The effects of chronic alcohol abuse on pulmonary glutathione homeostasis

The incidence and severity of the acute respiratory distress syndrome (ARDS ) is increased in critically ill patients with a prior history of chronic a lcohol abuse; however, the specific mechanisms responsible for this associa tion are unknown. Recently, we determined that chronic ethanol ingestion in rats decreased the alveolar epithelial lining fluid (ELF) concentration of the antioxidant glutathione (GSH), which is a characteristic finding in pa tients with ARDS, However, the effects of chronic alcohol abuse on the huma n alveolar epithelium are essentially unknown. Therefore, as a first step w e asked if chronic alcohol abuse, independent of other comorbid conditions, decreases the concentration of GSH in the human lung. We determined that o therwise healthy chronic alcoholics had significantly decreased ELF concent rations of GSH compared with nonalcoholic control subjects (79 mu mol [48 t o 118 mu mol] versus 576 mu mol [493 to 728 mmol], p < 0.001). Furthermore, the percentage of GSH in the oxidized form was higher in the chronic alcoh olics (9.8% [2.2 to 14.8%] versus 2.8% [0.4 to 4.0%] p = 0.05), indicative of increased utilization of GSH. This is the first; report that chronic alc ohol abuse alters GSH homeostasis in the human lung, and suggests a potenti al mechanism by which chronic alcohol abuse predisposes susceptible patient s to develop ARDS.