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Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, 1635-1639

Effect of High Dose Inhaled Steroid on Cells, Cytokines, and Proteases in Induced Sputum in Chronic Obstructive Pulmonary Disease

SARAH V. CULPITT, WASIM MAZIAK, STELIOS LOUKIDIS, JULIA A. NIGHTINGALE, JOHN L. MATTHEWS, and PETER J. BARNES

Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London; and Respiratory Diseases Unit, Glaxo Wellcome, Stevenage, United Kingdom

Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 µg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.




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Impaired Inhibition by Dexamethasone of Cytokine Release by Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 24 - 31.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
S L Traves, S V Culpitt, R E K Russell, P J Barnes, and L E Donnelly
Increased levels of the chemokines GRO{alpha} and MCP-1 in sputum samples from patients with COPD
Thorax, July 1, 2002; 57(7): 590 - 595.
[Abstract] [Full Text] [PDF]

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Leader of the Working Group: M.M. Kelly, Members of the Working Group:, V. Keatings, R. Leigh, C. Peterson, J. Shute, P. Venge, and R. Djukanovic
Analysis of fluid{-}phase mediators
Eur. Respir. J., July 1, 2002; 20(37_suppl): 24S - 39s.
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 Am. J. Respir. Crit. Care Med.Home page
S. V. Culpitt, C. de Matos, R. E. Russell, L. E. Donnelly, D. F. Rogers, and P. J. Barnes
Effect of Theophylline on Induced Sputum Inflammatory Indices and Neutrophil Chemotaxis in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1371 - 1376.
[Abstract] [Full Text] [PDF]

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 ChestHome page
G. Sturton and M. Fitzgerald
Phosphodiesterase 4 Inhibitors for the Treatment of COPD*
Chest, May 1, 2002; 121 (2009): 192S - 196S.
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W. I. de Boer
Cytokines and Therapy in COPD* : A Promising Combination?
Chest, May 1, 2002; 121 (2009): 209S - 218S.
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P. E. Silkoff, D. Martin, J. Pak, J. Y. Westcott, and R. J. Martin
Exhaled Nitric Oxide Correlated With Induced Sputum Findings in COPD
Chest, April 1, 2001; 119(4): 1049 - 1055.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
C. PILETTE, V. GODDING, R. KISS, M. DELOS, E. VERBEKEN, C. DECAESTECKER, K. DE PAEPE, J.-P. VAERMAN, M. DECRAMER, and Y. SIBILLE
Reduced Epithelial Expression of Secretory Component in Small Airways Correlates with Airflow Obstruction in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., January 1, 2001; 163(1): 185 - 194.
[Abstract] [Full Text]

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 ThoraxHome page
A. Hill, S. Gompertz, and R. Stockley
Factors influencing airway inflammation in chronic obstructive pulmonary disease
Thorax, November 1, 2000; 55(11): 970 - 977.
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P. J. Barnes
Chronic Obstructive Pulmonary Disease
N. Engl. J. Med., July 27, 2000; 343(4): 269 - 280.
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 Am. J. Respir. Crit. Care Med.Home page
P. J. BARNES
Inhaled Corticosteroids Are Not Beneficial in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 342 - 344.
[Full Text]

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 ChestHome page
P. J. Barnes
Mechanisms in COPD : Differences From Asthma
Chest, February 1, 2000; 117 (2009): 10S - 14S.
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