

Published
2009
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31. Clinical importance of identifying immunoglobulin E-mediated disease in patients with asthma.

Author

Casale TB and Martin RJ

Abstract

The strong association between allergy and asthma is well documented; however, few practitioners-even asthma specialists-accurately estimate the percentage of patients with asthma who have clinically relevant allergies. Because allergen exposure can prompt airway inflammation, trigger asthma exacerbations, and possibly lead to negative health outcomes for patients with asthma, identifying allergies and immunoglobulin E (IgE)-mediated disease in patients with persistent asthma is crucial. Updated Expert Panel 3 asthma guidelines from the National Asthma Education and Prevention Program reinforce the need for clinicians to identify allergic sensitivities in patients with persistent asthma and determine their clinical relevance. Allergy testing can be useful in educating the patient with IgE-mediated asthma about the need for allergic trigger avoidance and can help determine optimal therapy for patients with concomitant asthma and allergy. Implementing this guideline recommendation, however, requires active clinical engagement. Data from a recent observational study indicate that there may be a substantial gap between guideline recommendations and actual clinical practice. These data also suggest that when clinicians participate in education about the role of IgE in asthma and begin testing their patients for allergy, the recognition of allergies among patients with asthma dramatically increases. [ABSTRACT FROM AUTHOR]

Published
2009
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33. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial.

Author

Casale TB, Condemi J, LaForce C, Nayak A, Rowe M, Watrous M, McAlary M, Fowler-Taylor A, Racine A, Gupta N, Fick R, Della Cioppa G, Omalizumab Seasonal Allergic Rhinitis Trial Group, Casale, T B, Condemi, J, LaForce, C, Nayak, A, Rowe, M, Watrous, M, and McAlary, M

Abstract

Context: Seasonal allergic rhinitis is a common IgE-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation.Objective: To assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis.Design: Randomized, double-blind, dose-ranging, placebo-controlled trial conducted from July 25 through November 21, 1997.Setting: Twenty-five outpatient centers throughout the United States.Patients: Five hundred thirty-six patients aged 12 to 75 years with at least a 2-year history of moderate to severe ragweed-induced seasonal allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL.Interventions: Patients were randomly assigned to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just prior to ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments).Main Outcome Measures: Self-assessed daily nasal symptom severity scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of treatment.Results: Nasal symptom severity scores were significantly lower in patients who received 300 mg of omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98, respectively; P =.002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during peak season. The frequency of adverse events was not significantly different among the omalizumab and placebo groups.Conclusion: Omalizumab decreased serum free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis. [ABSTRACT FROM AUTHOR]

Published
2001
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38. An approach to managing latex allergy in the health care worker.

Author

Muller BA, Steelman VM, Hartley PG, and Casale TB

Abstract

IgE-mediated sensitivity (true allergy) to latex occurs in well-defined groups. The common feature is a high degree of repeated exposure to latex. Approximately one percent of the total U.S. population and five to 17 percent of health care workers are affected. The objective of this article is to provide a rational approach to managing latex allergy in health care workers. Information is provided on the basis of a review of recent literature (primarily since 1986) and on the basis of work by the University of Iowa Hospitals and Clinics Multidisciplinary Latex Allergy Committee. This article summarizes a proactive, hospital-wide approach to effective management of latex allergy in health care workers. The approach incorporates recommendations from several review articles, including a position statement from the American College of Allergy Asthma, and Immunology and work done by the University of Iowa Hospitals and Clinics Multidisciplinary Latex Allergy Committee. Health care administrators, allergists, dermatologists, and occupational health personnel must work together to develop guidelines and implement policies to curb rising latex sensitization rates in health care workers. Many situations can be managed through medical, personal, and household avoidance of latex antigen and through modifications to the work environment. This article also presents an algorithmic approach to care management strategies that enhances documentation and yields more accurate data about incidence and prevalence of latex hypersensitivity among health care professionals. [ABSTRACT FROM AUTHOR]

Published
1998

39. Exercise-induced hypersensitivity syndromes in recreational and competitive athletes: a PRACTALL consensus report (what the general practitioner should know about sports and allergy)

