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 bronchoconstriction (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 exercise challenge, were subjected to two further identical challenges, separated by 1 to >35 days. Outcome measurements included the maximum per cent fall in forced expiratory volume in one second (FEV1), after exercise (% fallmax), and the area under the per cent fall in FEV1/time curve for 30 min (AUC30) and 60 min (AUC60) after exercise. The reproducibility of these outcomes, as assessed by intraclass correlation coefficients was 0.72, 0.53 and 0.35 for % fallmax, AUC30 and AUC60 measurements, respectively. The sample size requirements to demonstrate an attenuation of EIB equivalent to a 50% reduction in % fallmax was 9, 14 and 19 subjects for the % fallmax, AUC30 and AUC60 responses, respectively (90% power). It is concluded that the maximum percentage fall in forced expiratory volume in one second has greater reproducibility and results in greater power in clinical trials than area under the curve measurements. Sample size calculation curves are provided which may be used in study design and interpretation of published studies.
Dahlén
B
B
Dept of Medicine at Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
O'Byrne
P M
PM
Watson
R M
RM
Roquet
A
A
Larsen
F
F
Inman
M D
MD
D000328:Adult; D001250:Asthma, Exercise-Induced / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000502:physiology*; D004341:Drug Evaluation; D005541:Forced Expiratory Volume; D006801:Humans; D015203:Reproducibility of Results; D018401:Sample Size