title: Inhaled allergen bronchoprovocation tests.
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.
authors.affiliation: Department of Respiratory Medicine and Allergology, Skane University, Lund, Sweden; Department of General Practice, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Diamant
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.forename: Don W
authors.initials: DW
authors.lastname: Cockcroft
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: Frans H C
authors.initials: FH
authors.lastname: de Jongh
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D001249:Asthma / Q000175:diagnosis* / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001985:Bronchial Provocation Tests; D006801:Humans
chemical_list: D000485:Allergens
keywords: AHR; APC(20); AUC; Airway hyperresponsiveness; Allergen challenge; Allergen concentration causing a decrease in FEV(1) of 20% from baseline; Area under the curve; EAR; Early asthmatic (allergic) response; Exhaled nitric oxide; LAR; Late asthmatic (allergic) response; SOP; Standard operating procedure; asthma; drug development; eNO; methodology