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

Summary 

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 ≤4mg/mL) were given 10mg/day oral montelukast (N=38) or placebo (N=37) for 6weeks. 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 13.54cells/mm (at baseline) to 0.79cells/mm at 6weeks 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.

Keywords: Asthma, Eosinophils, Inflammation, Leukotrienes, Receptors