Repeatability of allergen-induced airway inflammation☆☆☆★

Abstract 

Background: Allergen inhalation challenge is a useful clinical model to investigate the effects of asthma therapies on allergen-induced airway responses; however, the repeatability of allergen-induced airway inflammation is not known. Objective: The purpose of this study was to investigate the repeatability of allergen-induced increases in sputum eosinophils. This information will allow the prediction of the number of subjects required in studies evaluating asthma therapies. Methods: Seventeen subjects completed 2 allergen challenges using the same dose of allergen, at least 3 weeks apart. Allergen-induced airway responses were measured for 7 hours after challenge. Differential cell counts from induced sputum were determined the day before and 7 and 24 hours after challenge; methacholine PC ₂₀ was measured the day before and 24 hours after challenge. Results: The intraclass correlation coefficient for maximum percent late fall in FEV ₁ was 0.32 and for the area of the late response was 0.61. The sample size predicted to be necessary to observe 50% attenuation of the maximum percent late fall in FEV ₁ and the late area under the curve with a power of 0.95 was 9 subjects. The intraclass correlation coefficient for percent of allergen-induced sputum eosinophils was 0.60 at 7 hours and 0.53 at 24 hours after challenge. With a randomized cross-over study design, the sample size predicted to be necessary to observe 50% attenuation of allergen-induced percent of eosinophils with a power of 0.95 was 5 subjects. Conclusion: Allergen inhalation challenge with measurements of sputum eosinophils is a noninvasive and reliable method for evaluating the anti-inflammatory effects of asthma therapies. (J Allergy Clin Immunol 1999;104:66-71.)

Keywords:  Allergen challenge, sputum eosinophils, reproducibility, sample size, anti-inflammatory therapy

Abbreviations:  AUC , Area under the curve, GSEM , Geometric standard error of the mean, ICC , Intraclass correlation coefficient, MCC , Metachromatic cell