Nitrosative stress, heme oxygenase-1 expression and airway inflammation during severe exacerbations of COPD.

Abstract

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.