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Pulmonary oxidative stress response in young children with cystic fibrosis
J Hull1, P Vervaart, K Grimwood
1Department of Thoracic Medicine, Royal Children's Hospital, Parkville, Melbourne, Australia.
Insights
Cystic fibrosis patients with lung inflammation show higher oxidative stress markers. This increased oxidative stress is linked to inflammation, not the primary cystic fibrosis defect.
Area of Science:
- Pulmonary Medicine
- Pediatric Respiratory Health
- Oxidative Stress Research
Background:
- Oxidative stress is implicated in cystic fibrosis (CF) lung injury.
- Direct evidence and the impact of inflammation on pulmonary antioxidants in CF are lacking.
- This study investigated oxidative stress and glutathione in infants and children with CF.
Purpose of the Study:
- To assess oxidative stress and glutathione levels in infants and young children with cystic fibrosis.
- To determine the relationship between pulmonary inflammation and oxidative stress in CF.
- To investigate the role of gamma-glutamyl transpeptidase (gamma-GT) in glutathione metabolism in CF airways.
Main Methods:
- Bronchoalveolar lavage (BAL) was performed on 32 infants and children with CF and 7 controls.
- The CF group was categorized into those with (CF-I) and without (CF-NI) pulmonary inflammation based on BAL findings.
- Levels of lipid hydroperoxide, total glutathione, and gamma-GT were measured in BAL fluid.
Main Results:
- Lipid hydroperoxide and gamma-GT concentrations were significantly elevated in the CF-I group compared to controls and the CF-NI group.
- The CF-NI and control groups showed similar levels of lipid hydroperoxide and gamma-GT.
- Glutathione concentration was not significantly lower in the CF-I group, although a trend was observed.
Conclusions:
- Airways in cystic fibrosis patients experience increased oxidative stress, primarily due to pulmonary inflammation.
- The observed increase in gamma-GT suggests a mechanism for extracellular glutathione utilization by airway epithelial cells in CF.
- Oxidative stress in CF airways is a consequence of inflammation, not an intrinsic defect of the disease.
Background:
It has been suggested that oxidative stress contributes to lung injury in cystic fibrosis. There is, however, no direct evidence of increased pulmonary oxidative stress in cystic fibrosis nor of the effects of inflammation on the major pulmonary antioxidant, glutathione. A study was undertaken to measure these parameters in infants and young children in the presence or absence of pulmonary inflammation.
Methods:
Thirty two infants and young children with cystic fibrosis of mean (SD) age 21.4 (15.3) months (range 2-54) and seven non-cystic fibrosis control subjects of mean (SD) age 21.0 (21.2) months (range 2-54) were studied using bronchoalveolar lavage (BAL). On the basis of the BAL findings the cystic fibrosis group was divided into those with (CF-I) and those without pulmonary inflammation (CF-NI). Levels of lipid hydroperoxide, total glutathione, and gamma-glutamyl transpeptidase (gamma-GT) were then measured in the BAL fluid.
Results:
The concentrations of lipid hydroperoxide and gamma-GT in the epithelial lining fluid were significantly increased in the CF-I group compared with the control and CF-NI groups, each of which had similar values for these parameters (ratio of geometric means for CF-I group versus control for lipid hydroperoxide 5.4 (95% confidence interval (CI) 1.8 to 15.8) and for gamma-GT 5.2 (95% CI 1.4 to 19.4)). The glutathione concentration tended to be lower in the CF-I subjects but the difference did not reach statistical significance.
Conclusions:
These results demonstrate that the airways in patients with cystic fibrosis are exposed to increased oxidative stress which appears to be a consequence of pulmonary inflammation rather than part of the primary cystic fibrosis defect. The increase in gamma-GT in the CF-I group suggests a mechanism by which extracellular glutathione could be utilised by airway epithelial cells.