Formoterol induces tolerance to the bronchodilating effect of Salbutamol following methacholine-provocation test in asthmatic children

Objectives: To study whether Formoterol treatment affect the bronchodilator response to salbutamol after methacholine-provocation test (MPT) in asthmatic children. Study design: A prospective, double-blind, randomized, placebo-controlled study. Children aged 7-16 years with mild-persistent to moderate asthma treated with inhaled corticosteroids, were enrolled. After 2-weeks of run-in period, subjects were randomized to inhaled Formoterol 9 μg bid (n=19) or placebo (n=19) for 2 weeks. MPT with salbutamol-recovery curve was performed at the beginning and at the end of the trial period. Measurements of peak expiratory flow rate (PEFR), symptoms score, rescue bronchodilator usage and side effects were recorded daily. The primary end-points were the change in FEV₁ 0-10 min after salbutamol inhalation and the recovery time from 80 to 100% of pretest FEV₁. Statistical analyses were performed by ANOVA with repeated measures. Results: There was a decrease in the bronchodilator response to salbutamol and an improved PEFR in the Formoterol group. There was no difference in all other parameters. Conclusion: Formoterol decreases the bronchodilator response to salbutamol following MPT. Whether this phenomenon has clinical implication during acute asthma needs further studies.