Author

William R. Henderson, Timothy J. Craig, K-H. Carlsen, Tari Haahtela, Luís Delgado, Marta Ferrer, F Drobnic, Nikolaos G. Papadopoulos, Jan Lötvall, C C Randolph, André Moreira, R. G. Van Wijk, Antonino Romano, Lawrence B. Schwartz, Thomas B. Casale, S. Del Giacco, John M. Weiler, Sergio Bonini, Elliot Israel, Plastic and Reconstructive Surgery and Hand Surgery, Internal Medicine, Schwartz, Lb, Delgado, L, Craig, T, Bonini, Sergio, Carlsen, Kh, Casale, Tb, DEL GIACCO, S, Drobnic, F, VAN WIJK, Rg, Ferrer, M, Haahtela, T, Henderson, Wr, Israel, E, Lötvall, J, Moreira, A, Papadopoulos, Ng, Randolph, Cc, Romano, A, and Weiler, Jm

Subjects
medicine.medical_specialty, Allergy, Urticaria, Immunology, MEDLINE, Physical exercise, Competitive athletes, Hypersensitivity, medicine, Humans, Immunology and Allergy, Anaphylaxis, Exercise, Recreation, Rhinitis, Asthma, biology, business.industry, Athletes, Syndrome, medicine.disease, biology.organism_classification, Surgery, Asthma, Exercise-Induced, Family medicine, business
Abstract

Exercise-induced (EI) hypersensitivity disorders are significant problems for both recreational and competitive athletes. These include EI-asthma, EI-bronchoconstriction, EI-rhinitis, EI-anaphylaxis and EI-urticaria. A group of experts from the European Academy of Allergology and Clinical Immunology and the American Academy of Allergy Asthma and Immunology met to discuss the pathogenesis of these disorders and how to diagnose and treat them, and then to develop a consensus report. Key words (exercise with asthma, bronchoconstriction, rhinitis, urticaria or anaphylaxis) were used to search Medline, the Cochrane database and related websites through February 2008 to obtain pertinent information which, along with personal reference databases and institutional experience with these disorders, were used to develop this report. The goal is to provide physicians with guidance in the diagnosis, understanding and management of EI-hypersensitivity disorders to enable their patients to safely return to exercise-related activities.

Published
2008

41. Does angioedema in patients with chronic spontaneous urticaria impact response to omalizumab?

Author

Casale TB, Trzaskoma B, Holden M, Bernstein JA, and Maurer M

Abstract

The presence of angioedema, or deep skin swelling, in addition to hives (wheals) in patients with chronic spontaneous urticaria (CSU) can complicate disease management. There is evidence that omalizumab is effective for patients with CSU with angioedema, but the time to a clinically meaningful response has not been assessed. This post hoc analysis examined data from the phase 3, randomized, double-blind ASTERIA I and ASTERIA II studies: patients with CSU with hives were grouped by presence (n = 216) or absence of angioedema (n = 265) at baseline. The time to minimally important difference (MID, change from baseline of ≥11 points) in weekly Urticaria Activity Score (UAS7) was analyzed using Kaplan-Meier analyses. Median time to MID for omalizumab 300 mg was similar in patients with and without angioedema. Median time to MID for omalizumab 150 mg was similar to 300 mg for patients without angioedema, and was longer for patients with angioedema. Therefore, the response to omalizumab for patients with CSU with angioedema was dose dependent. We recommend that the best approach for clinicians, in line with guidelines, would be initial administration of omalizumab 300 mg every 4 weeks for all patients., Clinical Trials Registration: Clinicaltrials.gov NCT01287117 (registered 27 January 2011) and NCT01292473 (registered 7 February 2011)., Competing Interests: Thomas Casale is a consultant and speaker bureau member for Genentech, Inc.; consultant for Novartis Pharmaceuticals Corporation. Benjamin Trzaskoma and Michael Holden are employees of Genentech, Inc.; stockholders in Roche. Jonathan Bernstein is a consultant and PI for Genentech, Inc., Novartis, Amgen, GSK, Sanofi-Regeneron, AstraZeneca, Celldex, Allakos, Escient, Teva, Takeda/Shire, CSL Behring, Biocryst, Kalvista, Ionis, Biomarin, Pharming, Jasper. Marcus Maurer is a speaker and/or advisor for and/or has received research funding from Allakos, Alexion, Almirall, Alvotech, Amgen, Aquestive, Arcensus, argenX, AstraZeneca, Astria, BioCryst, Blueprint, Celldex, Celltrion, Clinuvel, Cogent, CSL Behring, Escient, Evommune, Excellergy, Genentech, GSK, Incyte, Jasper, Kashiv, Kalvista, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Mitsubishi Tanabe Pharma, Moxie, Noucor, Novartis, Orion Biotechnology, Pharvaris, Resonance Medicine, Sanofi/Regeneron, Santa Ana Bio, Septerna, Servier, Takeda, Teva, Third HarmonicBio, Valenza Bio, Vitalli Bio, Yuhan Corporation, Zurabio., (© 2024 The Authors.)

