Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment

Objectives. The long-acting beta(2)-adrenergic agonist salmeterol prevents exercise-induced asthma, but tolerance may develop to its bronchoprotective effect. We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 mu g once daily, instead of the usual dose of 50 mu g twice daily, in adolescents receiving regular glucocorticoid inhalations. Methods. In a randomized, double-blind, 2x28-day crossover study, we administered salmeterol (50 mu g) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance. Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period. The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise. Results. Fourteen subjects with a mean age of 13.1 years completed the study. The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours. After the 28th consecutive daily dose of salmeterol, the bronchoprotective effect was significantly greater than that of placebo at 1 hour, but not at 9 hours. Conclusions. We conclude that a single 50-mu g dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours, but that this effect may wane during regular once-daily salmeterol treatment, despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids.