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Nitrosative Stress, Heme Oxygenase-1 Expression and Airway Inflammation During Severe Exacerbations of COPD^*

^* From the Department of Thoracic Medicine, University of Crete, Medical School, Heraklion, Crete, Greece.

Correspondence to: Nikolaos M. Siafakas, MD, PhD, FCCP, Professor of Thoracic Medicine, Dept. of Thoracic Medicine, University of Crete, Medical School, PO Box 1352, 71110 Heraklion, Crete, Greece; e-mail: pneumon{at}med.uoc.gr

Study objectives: The aim of this study was to examine the relationship between airway inflammation, nitrosative stress, heme-oxygenase expression, and acute severe exacerbations of COPD.

Design: We measured heme oxygenase (HO)-1, inducible nitric oxide (NO) synthase expression and nitrotyrosine formation, as well as eosinophilic cationic protein, myeloperoxidase (MPO), interleukin (IL-8), and granulocyte macrophage-colony stimulating factor levels in induced sputum samples from 12 COPD patients (mean ± SD; FEV₁ 40 ± 14% predicted) at the onset of an acute severe exacerbation of COPD requiring hospital admission and 16 weeks after remission.

Results: We demonstrated increased percentages (p = 0.001) and absolute numbers (p = 0.028) of total nitrotyrosine positive (+ve) inflammatory cells (ie, polymorphonuclear cells and macrophages), increased percentages (p = 0.04) and absolute numbers (p = 0.05) of total HO-1 +ve inflammatory cells, and increased MPO (p = 0.005) and IL-8 levels (p = 0.028) during severe exacerbation compared with the stable state.

Conclusions: Our results support the hypothesis of an involvement of inflammatory and nitrosative stress in severe COPD exacerbations. Future therapeutic strategies may aim at regulating inflammation and NO synthesis during COPD exacerbations.

Key Words: chronic bronchitis • emphysema • exacerbation • heme oxygenase • inducible nitric oxide synthase • inflammation • nitrotyrosine • oxidative stress • sputum

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				M. Tsoumakidou, E. Papadopouli, N. Tzanakis, and N. M. Siafakas Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma Chest, May 1, 2006; 129(5): 1194 - 1202. [Abstract] [Full Text] [PDF]

				S. Permutt and D. B. Pearse Blood Carbon Monoxide Will Increase from a Decline in Pulmonary Function Alone Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1231 - 1231. [Full Text] [PDF]

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