title: Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD.
abstract: BACKGROUND
  Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke.
  
  
  METHODS
  Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13).
  
  
  RESULTS
  Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.
  
  
  CONCLUSIONS
  We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden ; MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.
authors.forename: Rosamund E
authors.initials: RE
authors.lastname: Dove
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.
authors.forename: Pheneatia
authors.initials: P
authors.lastname: Leong-Smith
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors.forename: Ester
authors.initials: E
authors.lastname: Roos-Engstrand
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Pourazar
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.
authors.forename: Mittal
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors.forename: Annelie F
authors.initials: AF
authors.lastname: Behndig
authors.affiliation: MRC-PHE Centre for Environment and Health, School of Biomedical Sciences, Kings College London, London, UK.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Mudway
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
keywords: bronchoalveolar lavage; bronchoscopy; oxidative stress; smoking