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Inhaled allergen bronchoprovocation tests - 30/10/13

Doi : 10.1016/j.jaci.2013.08.023 
Zuzana Diamant, MD, PhD a, b, Gail M. Gauvreau, PhD c, Don W. Cockcroft, MD, FRCPC, FAAAAI d, Louis-Philippe Boulet, MD, FRCP(C) e, Peter J. Sterk, MD, PhD f, Frans H.C. de Jongh, PhD f, Barbro Dahlén, MD, PhD g, Paul M. O’Byrne, MB, FRCP(C) c,
a Department of Respiratory Medicine and Allergology, Skane University, Lund, Sweden 
b Department of General Practice, University Medical Centre Groningen, Groningen, The Netherlands 
c Department of Medicine, McMaster University, Hamilton, Ontario, Canada 
d Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada 
e Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada 
f Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands 
g Department of Respiratory Medicine and Allergy, Karolinska Institute, Centre for Allergy Research, Karolinska University Hospital, Stockholm, Sweden 

Corresponding author: Paul M. O’Byrne, MB, FRCP(C), McMaster University, HSC 3W10, 1280 Main St West, Hamilton, Ontario L8S 4K1, Canada.

Abstract

The allergen bronchoprovocation test is a long-standing exacerbation model of allergic asthma that can induce several clinical and pathophysiologic features of asthma in sensitized subjects. Standardized allergen challenge is primarily a research tool, and when properly conducted by qualified and experienced investigators, it is safe and highly reproducible. In combination with validated airway sampling and sensitive detection techniques, allergen challenge allows the study of several features of the physiology of mainly TH2 cell–driven asthma in relation to the kinetics of the underlying airway pathology occurring during the allergen-induced late response. Furthermore, given the small within-subject variability in allergen-induced airway responses, allergen challenge offers an adequate disease model for the evaluation of new (targeted) controller therapies for asthma in a limited number of subjects. In proof-of-efficacy studies thus far, allergen challenge showed a fair positive predicted value and an excellent negative predictive value for the actual clinical efficacy of new antiasthma therapies, underscoring its important role in early drug development. In this review we provide recommendations on challenge methods, response measurements, sample size, safety, and harmonization for future applications.

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Key words : Allergen challenge, methodology, asthma, drug development

Abbreviations used : AHR, APC20, AUC, EAR, eNO, LAR, SOP


Esquema


 Disclosure of potential conflict of interest: Z. Diamant works part time at a CRO (QPS Netherlands, Groningen, NL) and has received one or more grants from or has one or more grants pending with MSD, Biomedical Systems, and Benecke BV. G. M. Gauvreau has been supported by one or more grants from Genentech and CSL and has received one or more consulting fees or honoraria from ONO and AIM Therapeutics. D. W. Cockcroft has received one or more grants from or has one or more grants pending with ONO, Novartis, Amgen, and Genentech and has received royalties for allergen and methacholine challenge standard operating procedures. B. Dahlén has consultancy arrangements with Actelion, has received one or more payments for lecturing from or is on the speakers' bureau for Meda and Novartis, and has received royalties from Studentlitteratur. P. M. O'Byrne has been supported by one or more grants from AIM, AstraZeneca, Amgen, GlaxoSmithKline, ONO, Genentech, and Novartis; has received one or more consulting fees or honoraria from AstraZeneca, GlaxoSmithKline, Merck, and Novartis; and has received one or more fees for participation from the Joint Oversight Board for LABA safety study. The rest of the authors declare that they have no relevant conflicts of interest.


© 2013  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 132 - N° 5

P. 1045 - novembre 2013 Regresar al número
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