Molecular and cellular bases for the pathogenesis of acute respiratory distress syndrome. Current approaches to pathogenetic therapy

Abstract

This review presents current concepts on the pathogenesis and approaches to pathogenetic therapy of acute respiratory distress syndrome. The authors addressed mechanisms of early neutrophil activation and the contribution of neutrophil extracellular traps to the progression of inflammatory processes. The review focused on the importance of destabilizing endothelial and alveolar epithelial intercellular junctions for initiation of pulmonary edema, as well as on the role of epithelial sodium channels and aquaporins at the stage of alveolar fluid resorption during the proliferative stage of the syndrome. The contribution of lipid anti-inflammatory mediators to the mechanisms of inflammation resolution was emphasized. The article analyzed results of published experimental and clinical studies that stressed the relevance of searching for new strategies of pharmacological interference with major steps in the pathogenesis of this life-threatening condition. The current capabilities of pathogenetic therapy were described that are aimed at reducing the neutrophil-mediated damage of lung tissue, at decreasing the permeability of the air-blood barrier, and at restoring the structural integrity and normal cellular composition of the lung tissue.