Add-on montelukast to inhaled corticosteroids protects against excessive airway narrowing

Abstract

Rationale: Excessive airway narrowing in response to broncho-active stimuli is a predictor for severe exacerbations in asthma. Leukotriene receptor antagonists (LTRAs) have complementary properties to inhaled corticosteroids (ICS) on asthma control. Objectives: The LTRA montelukast may provide an additional protection against excessive airway narrowing. We tested the add-on effects of montelukast on the maximal response plateau and PD20 to inhaled methacholine in asthmatics on a stable dose of ICS. Methods: Thirty-one patients with allergic asthma [14M/17F, 19-50 years, forced expiratory volume in 1 s (FEV1) >70% pred., PD20 <3.9 μmol methacholine], with a twice documented response plateau to methacholine, were randomized in a double-blind (montelukast 10 mg or matching placebo once daily), 12-week parallel study. Bronchoprovocation tests with methacholine (0.03-256 μmol or ≥40% decline in FEV1) were repeated every 4 weeks and after wash-out. The main study objectives were changes from baseline in maximal FEV1 decline at the response plateau (i.e. >2 post-dose FEV 1 values within 5%) and PD20 to methacholine after 12 weeks' treatment. Results: Neither treatment affected baseline FEV1 (P=0.62). Compared with placebo, montelukast significantly decreased the maximal response plateau to methacholine (mean difference 9.4%; 95% confidence interval 3.9-15.7; P<0.005), improved the FEV1 decline (mean change in FEV1 decline was 2.1% [montelukast] and -0.8% [placebo], respectively, P<0.05), and increased PD20 methacholine (mean change in PD20 of 5.3 [montelukast] and 1.4 [placebo] doubling doses, respectively, P<0.001). Conclusion: Add-on montelukast to ICS has disease-modifying effects in adults with persistent asthma, and hence reduces the risk of excessive airway narrowing (NCT 00913328). © 2010 Blackwell Publishing Ltd.