Chronic alcoholism alters systemic and pulmonary glutathione redox status

Rationale: Previous studies have linked the development and severity of acute respiratory distress syndrome with a history of alcohol abuse. In clinical studies, this association has been centered on depletion of pulmonary glutathione and subsequent chronic oxidant stress. Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported. Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history. Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked. Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space. Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population.