The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease.
Author(s): Sin DD, Man SF, Marciniuk DD, Ford G, FitzGerald M, Wong E, York E, Mainra RR, Ramesh W, Melenka LS, Wilde E, Cowie RL, Williams D, Gan WQ, Rousseau R, ABC (Advair, Biomarkers in COPD) Investigators
Affiliation(s): Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, Canada.
Publication date & source: 2008-06-01, Am J Respir Crit Care Med., 177(11):1207-14. Epub 2008 Feb 28.
Publication type: Multicenter Study; Randomized Controlled Trial
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.