Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at-risk for ARDS.

Abstract

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+/-13 nmol carbonyl x 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 x mL(-1); p=0.027; n=19) compared with controls (0.8+/-0.2 nmol x 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 x mL(-1); p=0.13; n=13, and 1.1+/-0.3 nmol x 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.