title: Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate.
abstract: BACKGROUND
  Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved.
  
  
  OBJECTIVE
  We investigated whether or not bronchial responsiveness to leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with asthma.
  
  
  METHODS
  In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD(4) were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an index of cysteinyl-leukotriene biosynthesis.
  
  
  RESULTS
  Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations.
  
  
  CONCLUSIONS
  These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids.
  
  
  CONCLUSIONS
  The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Karolinska University Hospital Solna, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Gyllfors
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Maria
authors.initials: M
authors.lastname: Kumlin
authors.forename: Kjell
authors.initials: K
authors.lastname: Larsson
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006801:Humans; D017998:Leukotriene D4 / Q000494:pharmacology*; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology
chemical_list: D000730:Androstadienes; D016210:Methacholine Chloride; D017998:Leukotriene D4; D017999:Leukotriene E4; D000068298:Fluticasone