? The acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure characterized by severe lung inflammation, a high mortality and no specific therapy other than a protective ventilatory strategy. Studies of individual biological markers in small single center studies of patients with ARDS have revealed major alterations in the cytokine cascade, the inflammatory cascade and the coagulation cascade both in the lung and systemically in ARDS. Despite the wealth of information gained from these biomarker studies, no single biomarker can unequivocally diagnose ARDS or differentiate survivors from non-survivors. Because of the complexity of ARDS, new approaches and methods are needed that can address the clinical pathophysiology of ARDS at a more comprehensive level. Clinical proteomics is a promising approach that has recently been recommended by the NHLBI as an important future direction in ARDS research. The recognition of unique plasma protein profiles that can diagnose ARDS and predict outcome has the potential to be a powerful tool for clinical use, facilitating application of appropriate therapies and stratification in clinical trials. Furthermore, the analysis of a panel of protein biomarkers in a large population of patients with new statistical algorithms will improve our understanding of the pathogenesis of clinical ARDS. Based on the remarkable progress that we have made in identifying specific biomarkers in large well characterized groups of patients either at risk for or with established ARDS, we hypothesize that panels of new and existing protein biomarkers can be used both to diagnose ARDS in at risk patients and to identify patients with ARDS who are at highest risk of adverse clinical outcomes. To address these hypotheses, we will utilize a multi-disciplinary clinical proteomics approach that draws on our expertise in measurement and interpretation of biological markers, high throughput protein assay design, bioinformatics and biostatistics and cutting edge mass spectroscopy proteomic discovery efforts. This multidisciplinary team approach, combined with proven ongoing access to large clinical trial datasets will be used to target major areas of unmet need in both clinical practice and clinical research in ARDS. ? ?
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