Skip to main content

Table 3 Risk ratios for ARDS development in the at-risk population

From: A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality

  Reference Biomarker role in ARDS Sample size Risk ratio (95% CI) Cut-off Comment
Biomarkers in plasma       
 Adiponectin Palakshappa 2016 [48] Anti-inflammatory 163 1.12 (1.01–1.25) Per 5 mcg/mL  
 Angiopoietin-2 Agrawal 2013 [23] Increased endothelial permeability 167 1.8 (1.0–3.4) Per log10  
 Angiopoietin-2 Fremont 2010 [32] Increased endothelial permeability 192 2.20 (1.19–4.05) Highest vs lowest quartile  
 Angiopoietin-2 Reilly 2018 [49] Increased endothelial permeability 703 1.49 (1.20–1.77) Per log increase  
 Angiopoietin-2 Ware 2017 [54] Increased endothelial permeability 393 1.890 (1.322–2.702) 1st vs 4th quartile  
 Angiopoietin-2 Xu 2018 [55] Increased endothelial permeability 158 1.258 (1.137–1.392)   
 Advanced oxidant protein products Du 2016 [30] Oxidative injury 70 1.164 (1.068–1.269)   
 Brain natriuretic peptide Fremont 2010 [32] Myocardial strain 192 0.45 (0.26–0.77) Highest vs lowest quartile  
 Brain natriuretic peptide Komiya 2011 [40] Myocardial strain 124 14.425 (4.382–47.483) > 500 pg/mL Outcome is CPE
 Club cell secretory protein Jensen 2016 [38] Alveolar epithelial injury 405 2.6 (0.7–9.7) ≥ 42.8 ng/mL Learning cohort
 Club cell secretory protein Jensen 2016 [38] Alveolar epithelial injury 353 0.96 (0.20–4.5) ≥ 42.8 ng/mL Validating cohort
 Club cell secretory protein Lin 2017 [42] Alveolar epithelial injury 212 1.096 (1.085–1.162)   
 C-reactive protein (CRP) Bai 2018 [28] Inflammation 384 1.314 (0.620–1.603)   
 C-reactive protein (CRP) Chen 2019 [29] Inflammation 115 0.994 (0.978–1.010)   
 C-reactive protein (CRP) Huang 2019 [35] Inflammation 152 1.287 (0.295–5.606) ≥ 90.3 mg/L  
 C-reactive protein (CRP) Huang 2019 [36] Inflammation 1933 1.008 (1.007–1.010)   
 C-reactive protein (CRP) Komiya 2011 [40] Inflammation 124 0.106 (0.035–0.323) > 50 mg/L Outcome is CPE
 C-reactive protein (CRP) Lin 2017 [42] Inflammation 212 1.007 (1.001–1.014)   
 C-reactive protein (CRP) Osaka 2011 [47] Inflammation 27 1.029 (0.829–1.293) Per 1 mg/dL increase  
 C-reactive protein (CRP) Wang 2019 [53] Inflammation 109 1.000 (0.992–1.008)   
 C-reactive protein (CRP) Ying 2019 [57] Inflammation 145 1.22 (0.95–1.68)   
 Free 2-chlorofatty acid Meyer 2017 [45] Oxidative injury 198 1.62 (1.25–2.09) Per log10  
 Total 2-chlorofatty acid Meyer 2017 [45] Oxidative injury 198 1.82 (1.32–2.52) Per log10  
 Free 2-chlorostearic acid Meyer 2017 [45] Oxidative injury 198 1.82 (1.41–2.37) Per log10  
 Total 2-chlorostearic acid Meyer 2017 [45] Oxidative injury 198 1.78 (1.31–2.43) Per log10  
 Endocan Gaudet 2018 [33] Leukocyte adhesion inhibition 72 0.001 (0–0.215) > 5.36 ng/mL  
 Endocan Mikkelsen 2012 [46] Leukocyte adhesion inhibition 48 0.69 (0.49–0.97) 1 unit increase  
 Endocan Ying 2019 [57] Leukocyte adhesion modulation 145 1.57 (1.14–2.25)   
 Fibrinogen Luo 2017 [44] Coagulation 157 1.893 (1.141–3.142)   
 Glutamate Bai 2017 [27] Non-essential amino acid, neurotransmitter 50 2.229 (1.082–2.634)   
 Glutamate Bai 2017 [27] Non-essential amino acid, neurotransmitter 42 0.996 (0.965–1.028)   
