Abstract
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.
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- Armstrong D. S., Grimwood K., Carlin J. B., Carzino R., Olinsky A., Phelan P. D. Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis. Pediatr Pulmonol. 1996 May;21(5):267–275. doi: 10.1002/(SICI)1099-0496(199605)21:5<267::AID-PPUL1>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
- Brown R. K., Wyatt H., Price J. F., Kelly F. J. Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress. Eur Respir J. 1996 Feb;9(2):334–339. doi: 10.1183/09031936.96.09020334. [DOI] [PubMed] [Google Scholar]
- Cantin A. M., North S. L., Hubbard R. C., Crystal R. G. Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol (1985) 1987 Jul;63(1):152–157. doi: 10.1152/jappl.1987.63.1.152. [DOI] [PubMed] [Google Scholar]
- Joyce-Brady M., Takahashi Y., Oakes S. M., Rishi A. K., Levine R. A., Kinlough C. L., Hughey R. P. Synthesis and release of amphipathic gamma-glutamyl transferase by the pulmonary alveolar type 2 cell. Its redistribution throughout the gas exchange portion of the lung indicates a new role for surfactant. J Biol Chem. 1994 May 13;269(19):14219–14226. [PubMed] [Google Scholar]
- Kugelman A., Choy H. A., Liu R., Shi M. M., Gozal E., Forman H. J. gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells. Am J Respir Cell Mol Biol. 1994 Nov;11(5):586–592. doi: 10.1165/ajrcmb.11.5.7946387. [DOI] [PubMed] [Google Scholar]
- Meyer A., Buhl R., Kampf S., Magnussen H. Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals. Am J Respir Crit Care Med. 1995 Sep;152(3):1055–1060. doi: 10.1164/ajrccm.152.3.7663783. [DOI] [PubMed] [Google Scholar]
- Portal B. C., Richard M. J., Faure H. S., Hadjian A. J., Favier A. E. Altered antioxidant status and increased lipid peroxidation in children with cystic fibrosis. Am J Clin Nutr. 1995 Apr;61(4):843–847. doi: 10.1093/ajcn/61.4.843. [DOI] [PubMed] [Google Scholar]
- Rennard S. I., Basset G., Lecossier D., O'Donnell K. M., Pinkston P., Martin P. G., Crystal R. G. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1985) 1986 Feb;60(2):532–538. doi: 10.1152/jappl.1986.60.2.532. [DOI] [PubMed] [Google Scholar]
- Roum J. H., Buhl R., McElvaney N. G., Borok Z., Crystal R. G. Systemic deficiency of glutathione in cystic fibrosis. J Appl Physiol (1985) 1993 Dec;75(6):2419–2424. doi: 10.1152/jappl.1993.75.6.2419. [DOI] [PubMed] [Google Scholar]
- Turrens J. F., Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J. 1980 Nov 1;191(2):421–427. doi: 10.1042/bj1910421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Ruecker A. A., Bertele R., Harms H. K. Calcium metabolism and cystic fibrosis: mitochondrial abnormalities suggest a modification of the mitochondrial membrane. Pediatr Res. 1984 Jul;18(7):594–599. doi: 10.1203/00006450-198407000-00005. [DOI] [PubMed] [Google Scholar]