This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This study proposes to test the following hypotheses: 1) Otherwise healthy individuals with a history of chronic alcohol abuse have altered alveolar-capillary barrier function associated with decreased pulmonary GSH concentrations. 2) A history of chronic alcohol abuse will be associated with more severe defects in alveolar-capillary permeability in critically ill patients with ARDS. 3) GSH deficiency is a cause of abnormal alveolar-capillary barrier function in both individuals with a history of chronic alcohol abuse and ARDS patients with a history of alcohol abuse, and oral GSH replacement therapy will correct the abnormality. If these hypotheses can be confirmed, GSH replacement as prophylaxis against acute lung injury in alcoholic patients at risk, and as therapy for alcoholic patients with ARDS can be tested.
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