Prevention of exercise-induced bronchospasm in pediatric asthma patients: a comparison of salmeterol powder with albuterol

Background: Exercise-induced bronchospasm (EIB) is a common problem in children with asthma. Pretreatment with the beta(2) (beta(2))-adrenoreceptor agonist albuterol is effective for preventing EIB, but is recognized as providing only short-term (2 to 3 hour) protection. Objective: To evaluate the 12-hour efficacy and safety of single doses of 25 mu g and 50 mu g of salmeterol powder administered via Diskus(R) inhaler versus albuterol aerosol via pressurized metered-dose inhaler and placebo in preventing EIB in asthmatic children. Methods: A randomized, double-blind, placebo-controlled, double-dummy, single-dose, four-way crossover study was conducted in pediatric patients (4 to 11 years of age) demonstrating EIB and mild-to-moderate asthma. Serial forced expiratory volume in 1 second (FEV1) was measured before and after standard treadmill exercise at hour 1, hour 6, and hour 12 after administration of 25 mu g or 50 mu g salmeterol powder, 180 mu g albuterol aerosol, or placebo. Adverse events were recorded. Results: After completion of the hour 1 exercise challenge, mean minimum % predicted FEV1 was significantly higher following albuterol (91.3%) than for placebo (75.3%) and for both dosages of salmeterol (86.9% and 85.8% for salmeterol 25 mu g and 50 mu g, respectively; P less than or equal to .026). After completion of both the hour 6 and hour 12 exercise challenges, the 50-mu g salmeterol treatment produced a significantly higher mean minimum percent of predicted FEV1 (90.6% and 87.3% predicted, respectively) than the mean minimum percent of predicted FEV1 for placebo or albuterol (73.8% to 78.4% of predicted; P less than or equal to .041). At hour 6, the 25-mu g salmeterol treatment was not significantly different from albuterol or placebo. At hour 12, the 25-mu g salmeterol treatment mean minimum percent of predicted was significantly higher than albuterol (87.9% versus: 73.8% of predicted; P = .006) and there was also a trend toward significance over placebo (76.9% predicted; P = .056). At all exercise periods, no statistically significant differences in spirometry values were observed between the two salmeterol treatment groups. Safety profiles were similar among treatments, including placebo. No drug-related adverse events or withdrawals due to adverse events occurred. Changes in laboratory values, vital signs, 12-lead ECGs, and physical examinations were unremarkable. Conclusions: A single 50-mu g dose of salmeterol powder provided effective and safe protection against EIB for at least 12 hours in asthmatic children and provided a significantly more prolonged effect than albuterol aerosol (180 mu g).