The acute respiratory distress syndrome (ARDS) is a devastating process of rapidly progressive and severe respiratory failure. One of the major challenges in ARDS research is understanding why the intense underlying inflammatory and fibroproliferative processes resolve rapidly in the lungs of some patients, yet continue for prolonged periods in patients with persistent ARDS. The ARDSNet consortium of clinical investigators have enrolled over 100 patients with persistent ARDS in a randomized, double-blind, placebo- controlled trial examining the effects of corticosteroids on clinical outcomes. Bronchoalveolar lavage fluid (BALF) and plasma are collected at entry and again after 7 days of treatment with corticosteroid or placebo. The GOALS of this proposal are to measure the concentrations of selected cytokines and certain biological activities in BALF and plasma samples, selected for their relevance to three distinct pathological processes of persistent ARDS: 1) persistent acute inflammation, 2) fibroproliferation, and 3) capillary proliferation (angiogenesis), and to relate these processes to clinical and biochemical measures of lung function and outcome. We propose a hypothesis- driven approach to the analysis of these data that will relate each of these cytokines to specific end-points predicted by their known biological activities in-vitro. Results from this work will provide important new information on predictors of steroid responsiveness, and the molecular mechanisms and pathogenesis of persistent inflammation, fibroproliferation and angiogenesis in persistent ARDS.
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