title: Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma.
abstract: We evaluated whether montelukast conferred additive effects in patients with asthma receiving fluticasone/salmeterol (FP/SM) combination and FP alone. Twenty-two patients with mild to moderate asthma completed a double-blind, placebo-controlled study. After a 2-week run-in using FP 250 microg/SM 50 microg 1 puff twice daily, patients entered a randomized crossover period to receive additional montelukast 10 mg daily or placebo for 3 weeks each. For the first 2 weeks, they received FP/SM 1 puff BID, and then they received FP 250 microg 1 puff BID for the 3rd week. The primary outcome was adenosine monophosphate challenge threshold and recovery time; secondary outcomes included surrogate inflammatory markers and lung function. Compared with FP/SM run-in, adding montelukast to FP/SM was better (p < 0.05) than placebo for inflammatory markers but not for lung function. For adenosine monophosphate threshold, recovery, exhaled nitric oxide, and blood eosinophils, there were 1.4 (95% confidence interval, 1.1-1.8) geometric mean fold, 10 minutes (3-17 minutes), 2.1 parts per billion (0.2-3.9 parts per billion), and 88 (34-172) x 10(6)/L differences, respectively. The combination of FP plus montelukast was superior to FP/SM for inflammatory markers but was inferior for lung function. Thus, in patients taking FP/SM or FP, montelukast conferred complimentary effects on surrogate inflammatory markers, which were dissociated from lung function. Further studies are required to evaluate whether these effects of montelukast translate into clinical benefits.
authors.affiliation: Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Currie
authors.forename: Daniel K C
authors.initials: DK
authors.lastname: Lee
authors.forename: Kay
authors.initials: K
authors.lastname: Haggart
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Bates
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000085:Acetates / Q000276:immunology / Q000627:therapeutic use*; D000249:Adenosine Monophosphate; D000293:Adolescent; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use*; D000730:Androstadienes / Q000276:immunology / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000276:immunology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D001985:Bronchial Provocation Tests; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D020024:Leukotriene Antagonists / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000276:immunology / Q000627:therapeutic use*; D000068299:Salmeterol Xinafoate; D012720:Severity of Illness Index; D013440:Sulfides; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D000249:Adenosine Monophosphate; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; C093875:montelukast; D000420:Albuterol