Cellular mechanisms of acute lung injury: implications for future treatment in the adult respiratory distress syndrome.

Cellular mechanisms of acute lung injury: implications for future treatment in the adult respiratory distress syndrome The adult respiratory distress syndrome is a catastrophic form of lung injury. When originally described by Ashbaugh and his coworkers in 1967 it had an associated mortality approaching 70%.' Over the intervening 20 years progress in developing specific treatment for it has been disappointing; treatment is in the main supportive and mortality remains at 50-70%.2 The syndrome classically arises after a "latent" period of 24-72 hours following one of the varied insults that may provoke it (the most frequent being multiple trauma, septicaemia, and pancreatitis). Despite the multiplicity of initial predisposing causes, the pathological findings, by the time the patients present with lung disease, are remarkably uniform. In addition to the early histological findings of acute lung inflammation, with leakage of fluid and protein into the interstitium and airspaces, there is also evidence of type II epithelial cell and fibroblast proliferation, and even early deposition of "scar tissue" matrix proteins. This common picture suggests that a shared pathological process may operate in the early stages of most cases of adult respiratory distress syndrome regardless of the precipitating cause. Recent advances in cellular and molecular biological techniques are likely to offer new opportunities for fine dissection of the pathogen-esis of adult respiratory distress syndrome in the early stages. This may lead to the identification of more accurate predictors of very high risk for the full blown clinical adult respiratory distress syndrome, and the latent period may also provide a "window of opportunity" whereby specific mechanism based treatments introduced early for patients at very high risk might be expected to attenuate the severity of lung injury or even to abort the full blown syndrome. The present state of knowledge of the early pathogenesis of the adult respiratory distress syndrome points to a complex interplay between humoral mediators released by the initiating condition and the damaging effects of injurious products released from inflammatory cells on the endo-thelial and epithelial cells of pulmonary microvessels. Neutrophils and the adult respiratory distress syndrome The neutrophil is the archetypical acute inflammatory cell. It contains various potentially histotoxic agents (table 1), many of which have been specifically implicated in inflam-matory diseases.3 The neutrophil has been implicated in animal models of acute lung injury induced by circulating endotoxin,4 hyperoxia,5 and microembolisation6; and investigation of bronchoalveolar lavage fluid from patients with the established adult …