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 evaluate 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 forced expiratory volume in 1 second [FEV₁]) 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 β₂-agonist alone or low-to-medium dose inhaled corticosteroid plus as-needed short-acting β₂-agonist). FEV₁ was measured 5 minutes pre-dose, 30 minutes postdose (5 minutes pre-exercise challenge [baseline]), and 5, 10, 15, 30, and 60 minutes postexercise. The primary end point was maximum percentage fall from baseline in FEV₁ up to 60 minutes postexercise challenge.

Results: Least squares mean maximum percentage fall in FEV₁ up to 60 minutes postexercise challenge was 5.45% with albuterol/budesonide vs 18.97% with placebo (difference, -13.51% [95% confidence interval, -16.94% to -10.09%]; P < .001). More subjects were fully protected (maximum percentage fall in FEV₁ post-exercise challenge < 10%) with albuterol/budesonide than with placebo (78.3% vs 28.3%; P < .001). The treatment effect was consistent irrespective of background inhaled corticosteroid 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 before exercise was significantly more effective than placebo in preventing EIB.

Trial registration: ClinicalTrials.gov Identifier: NCT04234464.