Montelukast and bronchial inflammation in asthma: A randomised, double-blind placebo-controlled trial

Background: Examination of bronchoalveolar lavage, induced sputum, and peripheral blood indicate that cysteinyl leukotriene receptor blockers decrease inflammatory cells in asthma but these do not examine airway tissue per se. Objectives: Our objective was to determine the effect of montelukast, a leukotriene receptor antagonist, on airway tissue inflammatory cells by direct bronchoscopic examination of the bronchial mucosa. Methods: Adult subjects with mild asthma (pre-bronchodilator FEV₁ ≥ 70% predicted; PC₂₀ of ≤4 mg/mL) were given 10 mg/day oral montelukast (N = 38) or placebo (N = 37) for 6 weeks. Bronchial mucosal eosinophils and mast cells were identified and counted. Results: Change from baseline in numbers of biopsy EG2+ ("activated") eosinophils was the primary endpoint; numbers of total (chromotrope 2R+) eosinophils and (tryptase+) mast cells were secondary. Unexpectedly, there were many patients with zero EG2+ eosinophils at baseline. There was a within-group decrease in EG2+ cells, from 13.54 cells/mm (at baseline) to 0.79 cells/mm at 6 weeks in the montelukast group (LS mean change; 95% confidence interval = -13.59 [-25.45, -1.74] cells/mm; P < 0.05), a change not observed in the placebo group (-1.17 [-13.26, 10.91] cells/mm; NS). The zero-inflated Poisson statistical model demonstrated that montelukast significantly reduced post-treatment EG2+ cells by 80% compared with placebo (95% CI [70.6-86.8%]; P < 0.0001). The data for total eosinophils showed similar changes. The reduction in mast cell numbers was 12% (95% CI [7.9, 16.0]; P < 0.0001). Conclusion: Direct examination of airway tissue confirms that montelukast decreases the number of eosinophils and mast cells in asthma.