Published
2024
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42. Dupilumab Reduces Urticaria Activity, Itch, and Hives in Patients with Chronic Spontaneous Urticaria Regardless of Baseline Serum Immunoglobulin E Levels.

Author

Maurer M, Casale TB, Saini SS, Ben-Shoshan M, Laws E, Maloney J, Bauer D, Radin A, and Makhija M

Abstract

Introduction: In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total IgE above and below 100 IU/mL at baseline., Methods: Patients with H1-antihistamine-refractory CSU received dupilumab (n = 70) or placebo (n = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7 days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100 IU/mL at baseline., Results: Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: -31.9% (-41.9; -22.6); placebo: -6.3% (-21.3; 14.9)] and week 24 [dupilumab: -48.2% (-56.8; - 39.5); placebo: - 6.3% (-34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations (r < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes., Conclusions: Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms., Trial Registration: ClinicalTrials.gov Identifier: NCT04180488., (© 2024. The Author(s).)

Published
2024
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43. Dupilumab Reduces Exacerbations Independent of Changes in Biomarkers in Moderate-to-Severe Asthma.

Author

Pavord ID, Casale TB, Corren J, FitzGerald MJ, Deniz Y, Altincatal A, Gall R, Pandit-Abid N, Radwan A, Jacob-Nara JA, Rowe PJ, and Busse WW

Subjects
Humans, Male, Female, Adult, Middle Aged, Forced Expiratory Volume, Severity of Illness Index, Double-Blind Method, Treatment Outcome, Disease Progression, Leukocyte Count, Asthma drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Biomarkers, Eosinophils, Nitric Oxide metabolism, Anti-Asthmatic Agents therapeutic use
Abstract

Background: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma., Objective: This post hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854)., Methods: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV 1 ) at week 52 were performed as a function of the fold change in FeNO at week 52 and the maximum fold change in Eos over weeks 0-12 (also change from baseline in pre-BD FEV 1 at week 12)., Results: The combined placebo and dupilumab groups comprised 638 and 1264 patients, respectively. FeNO levels declined rapidly by week 2 and then gradually to week 52 in patients treated with dupilumab versus placebo; Eos, after initially increasing with dupilumab, declined slightly from baseline in both treatment groups. AER during QUEST showed no significant association with the change in biomarkers in either treatment group. The change from baseline in pre-BD FEV 1 at week 52 was inversely associated with the fold change in FeNO in both groups, with a significant difference between the dupilumab and placebo curves (P = .014), and was positively associated with the fold change in Eos in both groups (P = .022)., Conclusions: Relative changes in FeNO and Eos were not associated with AER, regardless of treatment arm. However, changes in both biomarkers showed a predictive value for lung function improvement; for FeNO, this was specific to the dupilumab treatment arm., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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44. Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, phase 3 trials.

Author

Maurer M, Casale TB, Saini SS, Ben-Shoshan M, Giménez-Arnau AM, Bernstein JA, Yagami A, Stjepanovic A, Radin A, Staudinger HW, Patel N, Amin N, Akinlade B, Fan C, Bauer D, Yancopoulos GD, Patel K, Mannent LP, and Laws E

Subjects
Humans, Adult, Female, Middle Aged, Male, Double-Blind Method, Adolescent, Omalizumab therapeutic use, Omalizumab adverse effects, Young Adult, Treatment Outcome, Aged, Child, Pruritus drug therapy, Anti-Allergic Agents therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Chronic Urticaria drug therapy
Abstract

