Table. Selected plasma protein biomarkers that have been evaluated in patients at risk of developing and those with ARDS, and their potential applications to enrich future clinical trials.

ARDS: acute respiratory distress syndrome. Ang: angiopoietin. sRAGE: soluble receptor for advanced glycation end-products. IL: interleukin. sTNFr: soluble tumor necrosis factor receptor. TNF: tumor necrosis factor. ICU: intensive care unit. SP-D: surfactant protein D. PEEP: positive end-expiratory pressure. ST: suppression of tumorigenicity. PAI: plasminogen activator inhibitor.

Plasma biomarker(s)	Potential application(s)	Reference(s)
Patients at risk of ARDS
Ang-2	Risk prediction for ARDS development Predictive enrichment for the evaluation of therapies targeting the lung endothelium or epithelium for ARDS prevention Prognostic enrichment for ARDS preventive measures and targeted therapies	(36)
sRAGE		(33)
IL-6, IL-8, IL-10, sTNFr1, ST-2, fractalkine, sRAGE, Ang-2, procalcitonin, pentraxin-3	Identification of phenotypes with distinct outcomes among mechanically ventilated ICU patients with acute respiratory failure Predictive enrichment for the evaluation of therapies targeting specific mechanisms of lung injury for ARDS prevention Prognostic enrichment for ARDS preventive measures and targeted therapies	(59)
sRAGE, Ang-2, IL-8, IL-10, TNF-α, procollagen peptide III, and brain natriuretic peptide	Biomarker panel with value for ARDS diagnosis in ICU patients with severe trauma Predictive and prognostic enrichment for the evaluation of interventions or targeted therapies for trauma-related ARDS	(31)
sRAGE, SP-D, IL-6, IL-8, and club cell secretory protein	Biomarker panel with value for ARDS diagnosis in ICU patients with sepsis Predictive and prognostic enrichment for the evaluation of therapies targeting lung epithelial injury and inflammation for sepsis-related ARDS	(26)
TNF-α, IL-6, IL-8	Preoperative identification of inflammatory phenotypes with distinct risks of developing postoperative pulmonary complications among patients undergoing abdominal surgery Predictive enrichment for the evaluation of therapies targeting inflammation to prevent postoperative ARDS Prognostic enrichment for the evaluation of interventions for postoperative ARDS prevention	(60*)
Patients with ARDS
IL-8, sTNFr, bicarbonate	Identification of hypoinflammatory and hyperinflammatory phenotypes with distinct outcomes and therapeutic responses (such as to PEEP, fluid therapy, and simvastatin) among patients with ARDS Predictive enrichment for the evaluation of therapies targeting inflammatory pathways in ARDS Prognostic enrichment for the evaluation of therapeutic interventions, including targeted therapies, in ARDS	(53**)
IL-8, protein C, bicarbonate		(56)
IL-6, Ang-1/2, PAI-1		(57**)
sRAGE	Identification of radiographic phenotypes of focal and nonfocal ARDS Predictive enrichment for the evaluation of therapies targeting lung epithelial injury and inflammation in ARDS Prognostic enrichment for the evaluation of therapeutic interventions, including epithelial-targeted therapies, in ARDS Monitoring the “biological” response to some interventions in ARDS, such as recruitment maneuvers or ventilation strategies	(28*,29,42*,69*,71,88)