title: The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD).
  
  
  OBJECTIVE
  To determine the effect of inhaled corticosteroids with or without long-acting beta(2)-adrenergic agonist on systemic biomarkers of inflammation.
  
  
  METHODS
  We conducted a double-blind randomized placebo-controlled trial across 11 centers (n = 289 patients with FEV(1) of 47.8 +/- 16.2% of predicted) to compare the effects of inhaled fluticasone alone or in combination with salmeterol against placebo on circulating biomarkers of systemic inflammation over 4 weeks. The primary endpoint was C-reactive protein (CRP) level. Secondary molecules of interest were IL-6 and surfactant protein D (SP-D).
  
  
  RESULTS
  Neither fluticasone nor the combination of fluticasone/salmeterol had a significant effect on CRP or IL-6 levels. There was, however, a significant reduction in SP-D levels with fluticasone and fluticasone/salmeterol compared with placebo (P = 0.002). Health status also improved significantly in both the fluticasone and fluticasone/salmeterol groups compared with placebo, driven mostly by improvements in the symptom scores. Changes in the circulating SP-D levels were related to changes in health status scores. FEV(1) improved significantly only in the fluticasone/salmeterol group compared with placebo.
  
  
  CONCLUSIONS
  ICS in conjunction with long-acting beta(2)-adrenergic agonist do not reduce CRP or IL-6 levels in serum of patients with COPD over 4 weeks. They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD.
authors.affiliation: Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
authors.forename: Darcy D
authors.initials: DD
authors.lastname: Marciniuk
authors.forename: Gordon
authors.initials: G
authors.lastname: Ford
authors.forename: Mark
authors.initials: M
authors.lastname: FitzGerald
authors.forename: Eric
authors.initials: E
authors.lastname: Wong
authors.forename: Ernest
authors.initials: E
authors.lastname: York
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Mainra
authors.forename: Warren
authors.initials: W
authors.lastname: Ramesh
authors.forename: Lyle S
authors.initials: LS
authors.lastname: Melenka
authors.forename: Eric
authors.initials: E
authors.lastname: Wilde
authors.forename: Robert L
authors.initials: RL
authors.lastname: Cowie
authors.forename: Dave
authors.initials: D
authors.lastname: Williams
authors.forename: Wen Q
authors.initials: WQ
authors.lastname: Gan
authors.forename: Roxanne
authors.initials: R
authors.lastname: Rousseau
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002170:Canada; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D012129:Respiratory Function Tests; D016896:Treatment Outcome
chemical_list: D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D015850:Interleukin-6; D037663:Pulmonary Surfactant-Associated Protein D; D002097:C-Reactive Protein; D000068298:Fluticasone; D000420:Albuterol