title: Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma.
abstract: Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (> or =5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, i.e. 75th-25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.
authors.affiliation: Firestone Institute for Respiratory Health, St. Joseph's Healthcare, 50 Charlton Ave. E., Hamilton, ON L8N 4A6, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Jayaram
authors.forename: M
authors.initials: M
authors.lastname: Duong
authors.forename: M M M
authors.initials: MM
authors.lastname: Pizzichini
authors.forename: E
authors.initials: E
authors.lastname: Pizzichini
authors.forename: D
authors.initials: D
authors.lastname: Kamada
authors.forename: A
authors.initials: A
authors.lastname: Efthimiadis
authors.forename: F E
authors.initials: FE
authors.lastname: Hargreave
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004802:Eosinophilia / Q000188:drug therapy*; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D011336:Probability; D011804:Quinolines / Q000627:therapeutic use*; D012016:Reference Values; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology / Q000187:drug effects; D013440:Sulfides; D017211:Treatment Failure
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast; D011241:Prednisone