Combination drug therapy for the prevention of exercise-induced bronchoconstriction in children

Background: Sequential administration of a beta-agonist and cromolyn or nedocromil before exercise is recommended for patients whose symptoms are not controlled by beta-agonists alone; however, this practice reduces compliance. Objective: To evaluate the effectiveness of a new pre-combined aerosol formulation (salbutamol and nedocromil) in preventing exercise-induced bronchoconstriction and to compare it to salbutamol alone. Methods: Twelve children with asthma were studied in a double-blind, double-dummy, randomized, crossover, placebo-controlled design to compare the protective effect of salbutamol and a new pre-combined salbutamol/nedocromil formulation against exercise-induced bronchoconstriction. The drugs were delivered by a metered-dose inhaler (salbutamol, 200 mu g; salbutamol/nedocromil, 200 mu g/4 mg; placebo, 2 puffs) 20 minutes before exercise. Results: Both active drugs were significantly more protective than placebo but there was no difference between them. Complete protection was obtained in 12/12, 10/12, and 1/12 subjects for the salbutamol/nedocromil combination, salbutamol alone and placebo, respectively. Conclusions: Although inhaled beta-agonists alone are highly efficacious in preventing exercise-induced bronchoconstriction, a minority of patients exists for whom a combined treatment with salbutamol and nedocromil is advantageous. This group may represent a subpopulation of subjects who release more, or different, mediators in response to exercise.