New insights in ARDS pathogenesis

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in critically ill patients characterized by hypoxemia and non-compliant lung. In this review, we discuss the pathophysiology of ARDS, including the mechanisms involved in the formation of pulmonary edema, the dysregulated inflammatory and immune responses, the activation of procoagulant events, the cellular communication by extracellular vesicles (EVs) between different types of cells and the interaction of the lung with other organs. Activation of inflammation, coagulation, and cell death processes result in the disruption of the alveolar-capillary membrane and the consequent protein-rich edema formation in the alveoli, in which structural and functional alterations of the alveolar epithelium play an essential role. Inflammation and activated endothelial cells trigger coagulation cascades and platelets that generate a procoagulant state in both the airspace and the intravascular compartment with the formation of fibrin in airspaces and thrombi in the microvasculature that aggravate alveolar injury and gas exchange. The crosstalk between epithelial/endothelial cells, platelets, and immune cells is mediated by EVs, whose role in the pathogenesis of ARDS is not known. Finally, the interaction of the lung with other organs has become an important determinant in the development and resolution of ARDS. Understanding the pathophysiological mechanisms involved in ARDS is crucial to developing new therapeutic strategies.