Acute respiratory distress syndrome is characterized clinically by markedly impaired gas exchange and pathologically by exudation of protein rich fluid into the airspaces and inflammatory pulmonary changes including loss of functional surfactant. Clinical trials of exogenous surfactant treatment of adult patients with ARDS have been disappointing, perhaps in part due to the fact that artificial surfactant is rapidly disabled by alveolar macrophage and neutrophil derived proteases and oxidants in the alveolar spaces. The PI and his colleagues propose Phase I and Phase II studies to assess the capacity of selected inhibitors of leukocyte proteases and oxidants to inhibit mediators of inflammatory response. Experimental therapeutic formulations containing these inhibitors will be developed and tested. The inhibitors to be tested will be selected based upon their efficacy in Phase I studies. Inhibitors will be mixed with Surfaxin (a mixture of artificial surfactant phospholipids and a mimic surfactant protein B) to treat the lungs of rabbits with pulmonary inflammatory injury. Additional work will be performed to establish manufacturability and commercial viability of advanced treatments for ARDS. All of these data will prepare for a clinical trial in which Surfaxin is combined with appropriate inhibitors of inflammation for use in patients with acute lung injury.
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