Barnes, N., Qiu, Y., Pavord, I., Parker, D., Davis, P., Zhu, L., Johnson, M., Thomson, N. and Jeffery, P. (2006) Antiinflammatory effects of salmeterol/fluticasone propionate in chronic obstructive lung disease. American Journal of Respiratory and Critical Care Medicine, 173(7), pp. 736-743. (doi: 10.1164/rccm.200508-1321OC)
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Publisher's URL: http://dx.doi.org/10.1164/rccm.200508-1321OC
Abstract
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 β2-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-α and IFN-γ 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.Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Thomson, Professor Neil |
Authors: | Barnes, N., Qiu, Y., Pavord, I., Parker, D., Davis, P., Zhu, L., Johnson, M., Thomson, N., and Jeffery, P. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | American Journal of Respiratory and Critical Care Medicine |
Publisher: | American Thoracic Society |
ISSN: | 1073-449X |
ISSN (Online): | 1535-4970 |
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