Pulmonary oxidative stress response in young children with cystic fibrosis.
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.
Hull
J
J
Department of Thoracic Medicine, Royal Children's Hospital, Parkville, Melbourne, Australia.
Vervaart
P
P
Grimwood
K
K
Phelan
P
P
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000032:analysis; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000378:metabolism; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000032:analysis; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D005723:gamma-Glutamyltransferase / Q000032:analysis
D008054:Lipid Peroxides; D005723:gamma-Glutamyltransferase; D005978:Glutathione