Background: Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by recurrent pruritic wheals (hives) and/or angioedema. Patients with CSU could remain symptomatic despite standard-of-care H 1 antihistamines (H1-AH) or anti-IgE (omalizumab) treatment. Dupilumab blocks IL-4/IL-13 signaling and is approved for multiple type 2/atopic indications., Objective: We conducted two phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in patients with symptomatic CSU despite H1-AH., Methods: In LIBERTY-CSU CUPID Study A, patients were omalizumab-naive (n = 138, aged ≥6 years). In Study B, patients were omalizumab-intolerant/incomplete responders (n = 108, aged ≥12 years). The primary end point was either change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24, with the other as a key secondary end point, depending on regional regulatory requirements. Studies were pooled for safety assessment., Results: In Study A, UAS7 and ISS7 improved with dupilumab versus placebo (difference -8.5 [95% CI, -13.2 to -3.9; P = .0003] and -4.2 [95% CI, -6.6 to -1.8; P = .0005]). In Study B, tested at α = 0.043 after interim analysis, UAS7 improved (difference -5.8 [95% CI, -11.4 to -0.3; P = .0390]), with a numerical trend in ISS7 (difference -2.9 [95% CI, -5.7 to -0.07; nominal P = .0449, not significant]). Pooled safety data were consistent between dupilumab and placebo and with the known dupilumab safety profile., Conclusions: Dupilumab reduced urticaria activity by reducing itch and hives severity in omalizumab-naive patients with CSU uncontrolled with H1-AH. Although the primary end point for Study B was not met, dupilumab effects were small in patients who were omalizumab-intolerant/incomplete responders., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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45. Safety of 300IR house dust mite sublingual tablet from pooled clinical trial and post-marketing data.

Author

Worm M, Demoly P, Okamoto Y, Vidal C, Daghildjian K, Yan K, Casale TB, and Bergmann KC

Abstract

Background: The 300IR house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is approved for treatment of HDM-induced allergic rhinitis (AR). To provide a comprehensive review of the 300IR HDM-SLIT tablet safety profile based on randomized controlled trial (RCT) pooled data and post-marketing (PM) pharmacovigilance data., Methods: Subjects (5-65 years) with confirmed HDM-AR with or without controlled asthma were treated with 300IR or placebo in 8 RCTs. Reported treatment-emergent adverse events (TEAEs) were pooled and analyzed descriptively in subsets of adults/adolescents and children. Adverse reactions (ADRs) collected from spontaneous reporting and PM studies through a pharmacovigilance system since the first marketing authorization were also analyzed., Results: Across RCTs, 1853 subjects were treated with the 300IR HDM-SLIT tablet and 1846 with placebo. In both subsets of adults/adolescents and children whichever their asthma status, treatment-related TEAEs of higher incidence in active groups vs placebo were mostly consistent with mild or moderate local application-site reactions. They were mainly reported on the first days of treatment and decreased over time. 4 severe laryngopharyngeal reactions (2 requiring adrenaline/epinephrine) and 1 moderate eczema considered serious rapidly resolved with medications; no anaphylaxis was reported. In PM settings, ADRs reported in more than 235,000 patients were in line with RCT findings. Severe systemic reactions occurred rarely; 12 anaphylactic reactions resolved safely (5 with adrenaline). No new safety signal was raised., Conclusion: Safety data from RCTs and more than 7 years of real-life experience confirmed the favorable safety profile of 300IR HDM-SLIT tablet in patients across different regions, regardless of age and asthma status., Clinical Trial Registrations: NCT00674700; Retrospectively registered 06 May 2008.NCT01199133; Retrospectively registered 09 September 2010.NCT01527188; Retrospectively registered 01 February 2012.NCT02443805; Registered 29 April 2015/EudraCT 2014-004223-46; Registered 16 September 2015.jRCT2080221872/JapicCTI-121917; Registered 01 August 2012.jRCT2080222929/JapicCTI-15298; Registered 04 August 2015., Competing Interests: M. Worm reports consulting fees and payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing or educational events from Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Leo Pharma GmbH, AstraZeneca GmbH, ALK-Abelló Arzneimittel GmbH, Lilly Deutschland GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (a Viatris Company), Boehringer Ingelheim Pharma GmbH & Co. KG, GlaxoSmithKline GmbH & Co. KG, Almirall S. A., Pfizer Deutschland GmbH, Bristol-Myers Squibb GmbH & Co. KGaA and FomF GmbH, outside the submitted work. P. Demoly reports grants paid to his institutions from ALK-Abelló, AstraZeneca, GlaxoSmithKline, Menarini, Puressentiel, Stallergenes Greer, ThermoFisher Scientific, Viatris, and support for attending meetings and/or travel from Stallergenes Greer outside the submitted work. Y. Okamoto reports consulting fees and/or payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing or educational events from Torii Co., Ltd., Kirin Holding Co., Ltd., Stallergenes Greer, ALK-Abelló, Shionogi Co., Ltd., Yansen Co., Ltd., Tanabe-Mitsubishi Co., Ltd., Meiji Pharma, Novartis Co., Ltd.; support for attending meetings and/or travel from Torii Co., Ltd., Stallergenes Greer; participation on Data Safety Monitoring Board or Advisory Board from Stallergenes Greer, Kirin Holding Co., Ltd., Greer outside the submitted work. C. Vidal reports consulting fees paid to her institution from Stallergenes Greer, ALK- Abelló; honoraria from Stallergenes Greer; participation on Data Safety Monitoring Board or Advisory Board from Stallergenes Greer, Leti, ALK- Abelló, outside the submitted work. K. Daghildjian is an employee of Stallergenes Greer. K. Yan declares he has no conflicts of interests regarding the submitted work. T.B. Casale reports grants paid to his institution for conduct of original study from Stallergenes Greer. K.C. Bergmann reports payment for expert testimony, support for attending meetings and/or travel and participation on Data Safety Monitoring Board or Advisory Board from Bencard, Leti, Sanofi, GlaxoSmithKline, AstraZeneca, Novartis, Stallergenes Greer, HAL, outside the submitted work., (© 2024 The Authors.)

