title: Plasma biomarkers for acute respiratory distress syndrome: a systematic review and meta-analysis*.
abstract: 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.
  
  
  METHODS
  MEDLINE (inception to January 2012) and personal databases.
  
  
  METHODS
  English-language studies on plasma biomarkers associated with acute respiratory distress syndrome diagnosis or mortality.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: 1Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands. 2Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Matty L
authors.initials: ML
authors.lastname: Terpstra
authors.forename: Jurjan
authors.initials: J
authors.lastname: Aman
authors.forename: Geerten P
authors.initials: GP
authors.lastname: van Nieuw Amerongen
authors.forename: A B Johan
authors.initials: AB
authors.lastname: Groeneveld
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000401:mortality / Q000503:physiopathology; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016638:Critical Illness; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008297:Male; D011379:Prognosis; D011486:Protein C / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; D007376:Interleukin-2; D007378:Interleukins; D011486:Protein C; D015847:Interleukin-4