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Montelukast Treatment Attenuates the Increase in Myofibroblasts Following Low-Dose Allergen Challenge^*

^* From the Department of, Pathology and Molecular Medicine (Drs. Kelly and Gauldie) and the Department of Medicine (Drs. Vethanayagam and O’Byrne), McMaster University, Hamilton, Ontario; and Centre de recherche (Drs. Chakir, Boulet, and Laviolette), Hôpital Laval, Institut universitaire de cardiologie et de pneumologie, Sainte-Foy, Québec, Canada.

Correspondence to: Paul O’Byrne, MD, FCCP, Department of Medicine, McMaster University Medical Centre, Room, 1200 Main St W, Hamilton, Ontario L8N 3Z5, Canada; e-mail: obyrnep{at}mcmaster.ca

Abstract

Rationale: Airway remodeling is believed to be important in the pathophysiology of asthma, and myofibroblasts are increased in the airways of asthmatic individuals 24 h after allergen challenge. Leukotriene receptor antagonists exert antiinflammatory activity in asthma, but it is unknown whether they influence indices of airway remodeling. In the present study, we evaluated the effect of montelukast on airway myofibroblasts following low-dose allergen challenge (LDAC).

Methods: Stable subjects with mild asthma were included in a two-center, randomized, parallel-group study. A 2-week run-in period was followed by LDAC and endobronchial biopsy. Subjects were then randomized to receive either montelukast, 10 mg/d, or placebo (n = 10 in each group) for 8 weeks in a double-blind manner; at the end of the treatment period, subjects underwent a second LDAC and endobronchial biopsy. The effect of treatment on myofibroblasts, fibroblasts, and inflammatory cells was examined using electron microscopy techniques.

Results: Treatment with montelukast showed no significant difference by comparison with placebo but did show a significant within-group treatment-related decrease in airway wall myofibroblasts not seen in the placebo group. In addition, the montelukast-treated group also showed a significant within-group reduction in lymphomononuclear cells and increased neutrophils.

Conclusions: The results suggest that montelukast has an inhibitory effect on airway structural cells that play a key role in airway remodeling in allergic airway inflammation, and that montelukast may be a useful therapy to attenuate airway remodeling in asthma.

Key Words: airway remodeling • allergen challenge • asthma • leukotriene receptor antagonist • myofibroblast

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