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Biological subphenotypes in severe acute hypoxaemic respiratory failure and acute respiratory distress syndrome using rapid prospective classification (SPARC) in the USA: a multicentre, observational, study.

Title: Biological subphenotypes in severe acute hypoxaemic respiratory failure and acute respiratory distress syndrome using rapid prospective classification (SPARC) in the USA: a multicentre, observational, study.
Authors: Files, D Clark1 (AUTHOR) clark.files@wfusm.edu; Matthay, Michael A2 (AUTHOR); Chapple, Andrew G3 (AUTHOR); Barragan, Alejandro Botello3 (AUTHOR); Mabrey, Linzee4 (AUTHOR); Gibbs, Kevin W1 (AUTHOR); Krall, Jennifer1 (AUTHOR); Aggarwal, Neil R5 (AUTHOR); Burnham, Ellen L5 (AUTHOR); Liu, Kathleen D6 (AUTHOR); Meyer, Nuala J7 (AUTHOR); Nates, Joseph L8 (AUTHOR); Youssef, Fady A9 (AUTHOR); Friedman, Eliot10 (AUTHOR); Kett, Daniel H11 (AUTHOR); Koff, Jonathan12 (AUTHOR); Russell, Derek W13 (AUTHOR); Calfee, Carolyn S2 (AUTHOR); Eklund, Martin14 (AUTHOR); Esserman, Laura J15 (AUTHOR)
Source: Lancet Respiratory Medicine. Jul2026, Vol. 14 Issue 7, p601-608. 8p.
Subject Terms: Adult respiratory distress syndrome; Biomarkers; Cohort analysis; Respiratory insufficiency; Classification algorithms; Treatment effectiveness; Artificial respiration; Endotypes
Geographic Terms: United States
Abstract: Two biological subphenotypes in acute respiratory distress syndrome (ARDS) have been identified in retrospective analyses, with differential clinical outcomes and post-hoc responses to investigational treatments. The ability to identify biological subphenotypes in real-time is unknown. We aimed to evaluate the feasibility of using the multisite ISPY COVID Network to prospectively evaluate biological subphenotypes in real-time. This prospective, observational, cohort study enrolled patients with ARDS and severe acute hypoxaemic respiratory failure (AHRF) and assessed the feasibility of real-time stratification into biological subphenotypes using plasma concentrations of IL-6, soluble tumour necrosis factor-1 (TNFR1), and clinical variables. Participants were eligible if they were receiving mechanical ventilation, non-invasive positive pressure ventilation, or heated high flow nasal oxygen (at flow rates ≥30 L/min); had severe AHRF (defined by an SpO 2 to FiO 2 ratio ≤315, calculated with SpO 2 ≤97%, or PaO 2 to FiO 2 ratio
Database: Supplemental Index