title: Bronchodilator reversibility, airway eosinophilia and anti-inflammatory effects of inhaled fluticasone in COPD are not related.
abstract: OBJECTIVE
  Bronchodilator reversibility (BDR) is common in smoking-related COPD, but the airway pathology underlying this has not been described. In particular, it is not known whether BDR is associated with underlying airway eosinophilia and whether BDR is predictive of a better response to inhaled corticosteroid (ICS) treatment.
  
  
  METHODS
  A double-blind, placebo-controlled, randomized 2:1 study of fluticasone propionate (FP), 500 microg twice daily versus placebo over 6 months was performed in subjects with mild to moderate COPD. Subjects with a clinical history of asthma were excluded, but not on BDR criteria alone. Induced sputum, BAL and endobronchial biopsies (EBB) were performed in 36 subjects at baseline, and 30 of these provided a second full set of samples (FP, n = 19; placebo, n = 11).
  
  
  RESULTS
  Baseline BDR was not related to airway eosinophilia and did not predict response to ICS. Post-bronchodilator FEV(1) increased in the FP group compared with the placebo group (P = 0.05), and there were within-treatment group reductions in total symptom scores with FP (P < 0.05). Compared with placebo, FP reduced macrophage numbers but increased neutrophil numbers in EBB (P = 0.01 and P = 0.003, respectively). BAL neutrophil and epithelial cell numbers were also reduced with FP (P = 0.03 for both). There were within-treatment group reductions in the numbers of EBB mast cells and CD8+ve lymphocytes with FP (P = 0.007).
  
  
  CONCLUSIONS
  BDR was not related to any particular inflammatory phenotype or any clinical or anti-inflammatory response to ICS in these subjects with mild to moderate COPD.
authors.affiliation: Respiratory Research Group, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Reid
authors.forename: Yudong
authors.initials: Y
authors.lastname: Wen
authors.forename: David P
authors.initials: DP
authors.lastname: Johns
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Williams
authors.forename: Chris
authors.initials: C
authors.lastname: Ward
authors.forename: E Haydn
authors.initials: EH
authors.lastname: Walters
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000730:Androstadienes / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004802:Eosinophilia / Q000188:drug therapy*; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects; D013183:Sputum / Q000166:cytology; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000068298:Fluticasone