Fig. 4.

Prototype injury schema in the anatomic components of the alveolar unit in ARDS. (A) Epithelial-dominant injury: associated with cellular infiltrates and alveolar flooding, prototypically seen in pneumonia-associated ARDS and may be neutrophil driven. (B) Extracellular matrix-dominant injury: associated with persistent inflammatory signaling due to stress to the extracellular matrix, prototypically seen with in ventilator-induced lung injury (VILI). (C) Endothelial-dominant injury: associated with endothelial dysfunction and interstitial edema and proteinaceous exudates leading to increased extravascular lung water; prototypically seen in sepsis-induced ARDS. (D) Coagulopathy-dominant injury: this is associated with intravascular thromboembolic phenomena with extensive microthrombi in the pulmonary microvasculature; prototypically seen in COVID-19-associated ARDS. It is worth emphasizing that these figures represent extreme prototypes of the anatomic injuries and most ARDS cases are combination of the injuries to these sites. IL, interleukin; TNF, tumor necrosis factor receptor; NET, neutrophil extracellular traps; ROS, reactive oxygen species; MPO, myeloperoxidase; sRAGE, soluble receptor for advanced glycation endproduct; CC16, Clara cell 16; SP-D, surfactant protein-D; MMP, matrix metalloproteinases; Ang-2, angiopoeitin-2; VEGF, vascular endothelial growth factor; vWF, von Willebrand factor.