Published
2024
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46. Development of neffy , an Epinephrine Nasal Spray, for Severe Allergic Reactions.

Author

Ellis AK, Casale TB, Kaliner M, Oppenheimer J, Spergel JM, Fleischer DM, Bernstein D, Camargo CA Jr, Lowenthal R, and Tanimoto S

Abstract

Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy 's development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffy confirm the activation of α and β adrenergic receptors, which are the key components of epinephrine's mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis.

Published
2024
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47. Real-world outcomes in patients with chronic spontaneous urticaria receiving omalizumab: insights from a clinical practice survey.

Author

Seetasith A, Holden M, Hetherington J, Keal A, Salmon P, Bernstein JA, and Casale TB

Abstract

Objective: Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin condition, often impacting quality of life. International guidelines recommend omalizumab, an anti-immunoglobulin E antibody, for second-line treatment. Our objective was to understand patient characteristics associated with prescription of omalizumab, and assess real-world outcomes in patients with CSU treated with omalizumab., Methods: We analyzed data from the Adelphi Real World CSU Disease Specific Programme, a cross-sectional survey with retrospective data collection (December 2020-October 2021) from physicians and patients with CSU in the United States., Results: Data from allergists ( n  = 45), dermatologists ( n  = 51), and primary care physicians (PCPs; n  = 20) were included. At the time of data collection, one-third of patients were receiving omalizumab ( n  = 220) and 67% were eligible for but not receiving omalizumab ( n  = 455). Using logistic regression, the odds of receiving omalizumab were higher in patients whose entire bodies were affected by hives [odds ratio (OR) = 2.551; 95% confidence interval (CI) 1.502-4.333; p  < 0.001] or with deteriorating/unstable prognoses at treatment initiation [OR = 2.219; 95% CI 1.031-4.777; p  = 0.042], and lower in patients managed by PCPs [OR = 0.276; 95% CI 0.130-0.584; p  < 0.001]. Estimates from an inverse probability weighted regression adjustment model indicated that patients receiving omalizumab had higher treatment satisfaction, improvements in itching, hives, angioedema, insomnia, and anxiety, and lower impact on work productivity, compared with patients not receiving omalizumab., Conclusion: Around two-thirds of patients with CSU considered eligible for omalizumab were not receiving the guideline-recommended therapy. Patients receiving omalizumab had better real-world outcomes compared with patients not receiving omalizumab. Ensuring patients receive the most appropriate treatment could benefit patients with CSU.

Published
2024
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49. A practical guide for implementing omalizumab therapy for food allergy.

Author

Casale TB, Fiocchi A, and Greenhawt M

Subjects
Humans, Anaphylaxis drug therapy, Anaphylaxis immunology, Cost-Benefit Analysis, Drug Approval, Health Services Accessibility, Immunoglobulin E immunology, Immunotherapy, Treatment Outcome, Practice Guidelines as Topic, Food Hypersensitivity diagnosis, Food Hypersensitivity drug therapy, Food Hypersensitivity immunology, Omalizumab administration & dosage, Omalizumab immunology, Omalizumab pharmacology, Omalizumab therapeutic use, Anti-Allergic Agents administration & dosage, Anti-Allergic Agents immunology, Anti-Allergic Agents pharmacology, Anti-Allergic Agents therapeutic use
Abstract

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Published
2024
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