TOLERANCE TO THE BRONCHOPROTECTIVE EFFECT OF SALMETEROL IN ADOLESCENTS WITH EXERCISE-INDUCED ASTHMA USING CONCURRENT INHALED GLUCOCORTICOIDTREATMENT

Objectives. The long-acting beta(2)-adrenergic agonist salmeterol prev ents exercise-induced asthma, but tolerance may develop to its broncho protective effect. We wanted to ascertain if the development of tolera nce 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 ado lescents receiving regular glucocorticoid inhalations. Methods. In a r andomized, double-blind, 2x28-day crossover study, we administered sal meterol (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 inhalat ion on the 1st and 28th day of each treatment period. The primary outc ome variable was the maximum decrease in percent predicted FEV1 postex ercise. Results. Fourteen subjects with a mean age of 13.1 years compl eted the study. The first dose of salmeterol had an excellent bronchop rotective effect against exercise-induced asthma at 1 and 9 hours. Aft er the 28th consecutive daily dose of salmeterol, the bronchoprotectiv e 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 o f salmeterol has an excellent protective effect against exercise-induc ed asthma for at least 9 hours, but that this effect may wane during r egular once-daily salmeterol treatment, despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids.