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Published ahead of print on January 19, 2006, doi:10.1164/rccm.200508-1321OC
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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 736-743, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200508-1321OC

Original Article

Antiinflammatory Effects of Salmeterol/Fluticasone Propionate in Chronic Obstructive Lung Disease

Neil C. Barnes, Yu-Sheng Qiu, Ian D. Pavord, Debbie Parker, Peter A. Davis, Jie Zhu, Malcolm Johnson, Neil C. Thomson, Peter K. Jeffery on behalf of the SCO30005 Study Group

Department of Respiratory Medicine, London Chest Hospital; Lung Pathology Unit, Imperial College London at the Royal Brompton Hospital, London; Institute for Lung Health, Glenfield Hospital, Leicester; GlaxoSmithKline Research and Development Ltd., Greenford, Middlesex, England; and Department of Respiratory Medicine, University of Glasgow, Glasgow, Scotland, United Kingdom

Correspondence and requests for reprints should be addressed to Professor P.K. Jeffery, F.R.C.Path., Lung Pathology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. E-mail: p.jeffery{at}imperial.ac.uk

Rationale: No currently available treatment is reported to reduce the exaggerated airway wall inflammation of chronic obstructive pulmonary disease.

Objectives: We tested the hypothesis that inhaled combined long-acting beta2-agonist (salmeterol) and corticosteroid (fluticasone propionate) will reduce inflammation.

Methods: Bronchial biopsies and induced sputum were taken from 140 current and former smokers (mean age, 64 yr) with moderate to severe disease, randomized in a 13-wk double-blind study to placebo (n = 73) or salmeterol/fluticasone propionate 50/500 µg (n = 67) twice daily. Biopsies were repeated at 12 wk and sputa at 8 and 13 wk. After adjustment for multiplicity, comparisons between active and placebo were made for median change from baseline in the numbers of biopsy CD8+ and CD68+ cells/mm2 and sputum neutrophils.

Measurements and Main Results: Combination therapy was associated with a reduction in biopsy CD8+ cells of –118 cells/mm2 (95% confidence interval [CI], –209 to –42; p = 0.02), a reduction of 36% over placebo (p = 0.001). CD68+ cells were unaffected by combination treatment. Sputum differential (but not total) neutrophils reduced progressively and, at Week 13, significantly with combination treatment (median treatment difference, 8.5%; 95% CI, 1.75%–15.25%; p = 0.04). The combination also significantly reduced biopsy CD45+ and CD4+ cells and cells expressing genes for tumor necrosis factor-{alpha} and IFN-{gamma} and sputum total eosinophils (all p <= 0.03). These antiinflammatory effects were accompanied by a 173-ml (95% CI, 104–242; p < 0.001) improvement in prebronchodilator FEV1.

Conclusions: The combination of salmeterol and fluticasone propionate has a broad spectrum of antiinflammatory effects in both current and former smokers with chronic obstructive pulmonary disease, which may contribute to clinical efficacy.

Key Words: airway inflammation • biopsy • placebo • sputum




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