 Glutamate Bai 2018 [28] Non-essential amino acid 384 3.022 (2.001–4.043)   
 Growth arrest-specific gene 6 Yeh 2017 [56] Endothelial activation 129 1.6 (1.3–2.6)   
 Insulin-like growth factor 1 Ahasic 2012 [24] Pro-fibrotic 531 0.58 (0.42–0.79) Per log10  
 IGF binding protein 3 Ahasic 2012 [24] Pro-fibrotic 531 0.57 (0.40–0.81) Per log10  
 Interleukin-1 beta Aisiku 2016 [25] Pro-inflammatory 194 0.98 (0.73–1.32)   
 Interleukin-1 beta Chen 2019 [29] Pro-inflammatory 115 1.001 (0.945–1.061)   
 Interleukin-1 beta Huang 2019 [35] Pro-inflammatory 152 0.666 (0.152–2.910) ≥ 11.3 pg/mL  
 Interleukin-1 beta Wang 2019 [53] Pro-inflammatory 109 1.021 (0.982–1.063)   
 Interleukin-6 Aisiku 2016 [25] Pro-inflammatory 195 1.24 (1.05–1.49)   
 Interleukin-6 Bai 2018 [28] Pro-inflammatory 384 1.194 (0.806–1.364)   
 Interleukin-6 Chen 2019 [29] Pro-inflammatory 115 0.998 (0.993–1.003)   
 Interleukin-6 Huang 2019 [35] Pro-inflammatory 152 0.512 (0.156–1.678) ≥ 63.7 pg/mL  
 Interleukin-6 Yeh 2017 [56] Pro-inflammatory 129 1.4 (0.98–1.7)   
 Interleukin-8 Agrawal 2013 [23] Pro-inflammatory 167 1.3 (0.97–1.8) Per log10  
 Interleukin-8 Aisiku 2016 [25] Pro-inflammatory 194 1.26 (1.04–1.53)   
 Interleukin-8 Chen 2019 [29] Pro-inflammatory 115 1.000 (0.996–1.003)   
 Interleukin-8 Fremont 2010 [32] Pro-inflammatory 192 1.81 (1.03–3.17) Highest vs lowest quartile  
 Interleukin-8 Liu 2017 [43] Pro-inflammatory 134 1.4 (0.98–1.7) Per log10  
 Interleukin-8 Yeh 2017 [56] Pro-inflammatory 129 1.4 (0.92–1.7)   
 Interleukin-10 Aisiku 2016 [25] Anti-inflammatory 195 1.66 (1.22–2.26)   
 Interleukin-10 Chen 2019 [29] Anti-inflammatory 115 1.003 (0.998–1.018)   
 Interleukin-10 Fremont 2010 [32] Anti-inflammatory 192 2.02 (0.96–4.25) Highest vs lowest quartile  
 Interleukin-12p70 Aisiku 2016 [25] Pro-inflammatory 194 1.18 (0.82–1.69)   
 Interleukin-17 Chen 2019 [29] Pro-inflammatory 115 1.003 (1.000–1.007)   Not significant
 Interleukin-17 Huang 2019 [35] Pro-inflammatory 152 0.644 (0.173–2.405) ≥ 144.55 pg/mL  
 Interleukin-17 Wang 2019 [53] Pro-inflammatory 109 1.001 (0.997–1.004)   
 Leukotriene B4 Amat 2000 [26] Pro-inflammatory 35 14.3 (2.3–88.8) > 14 pmol/mL  
 Microparticles Shaver 2017 [51] Coagulation 280 0.693 (0.490–0.980) Per 10 μM  
 Mitochondrial DNA Faust 2020 [31] Damage-associated molecular pattern 224 1.58 (1.14–2.19)   48 h plasma
 Mitochondrial DNA Faust 2020 [31] Damage-associated molecular pattern 120 1.52 (1.12–2.06) Per log copies per microlitre 48 h plasma
 Myeloperoxidase Meyer 2017 [45] Pro-inflammatory 198 1.28 (0.89–1.84) Per log10  
 Nitric oxide Aisiku 2016 [25] Oxidative injury 193 1.60 (0.98–2.90)   
 Parkinson disease 7 Liu 2017 [43] Anti-oxidative injury 134 1.8 (1.1–3.5) Per log10  
 Pre B cell colony enhancing factor Lee 2011 [41] Pro-inflammatory 113 0.78 (0.43–1.41) Per 10 fold increase  
 Procalcitonin Bai 2018 [28] Inflammation 384 1.156 (0.844–1.133)   
 Procalcitonin Chen 2019 [29] Inflammation 115 1.020 (0.966–1.077)   
 Procalcitonin Huang 2019 [35] Inflammation 152 2.506 (0.705–8.913) ≥ 13.2 ng/mL  
 Procalcitonin Huang 2019 [36] Inflammation 1933 1.008 (1.000–1.016)   Not significant
 Procalcitonin Wang 2019 [53] Inflammation 109 1.019 (0.981–1.058)   
