The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease

Am J Respir Crit Care Med. 2008 Jun 1;177(11):1207-14. doi: 10.1164/rccm.200709-1356OC. Epub 2008 Feb 28.


Rationale: Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD).

Objectives: 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).

Measurements and main 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.

Trial registration: NCT00120978.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / administration & dosage*
  • Aged
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives*
  • Androstadienes / administration & dosage*
  • Anti-Inflammatory Agents / administration & dosage*
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Canada
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Fluticasone
  • Fluticasone-Salmeterol Drug Combination
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Surfactant-Associated Protein D / metabolism
  • Respiratory Function Tests
  • Treatment Outcome


  • Adrenergic beta-Agonists
  • Androstadienes
  • Anti-Inflammatory Agents
  • Biomarkers
  • Drug Combinations
  • Fluticasone-Salmeterol Drug Combination
  • Interleukin-6
  • Pulmonary Surfactant-Associated Protein D
  • C-Reactive Protein
  • Fluticasone
  • Albuterol

Associated data