Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial.
Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.
Pizzichini
E
E
Asthma Research Group, St. Joseph's Hospital-McMaster University, Hamilton, Ontario, Canada.
Leff
J A
JA
Reiss
T F
TF
Hendeles
L
L
Boulet
L P
LP
Wei
L X
LX
Efthimiadis
A E
AE
Zhang
J
J
Hargreave
F E
FE
D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003521:Cyclopropanes; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011804:Quinolines / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D012140:Respiratory Tract Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012449:Safety; D013183:Sputum / Q000166:cytology / Q000187:drug effects; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast