ARDS Subphenotypes: Understanding a Heterogeneous Syndrome

Abstract

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Fig. 1

Pathobiology of the exudative phase of ARDS. The healthy alveolar-capillary unit (left) and the exudative phase of ARDS (right). AECI type I alveolar epithelial cell, AECII type II alveolar epithelial cell, Ang-2 angiopoietin-2, APC activated protein C, CC-16 club cell (formerly Clara cell) secretory protein 16, CCL chemokine (CC motif) ligand, DAMP damage-associated molecular pattern, ENaC epithelial sodium channel, GAG glycosaminoglycan, HMGB1 high-mobility group box 1 protein, KL-6 Krebs von den Lungen 6, LPS lipopolysaccharide, LTB4 leukotriene B4, MMP matrix metalloproteinase, MPO myeloperoxidase, mtDNA mitochondrial DNA, Na⁺/K⁺ ATPase sodium-potassium ATPase pump, NF-κB nuclear factor kappa light-chain enhancer of activated B cells, NET neutrophil extracellular trap, PAMP pathogen-associated molecular pattern, PRR pattern recognition receptor, ROS reactive oxygen species, sICAM soluble intercellular adhesion molecule, SP surfactant protein, sRAGE soluble receptor for advanced glycation end products, TNF tumor necrosis factor, VEGF vascular endothelial growth factor, vWF von Willebrand factor. (Reused from [3] with permission)

Fig. 2

The hypoinflammatory and hyperinflammatory subphenotypes of ARDS are associated with different biomarkers and outcomes. These two distinct subphenotypes have been identified by Calfee et al. in multiple previous ARDS clinical trial cohorts [27, 29, 40, 41]. IL interleukin, bicarb bicarbonate, TNFr1 tumor necrosis factor receptor 1