Nitrosative stress, heme oxygenase-1 expression and airway inflammation during severe exacerbations of COPD.
OBJECTIVE
The aim of this study was to examine the relationship between airway inflammation, nitrosative stress, heme-oxygenase expression, and acute severe exacerbations of COPD.


METHODS
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.
Tsoumakidou
Maria
M
Department of Thoracic Medicine, University of Crete, Medical School, PO Box 1352, 71110 Heraklion, Crete, Greece.
Tzanakis
Nikolaos
N
Chrysofakis
Georgios
G
Siafakas
Nikolaos M
NM
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001991:Bronchitis / Q000503:physiopathology; D015331:Cohort Studies; D018450:Disease Progression; D047150:Eosinophil Cationic Protein / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000201:enzymology*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013183:Sputum; D018709:Statistics, Nonparametric
D015415:Biomarkers; D008565:Membrane Proteins; D009195:Peroxidase; D019001:Nitric Oxide Synthase; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D047150:Eosinophil Cationic Protein