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Plasma Biomarkers for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis*

Terpstra, Matty L. BSc1; Aman, Jurjan MD1; van Nieuw Amerongen, Geerten P. PhD1; Groeneveld, A. B. Johan MD, PhD, FCCP, FCCM2

doi: 10.1097/01.ccm.0000435669.60811.24
Review Articles

Objective: Numerous studies have focused on biomarkers for acute lung injury and acute respiratory distress syndrome. Although several biomarkers have been identified, their relative performance is unclear. We aim to provide a quantitative overview of plasma-derived biomarkers associated with acute respiratory distress syndrome diagnosis or mortality.

Data Sources: MEDLINE (inception to January 2012) and personal databases.

Study Selection: English-language studies on plasma biomarkers associated with acute respiratory distress syndrome diagnosis or mortality.

Data Extraction: Demographic variables, plasma levels of biomarker, statistical data, acute respiratory distress syndrome occurrence, and mortality rates were retrieved. The methodological quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies score. Clinical outcomes included 1) diagnosis of acute respiratory distress syndrome in the at-risk population and 2) mortality in acute respiratory distress syndrome patients. For each biomarker, pooled odds ratios for clinical outcome were calculated by meta-analysis, and biomarkers were ranked according to pooled odds ratio.

Data Synthesis: Fifty-four studies appeared eligible for meta-analysis, together including 3,753 patients. We identified 20 biomarkers for diagnosis of acute respiratory distress syndrome in the at-risk population and 19 biomarkers for mortality of acute respiratory distress syndrome patients. The biomarkers most strongly associated with acute respiratory distress syndrome diagnosis in the at-risk population, when increased, were Krebs von den Lungen-6 (odds ratio [95% CI], 6.1 [3.0–12.1]), lactate dehydrogenase (5.7 [1.7–19.1]), soluble receptor for advanced glycation end products (3.5 [1.7–7.2]), and von Willebrand Factor (3.1 [2.0–5.2]). The biomarkers most strongly associated with acute respiratory distress syndrome mortality, when increased, were interleukin-4 (18.0 [6.0–54.2]), interleukin-2 (11.8 [4.3–32.2]), angiopoietin-2 (6.4 [1.3–30.4]), and Krebs von den Lungen-6 (5.1 [3.0–12.2]). Decreased levels of Protein C were associated with increased odds for acute respiratory distress syndrome diagnosis and mortality.

Conclusions: This meta-analysis provides a unique ranking of plasma biomarkers according to their strength of association with acute respiratory distress syndrome diagnosis or acute respiratory distress syndrome mortality. The relative performance of biomarkers among studies shown in this ranking may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.

1Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.

2Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands.

* See also p. 755.

Ms. Terpstra and Dr. Aman contributed equally to this study.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Drs. Aman (2003T3201) and van Nieuw Amerongen’s (2011T072) institutions received grant support from the Dutch Heart Foundation. Drs. Aman and van Nieuw Amerongen received support for travel from the Dutch Heart Foundation. Dr. van Nieuw Amerongen received support for article research from the Dutch Heart Foundation. Dr. van Nieuw Amerongen is employed by VU University Medical Center. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: j.aman@vumc.nl

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins