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

TitleThe effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease.
Publication TypeJournal Article
Year of Publication2008
AuthorsSin, DD, Man, SFPaul, 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
Corporate AuthorsABC (Advair, Biomarkers in COPD) Investigators
JournalAm J Respir Crit Care Med
Volume177
Issue11
Pagination1207-14
Date Published2008 Jun 1
ISSN1535-4970
KeywordsAdministration, Inhalation, Adrenergic beta-Agonists, Aged, Albuterol, Androstadienes, Anti-Inflammatory Agents, Biological Markers, C-Reactive Protein, Canada, Double-Blind Method, Drug Combinations, Female, Humans, Interleukin-6, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Pulmonary Surfactant-Associated Protein D, Respiratory Function Tests, Treatment Outcome
Abstract

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.

DOI10.1164/rccm.200709-1356OC
Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID18310480