Albuterol/budesonide for the treatment of exercise-induced bronchoconstriction in patients with asthma: the TYREE study

Background: PT027 is a fixed-dose combination of albuterol (salbutamol) and budesonide in a single pressurized metered dose inhaler. Objective: To assess the efficacy and safety of albuterol/budesonide compared with placebo in patients with asthma and exercise-induced bronchoconstriction (EIB). Methods: In this randomized, double-blind, 2-period, single-dose crossover study, adolescents and adults with asthma and EIB (defined by ≥20% decrease from pre-exercise challenge FEV 1) were randomized to albuterol/budesonide (180/160 µg) followed by placebo (n=29) or the reverse sequence (n=31). Subjects were stratified by background therapy (as-needed short-acting β 2 -agonist [SABA] alone or low- to medium-dose inhaled corticosteroid [ICS] plus as-needed SABA). FEV 1 was measured 5 minutes pre-dose, 30 minutes post-dose (5 minutes pre-exercise challenge [baseline]), and 5, 10, 15, 30 and 60 minutes post-exercise. The primary endpoint was maximum percentage fall from baseline in FEV 1 up to 60 minutes postexercise challenge. Results: Least squares mean maximum percentage fall in FEV 1 up to 60 minutes postexercise challenge was 5.45% with albuterol/budesonide versus 18.97% with placebo (difference -13.51% [95% CI: -16.94%, -10.09%]; p<0.001). More subjects were fully protected (maximum percentage fall in FEV 1 post-exercise challenge <10%) with albuterol/budesonide than with placebo (78.3% vs 28.3%; p<0.001). The treatment effect was consistent irrespective of background ICS therapy, and albuterol/budesonide was well tolerated. Conclusion: In adolescents and adults with asthma and EIB, a single dose of albuterol/budesonide 180/160 µg taken approximately 30 minutes prior to exercise was significantly more effective than placebo in preventing EIB