Serial Measurements of Protein Biomarkers in Sepsis-Induced Acute Respiratory Distress Syndrome

• Type of Material: Article
• Authors: Philip Yang, Grady Memorial Hospital Atlanta; Elizabeth Iffrig, Grady Memorial Hospital Atlanta; Frank Harris, Emory University; Andre Holder, Emory University; Gregory Martin, Emory University; Annette Esper, Emory University
• Language: English
• Date: 2022-10-20
• Publisher: Wolters Kluwer Health, Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/CCE.0000000000000780
• Title of Journal or Parent Work: Critical Care Explorations
• Volume: 4
• Issue: 10
• Start Page: E0780
• End Page: E0780
• Grant/Funding Information: Dr. Yang was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under Award Number TL1TR002382/UL1TR002378 (2020–2021) and the National Heart, Lung, and Blood Institute of the NIH under Award Number 5T32HL116271-08 (2021–2022). Dr. Holder is supported by the National Institute of General Medical Sciences of the NIH under Award Number K23GM37182. Dr. Holder reports receiving speaker fees from Baxter International and have received consulting fees from Philips. The remaining authors have no financial disclosures or conflicts of interest to report.
• Keywords: sepsis; acute respiratory distress syndrome; biomarkers
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

IMPORTANCE: The role of early, serial measurements of protein biomarkers in sepsis-induced acute respiratory distress syndrome (ARDS) is not clear. OBJECTIVES: To determine the differences in soluble receptor for advanced glycation end-products (sRAGEs), angiopoietin-2, and surfactant protein-D (SP-D) levels and their changes over time between sepsis patients with and without ARDS. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adult patients admitted to the medical ICU at Grady Memorial Hospital within 72 hours of sepsis diagnosis. MAIN OUTCOMES AND MEASURES: Plasma sRAGE, angiopoietin-2, and SP-D levels were measured for 3 consecutive days after enrollment. The primary outcome was ARDS development, and the secondary outcome of 28-day mortality. The biomarker levels and their changes over time were compared between ARDS and non-ARDS patients and between nonsurvivors and survivors. RESULTS: We enrolled 111 patients, and 21 patients (18.9%) developed ARDS. The three biomarker levels were not significantly different between ARDS and non-ARDS patients on all 3 days of measurement. Nonsurvivors had higher levels of all three biomarkers than did survivors on multiple days. The changes of the biomarker levels over time were not different between the outcome groups. Logistic regression analyses showed association between day 1 SP-D level and mortality (odds ratio, 1.52; 95% CI, 1.03-2.24; p = 0.03), and generalized estimating equation analyses showed association between angiopoietin-2 levels and mortality (estimate 0.0002; se 0.0001; p = 0.04). CONCLUSIONS AND RELEVANCE: Among critically ill patients with sepsis, sRAGE, angiopoietin-2, and SP-D levels were not significantly different between ARDS and non-ARDS patients but were higher in nonsurvivors compared with survivors. The trend toward higher levels of sRAGE and SP-D, but not of angiopoietin-2, in ARDS patients may indicate the importance of epithelial injury in sepsis-induced ARDS. Changes of the biomarker levels over time were not different between the outcome groups.