title: Montelukast and bronchial inflammation in asthma: a randomised, double-blind placebo-controlled trial.
abstract: BACKGROUND
  Examination of bronchoalveolar lavage, induced sputum, and peripheral blood indicate that cysteinyl leukotriene receptor blockers decrease inflammatory cells in asthma but these do not examine airway tissue per se.
  
  
  OBJECTIVE
  Our objective was to determine the effect of montelukast, a leukotriene receptor antagonist, on airway tissue inflammatory cells by direct bronchoscopic examination of the bronchial mucosa.
  
  
  METHODS
  Adult subjects with mild asthma (pre-bronchodilator FEV(1)> or =70% predicted; PC(20) of < or =4 mg/mL) were given 10mg/day oral montelukast (N=38) or placebo (N=37) for 6 weeks. Bronchial mucosal eosinophils and mast cells were identified and counted.
  
  
  RESULTS
  Change from baseline in numbers of biopsy EG2+ ("activated") eosinophils was the primary endpoint; numbers of total (chromotrope 2R+) eosinophils and (tryptase+) mast cells were secondary. Unexpectedly, there were many patients with zero EG2+ eosinophils at baseline. There was a within-group decrease in EG2+ cells, from 13.54 cells/mm (at baseline) to 0.79 cells/mm at 6 weeks in the montelukast group (LS mean change; 95% confidence interval=-13.59 [-25.45, -1.74]cells/mm; P<0.05), a change not observed in the placebo group (-1.17 [-13.26, 10.91]cells/mm; NS). The zero-inflated Poisson statistical model demonstrated that montelukast significantly reduced post-treatment EG2+ cells by 80% compared with placebo (95% CI [70.6-86.8%]; P<0.0001). The data for total eosinophils showed similar changes. The reduction in mast cell numbers was 12% (95% CI [7.9, 16.0]; P<0.0001).
  
  
  CONCLUSIONS
  Direct examination of airway tissue confirms that montelukast decreases the number of eosinophils and mast cells in asthma.
authors.affiliation: Department of Respiratory Medicine, Royal London Hospital, London, UK.
authors.forename: C F
authors.initials: CF
authors.lastname: Ramsay
authors.forename: P
authors.initials: P
authors.lastname: Sullivan
authors.forename: M
authors.initials: M
authors.lastname: Gizycki
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: A S
authors.initials: AS
authors.lastname: Swern
authors.forename: N C
authors.initials: NC
authors.lastname: Barnes
authors.forename: T F
authors.initials: TF
authors.lastname: Reiss
authors.forename: P K
authors.initials: PK
authors.lastname: Jeffery
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000473:pathology*; D002452:Cell Count; D003521:Cyclopropanes; D004311:Double-Blind Method; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects*; D008875:Middle Aged; D011804:Quinolines / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology*; D013440:Sulfides; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast