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

SummaryBackgroundExamination 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.ObjectivesOur 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.MethodsAdult 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.ResultsChange 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).ConclusionDirect examination of airway tissue confirms that montelukast decreases the number of eosinophils and mast cells in asthma.