Montelukast treatment attenuates the increase in myofibroblasts following low-dose allergen challenge.
BACKGROUND
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.
Kelly
Margaret M
MM
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Chakir
Jamila
J
Vethanayagam
Dilini
D
Boulet
Louis-Philippe
LP
Laviolette
Michel
M
Gauldie
Jack
J
O'Byrne
Paul M
PM
D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D011014:Pneumonia / Q000473:pathology / Q000503:physiopathology; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; C093875:montelukast