PULMONARY DYSFUNCTION IN CYSTIC-FIBROSIS IS ASSOCIATED WITH OXIDATIVESTRESS

The aim of this study was to determine whether a relationship exists b etween the circulating concentration of antioxidants, or markers of ox idative stress, and pulmonary function in cystic fibrosis patients. Pl asma was obtained from 34 patients attending a cystic fibrosis clinic. Oxidative stress was investigated by measuring the concentrations of circulating lipid hydroperoxides and malondialdehyde (lipid peroxidati on) and protein carbonyls (protein oxidation). Antioxidant status war determined from the plasma concentrations of alpha-tocopherol, ascorbi c acid, uric acid and total sulphydryls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid-expirator y flow (FEF25-75) were measured in 25 of the subjects by spirometry, a nd expressed as percentage predicted for normal height, weight and age . Lung function decreased significantly with age and was associated wi th decreased plasma alpha-tocopherol, ascorbic acid and sulphydryl con centrations. The reduction in pulmonary function correlated with eleva ted plasma malondialdehyde, but not with lipid hydroperoxide or protei n carbonyl concentrations. Patients with severe lung dysfunction (FEV1 <50% predicted) had higher plasma concentrations of lipid hydroperoxi des than those with mild-to-moderate lung dysfunction (FEV1 >50% pred) . This study provides evidence that cystic fibrosis patients have inad equate antioxidant defences to cope with the elevated oxidative stress that they regularly experience. We believe that recurring oxidative l ung injury contributes to the decline in pulmonary function in these p atients.