Development of a biomarker mortality risk model in acute respiratory distress syndrome

• Published in: Critical care (London, England) Vol. 23; no. 1; p. 410
• Main Authors: Bime, Christian, Casanova, Nancy, Oita, Radu C, Ndukum, Juliet, Lynn, Heather, Camp, Sara M, Lussier, Yves, Abraham, Ivo, Carter, Darrick, Miller, Edmund J, Mekontso-Dessap, Armand, Downs, Charles A, Garcia, Joe G N
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.12.2019; BioMed Central; BMC
• Subjects: Adult; Adult respiratory distress syndrome; Algorithms; APACHE; ARDS; Biological markers; Biomarkers; Biomarkers - analysis; Biomarkers - blood; Classification; Clinical trials; Critical care; Cytokines; Cytokines - analysis; Cytokines - blood; EDTA; Female; Humans; Interleukin 1 Receptor Antagonist Protein - analysis; Interleukin 1 Receptor Antagonist Protein - blood; Interleukin-1beta - analysis; Interleukin-1beta - blood; Interleukin-6 - analysis; Interleukin-6 - blood; Interleukin-8 - analysis; Interleukin-8 - blood; Interleukins; Intramolecular Oxidoreductases - analysis; Intramolecular Oxidoreductases - blood; Latent Class Analysis; Logistic Models; Macrophage Migration-Inhibitory Factors - analysis; Macrophage Migration-Inhibitory Factors - blood; Macrophages; Male; Medical prognosis; Medical research; Middle Aged; Mortality; Niacinamide; Nicotinamide Phosphoribosyltransferase - analysis; Nicotinamide Phosphoribosyltransferase - blood; Patients; Peptide Fragments - analysis; Peptide Fragments - blood; Phenotypes; Predictive analytics; Prognosis; Respiratory distress syndrome; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - epidemiology; Respiratory Distress Syndrome - mortality; Risk assessment; Risk Assessment - methods; Risk Assessment - standards; Sepsis; Sphingosine-1-Phosphate Receptors - analysis; Sphingosine-1-Phosphate Receptors - blood; United Kingdom; Vesicular Transport Proteins - analysis; Vesicular Transport Proteins - blood; United Kingdom; Minneapolis Minnesota; United States > US; Biomarkers; Predictive analytics; Mortality; ARDS
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-019-2697-x

There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.