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

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 PD(20) 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 (FEV(1)) >70% pred., PD(20) <3.9 micromol 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 micromol or > or =40% decline in FEV(1)) were repeated every 4 weeks and after wash-out. The main study objectives were changes from baseline in maximal FEV(1) decline at the response plateau (i.e. >2 post-dose FEV(1) values within 5%) and PD(20) to methacholine after 12 weeks' treatment. RESULTS: Neither treatment affected baseline FEV(1) (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 FEV(1) decline (mean change in FEV(1) decline was 2.1% [montelukast] and -0.8% [placebo], respectively, P<0.05), and increased PD(20) methacholine (mean change in PD(20) 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).