The discovery of biological subphenotypes in ARDS: a novel approach to targeted medicine?

Wildi, Karin; Livingstone, Samantha; Palmieri, Chiara; LiBassi, Gianluigi; Suen, Jacky; Fraser, John

doi:10.1186/s40560-021-00528-w

Journal of Intensive Care

Table 1 Characteristics of retrospectively assessed ARDS studies regarding ARDS subphenotypes: study design, analysis method, mortality, reaction to treatment, clinical variables, and biomarkers that differentiated best between subphenotypes of ARDS

From: The discovery of biological subphenotypes in ARDS: a novel approach to targeted medicine?

	Country	Study design and analysis methodAnalysis method	90-day mortality	Evaluation of reaction among P2/P1 to	Clinical variables	Blood parameters
ARMA, n = 473 ALVEOLI, n = 549	USA (NHLBI)	RCT LCA	ARMA P2 44% P1 23% ALVEOLI P2 51% P1 22%	ALVEOLI: application of PEEP	Circulatory: heart rate, BPm, vasoactive use Respiratory: minute ventilation, Pplat, PEEP	Inflammation: IL-6, IL-8, sTNFR-1, CRP, WCC Coagulation: PAI-1, protein C, platelets Endothelial: Ang-2, ICAM-1, vWF Others: bilirubin, bicarbonate, PaCO₂, albumin, glucose
MARS, n = 700	NL	Observational cohort Clustering methods	P2 37.7% P1 21.6%	Macrolide Antibiotics	None	Inflammation: IL-6, IL-8, IL-10, IFN-y Enothelial: Ang-1, Ang-2 Coagulation: PAI-1, antithrombin
FACTT, n = 1000	USA (NHLBI)	RCT LCA	P2 45% P1 22%	Fluid strategy	Circulatory: heart rate, BPs, vasoactive use Respiratory: minute ventilation, airway pressure, PEEP	Inflammation: IL-6, IL-8, TNFR-1, IFN-y Coagulation: PAI-1, protein C, platelets Endothelial: Ang-2, vWF Lung epithelial: RAGE Others: bilirubin, bicarbonate, creatinine, PaCO₂, albumin, glucose, glucose
SAILS, n = 745	USA (NHLBI)	RCT LCA	P2 37.6% P1 21.4%	Rosuvastatin	Circulatory: heart rate, BPs, vasoactive use Respiratory: minute ventilation, respiratory rate, pulmonary risk factors others: urinary output	Inflammation: IL-6, IL-8, sTNFR-1, WCC Coagulation: protein C, platelets, PAI-1, platelets Endothelial: ICAM-1 others: bilirubin, bicarbonate, creatinine, PaCO₂, albumin, glucose
HARP, n = 539	UK/IR	RCT LCA	P2 47% P1 22%	Simvastatin	Circulatory: vasoactive use Pulmonary: PF ratio	Inflammation: IL-6, sTNFR-1 Coagulation: platelets Others: creatinine, bilirubin
Kitsios et al., n = 212	USA (NHLBI)	Observational cohort LCA	ARDS P2 44% P1 22% ARFA P2 53% P1 18%	None	Circulatory: BPs, heart rate Pulmonary: PEEP, Pplat, PF ratio, respiratory rate, PF ratio Others: temperature	Inflammation: IL-6, IL-8, IL-10, TNFR-1, WCC, PCT Coagulation: protein C, platelets Endothelial: ICAM-1, Ang-2 Lung epithelial: RAGE Others: creatinine, PaCO₂, ST-2; fractalkine, pentraxin3, pH art

ARMA Acute Respiratory Management of Acute lung injury, ALVEOLI assessment of low tidal volume and elevated end-expiratory volume to obviate lung injury, MARS Molecular diagnosis and risk stratification of sepsis, FACTT Fluid and Catheter Treatment Trial, SAILS statins for acutely injured lungs from sepsis, HARP hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction, RCT randomized controlled trial, LCA latent cluster analysis, P2 hyperinflammatory subphenotype, P1 hypoinflammatory subpenotype, ARFA at risk for ARDS, BPm mean blood pressure, BPs systolic blood pressure, Pplat plateau pressure, PEEP positive end-exspiratory pressure, IL interleukin, sTNFR-1 soluable tumor necrosis factor receptor-1, CRP C-reactive protein, WCC white cell count, PAI-1 plasminogen inhibitor-1, Ang-1/-2 angiopoetin-1/-2, ICAM-1 intracellular adhesion molecule-1, vWF von Willebrand factor, PaCO₂ arterial CO₂ partial pressure, IFN-γ interferon gamma, RAGE receptor for advanced glycation end-products, PF ratio PaO₂/FiO₂ ratio; ST-2 suppression of tumorigenicity, PCT procalcitonin

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ISSN: 2052-0492

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