The overall goal of this competitive renewal SCOR application is to reduce the morbidity and mortality due to that form of acute respiratory failure generally referred to as the adult respiratory distress syndrome (ARDS). This goal will be approached by pursuing a cohesive, interdisciplinary program of investigation focused upon early detection of acute lung injury, definition of the biochemical and cellular mechanisms which induce and modulate the injury and development of methods for intervention. Excellent collaborative arrangements have been established within the existing SCOR among investigators engaged in basic and clinical research. The present proposal builds upon both the relationships established and the observations made within the present SCOR. The critical need for quality control of investigations in both the clinical and basic sciences, and close integration between them, is recognized in the structure of this SCOR. Five Projects and five Core Units are proposed. These will carry out in vitro, animal and human investigations dealing with: 1-Detection of the early biochemical and cellular events among patients at clinical risk of ARDS; 2-Continuation and extention of investigations to define the fundamental biochemical events involved in the genesis and modulation of acute lung injury in patients and animal models; 3-Continuation of investigations regarding the role of cellular elements in acute lung injury, with particular focus upon the use of the isolated perfused lung model to define the morphologic, biochemical and physiologic consequences of discrete agents; 4-Study of the potential contribution of arachidonic acid metabolites to the induction and modulation of lung injury; and 5-Definition of the risk, sensitivity and specificity of technics for the early identification and specific treatment of bacterial, fungal and viral agents which may induce or complicate the course of ARDS. These five Projects will be supported by five Core Units; an Administrative Core which will provide fiscal-administrative support, a Clinical Core responsible for patient identification, monitoring and sample collection-handling; a Biochemical Core which will provide unique analytic services to the Projects; a Pathology Core which will offer necessary morphologic and other services; and a Rhesus Monkey/Experimental Surgery Core which will support investigations of acute lung injury in the primate. All of the Projects/Cores will be led by experienced investigators with established laboratories who have worked together effectively within the existing SCOR program.
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