Oxidative stress in acute respiratory distress syndrome (ARDS) is considered as an important pathophysiological mechanism in acute impairment of lung function. The present study investigated whether a pulmonary oxidant±antioxidant imbalance is indicated by substantial oxidative modification of proteins in bronchoalveolar lavage (BAL) fluid.Oxidatively modified proteins in BAL fluid, as measured by the reduction of protein carbonyl groups with tritiated borohydride, were studied in control subjects, patients with clinically established ARDS, and patients considered at-risk for ARDS because they had had coronary bypass surgery. Subsets of these at-risk patients were pretreated either with methylprednisolone or N-acetylcysteine.The carbonyl content of BAL fluid proteins was greatly increased in ARDS patients (5.0 1.3 nmol carbonyl . mL -1 BAL fluid; mean SEM; p=0.0004; n=10) and moderately increased in the untreated patients at-risk for ARDS (1.3 0.2 nmol . mL -1 ; p=0.027; n=19) compared with controls (0.8 0.2 nmol . mL -1 ; n=12). The two other at-risk groups pretreated either with methylprednisolone or N-acetylcysteine showed carbonyl values that were statistically not different from the controls (1.2 0.2 nmol . mL -1 ; p=0.13; n=13, and 1.1 0.3 nmol . mL -1 ; p=0.40; n=8, respectively).These results show that oxidatively modified proteins clearly accumulated in bronchoalveolar lavage fluid of acute respiratory distress syndrome patients, and to a minor extent in untreated at-risk patients. These data suggest a severe oxidant± antioxidant imbalance in acute respiratory distress syndrome. Eur Respir J 1999; 13: 169±174. Many pulmonary diseases, including the acute respiratory distress syndrome (ARDS), chronic bronchitis/emphysema, asthma, and interstitial pulmonary fibrosis [1±3] have been associated with an excess of reactive oxygen species (ROS). Patients undergoing cardiopulmonary bypass (CPB) surgery have an elevated risk of developing ARDS [4] and also appear to be under oxidative stress [5]. In ARDS patients and patients at-risk for ARDS, the epithelial lining fluid (ELF) recovered as bronchoalveolar lavage (BAL) fluid is characterized by increased numbers of neutrophils [6] that are known to be potent in generating superoxide anions. BAL fluid of ARDS patients and at-risk patients contains a variety of cytokines [6,7] as well as lipid mediators [8] that are known to prime or activate neutrophils for oxidant production. Substantial lack of the antioxidant glutathione (GSH) in the respiratory tract of ARDS patients as described by BUNNELL and PACHT [9] may enhance the risk for oxidant injury. The delicate balance between oxidant and antioxidant systems, however, is of major importance for maintaining normal lung function and structure. In the plasma of ARDS patients and patients at-risk for ARDS, oxidative stress was concluded from the formation of lipid peroxidation products [5,10], and protein oxidation [5,11]. However, the situation in plasma does not necessarily reflect the situation in the l...
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