The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease.
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.
Sin
Don D
DD
Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, Canada.
Man
S F Paul
SF
Marciniuk
Darcy D
DD
Ford
Gordon
G
FitzGerald
Mark
M
Wong
Eric
E
York
Ernest
E
Mainra
Rajesh R
RR
Ramesh
Warren
W
Melenka
Lyle S
LS
Wilde
Eric
E
Cowie
Robert L
RL
Williams
Dave
D
Gan
Wen Q
WQ
Rousseau
Roxanne
R
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
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