 Procollagen III Fremont 2010 [32] Pro-fibrotic 192 2.90 (1.61–5.23) Highest vs lowest quartile  
 Receptor for advanced glycation end products Fremont 2010 [32] Alveolar epithelial injury 192 3.33 (1.85–5.99) Highest vs lowest quartile  
 Receptor for advanced glycation end products Jabaudon 2018 [37] Alveolar epithelial injury 464 2.25 (1.60–3.16) Per log10 Baseline
 Receptor for advanced glycation end products Jabaudon 2018 [37] Alveolar epithelial injury 464 4.33 (2.85–6.56) Per log10 Day 1
 Receptor for advanced glycation end products Jones 2020 [39] Alveolar epithelial injury 672 1.73 (1.35–2.21)   European ancestry
 Receptor for advanced glycation end products Jones 2020 [39] Alveolar epithelial injury 672 2.05 (1.50–2.83)   African ancestry
 Receptor for advanced glycation end products Jones 2020 [39] Alveolar epithelial injury 843 2.56 (2.14–3.06)   European ancestry
 Receptor for advanced glycation end products Ware 2017 [54] Alveolar epithelial injury 393 2.382 (1.638–3.464) 1st vs 4th quartile  
 Receptor interacting protein kinase-3 Shashaty 2019 [50] Increased endothelial permeability 120 1.30 (1.03–1.63) Per 0.5 SD  
 Receptor interacting protein kinase-3 Shashaty 2019 [50] Increased endothelial permeability 180 1.83 (1.35–2.48) Per 0.5 SD  
 Soluble endothelial selectin Osaka 2011 [47] Pro-inflammatory 27 1.099 (1.012–1.260) Per 1 ng/mL increase  
 Soluble urokinase plasminogen activator receptor Chen 2019 [29] Pro-inflammatory 115 1.131 (1.002–1.277)   
 Surfactant protein D Jensen 2016 [38] Alveolar epithelial injury 405 3.4 (1.0–11.4) ≥ 525.6 ng/mL Learning cohort
 Surfactant protein D Jensen 2016 [38] Alveolar epithelial injury 353 8.4 (2.0–35.4) ≥ 525.6 ng/mL Validating cohort
 Surfactant protein D Suzuki 2017 [52] Alveolar epithelial injury 68 5.31 (1.40–20.15) Per log10  
 Tissue inhibitor of matrix metalloproteinase 3 Hendrickson 2018 [34] Decreases endothelial permeability 182 1.4 (1.0–2.0) 1 SD increase  
 Tumour necrosis factor alpha Aisiku 2016 [25] Pro-inflammatory 195 1.03 (0.71–1.51)   
 Tumour necrosis factor alpha Chen 2019 [29] Pro-inflammatory 115 1.002 (0.996–1.009)   
 Tumour necrosis factor alpha Fremont 2010 [32] Pro-inflammatory 192 0.51 (0.27–0.98) Highest vs lowest quartile  
 Tumour necrosis factor alpha Huang 2019 [35] Pro-inflammatory 152 3.999 (0.921–17.375) ≥ 173.0 pg/mL  
 Tumour necrosis factor alpha Wang 2019 [53] Pro-inflammatory 109 1.000 (0.995–1.005)   
Biomarkers in CSF       
 Interleukin-1 beta Aisiku 2016 [25] Pro-inflammatory 174 1.11 (0.80–1.54)   
 Interleukin-6 Aisiku 2016 [25] Pro-inflammatory 174 1.06 (0.95–1.19)   
 Interleukin-8 Aisiku 2016 [25] Pro-inflammatory 173 1.01 (0.92–1.12)   
 Interleukin-10 Aisiku 2016 [25] Anti-inflammatory 174 1.33 (1.00–1.76)   
 Interleukin-12p70 Aisiku 2016 [25] Pro-inflammatory 173 1.52 (1.04–2.21)   
 Nitric oxide Aisiku 2016 [25] Oxidative injury 172 1.66 (0.70–3.97)   
 Tumour necrosis factor alpha Aisiku 2016 [25] Pro-inflammatory 174 1.43 (0.97–2.14)   
Biomarkers in BALF       
 Soluble trombomodulin Suzuki 2017 [52] Endothelial injury 68 7.48 (1.60–34.98)   
  1. Abbreviations: CPE cardiopulmonary effusion, CSF cerebrospinal fluid, BALF bronchoalveolar lavage fluid, SD standard deviation