The reproducibility and sample size requirements of exercise-induced bronchoconstriction measurements

Dry air exercise challenges are frequently used to screen medications that have potential utility in the management of exercise-induced bronchoconstri ction (EIB), The purpose of this study was to determine the reproducibility of three outcome measurements made using such challenges, and sample size requirements for drug evaluation studies based on these outcomes. Forty adult subjects with asthma, who tested positively on a screening exer cise challenge, were subjected to two further identical challenges, separat ed by 1 to >35 days, Outcome measurements included the maximum per cent fal l in forced expiratory volume in one second (FEV1), after exercise (% fallm ax), and the area under the per cent fall in FEV1/time curve for 30 min (AU C30) and 60 min (AUC60) after exercise, The reproducibility of these outcomes, as assessed by intraclass correlatio n coefficients was 0.72, 0.53 and 0.35 for % fallmax, AUC30 and AUC60 measu rements, respectively. The sample size requirements to demonstrate an atten uation of EIB equivalent to a 50% reduction in % fallmax was 9, 14 and 19 s ubjects for the % fallmax, AUC30 and AUC60 responses, respectively (90% pow er), It is concluded that the maximum percentage fall in forced expiratory volum e in one second has greater reproducibility and results in greater power in clinical trials than area under the curve measurements, Sample size calcul ation curves are provided which may he used in study design and interpretat ion of published studies.