CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Oxidative stress and airway inflammation in severe exacerbations of COPD

E M Drost¹, K M Skwarski², J Sauleda³, N Soler⁴, J Roca⁴, A Agusti³, W MacNee^1,2

¹ ELEGI/Colt Laboratory, Centre for Inflammation Research, University of Edinburgh, Medical School, Edinburgh EH8 9AG, UK
² Royal Infirmary Edinburgh, Little France, Edinburgh EH16 4SA, UK
³ Servei de Pneumologia and Unitat d’investigacio, Hospital Universitari son Dureta, Palma de Mallorca, Spain
⁴ Servei de Pneumologia (ICPCT), Hospital Clinic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain

Correspondence to:
Correspondence to:
Dr E M Drost
ELEGI Laboratory, MRC Centre for Inflammation Research, University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, UK; Ellen.Drost{at}ed.ac.uk

Background: A study was undertaken to assess both oxidative stress and inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD) during severe and very severe exacerbations compared with those with stable COPD, healthy smokers, and non-smokers. Two sites within the lungs were compared: the large airways (in sputum) and the peripheral airways (by bronchoalveolar lavage (BAL)).

Methods: BAL fluid cell numbers and levels of tumour necrosis factor (TNF) and interleukin (IL)-8 were measured as markers of airway inflammation and glutathione (GSH) levels as a marker of antioxidant status. Nuclear translocation of the pro-inflammatory transcription factors nuclear factor-B (NF-B) and activator protein 1 (AP-1) were also measured by electromobility shift assay in BAL fluid leucocytes and lung biopsy samples.

Results: Influx of inflammatory cells into the peripheral airways during exacerbations of COPD was confirmed. Increased IL-8 levels were detected in BAL fluid from patients with stable COPD compared with non-smokers and healthy smokers, with no further increase during exacerbations. In contrast, IL-8 levels in the large airways increased during exacerbations. GSH levels were increased in the BAL fluid of smokers (444%) and patients with stable COPD (235%) compared with non-smokers and were reduced during exacerbations (severe 89.2%; very severe 52.3% compared with stable COPD). NF-B DNA binding in BAL leucocytes was decreased in healthy smokers compared with non-smokers (41.3%, n = 9, p<0.001) but did not differ in COPD patients, whereas AP-1 DNA binding was significantly decreased during exacerbations of COPD.

Conclusion: There is evidence of increased oxidative stress in the airways of patients with COPD that is increased further in severe and very severe exacerbations of the disease. This is associated with increased neutrophil influx and IL-8 levels during exacerbations.

Abbreviations: AP-1, activator protein 1; COPD, chronic obstructive pulmonary disease; EMSA, electrophoretic mobility shift assay, -GCS, gamma-glutamylcysteine synthetase; GSH, glutathione; IL, interleukin; NF-B, nuclear factor-B; TNF, tumour necrosis factor

Keywords: chronic obstructive pulmonary disease; nuclear factor-B; interleukin 8; oxidative stress; glutathione; inflammation

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