Article Figures & Data
Figures
- Figure 1
Receiver operator characteristic (ROC) curve analysis of the plasma biomarker panels for differentiating ARDS (cases) from controls in patients with severe traumatic injuries in the VALID cohort. The solid line shows predicted probability of occurrence of ARDS for each subject computed from a logistic regression model that included 11 biomarkers (RAGE, PCPIII, BNP, Ang-2, IL-8, TNF-α, IL-10, VWF, SP-D, PAI-1 and CC16). Specificity and sensitivity were computed at each possible cut-off of the predicted probability. The area under the curve (AUC) is 0.78. The dotted line shows the ROC analysis in the same patients using only the two most discriminatory biomarkers (RAGE and Ang-2). The AUC for this model is 0.74. For comparison, the dashed line shows the ROC analysis for clinician recognition of ARDS with an AUC of 0.55. Ang-2, angiopoietin-2; BNP, brain natriuretic peptide; CC16, club cell-16 protein; IL-8, interleukin 8; IL-10; interleukin 10; PAI-1, plasminogen activator inhibitor-1; PCPIII, procollagen peptide-III; RAGE, receptor for advanced glycation endproducts; SP-D, surfactant protein-D; TNF-α, tumor necrosis factor-α; VALID, Validating Acute Lung Injury biomarkers for Diagnosis; VWF, von Willebrand factor antigen.
- Figure 2
The two biomarker (RAGE and Ang-2) multivariable logistic regression model was used to create a prediction model for the probability of ARDS. The value for each predictor variable (RAGE, Ang-2, both in pg/mL) is used to determine a number of points using the point scale at the top. The sum of the individual predictor variable points for the measured RAGE and Ang-2 levels corresponds to the total points and the probability of ARDS shown at the bottom. Ang-2, angiopoietin-2; ARDS, acute respiratory distress syndrome; RAGE, receptor for advanced glycation endproducts.
Tables
- Table 1
Patient characteristics by patient cohort
VALID cohort ACIT cohort Gender study cohort ARDS (n=78) No ARDS (n=315) p ARDS (n=75) No ARDS (n=119) p ARDS (n=105) No ARDS (n=85) p Age (years) 42 (26–55) 41 (27–55) 0.79 41 (27–59) 40 (27–60) 0.93 39 (25–53) 33 (23–47) 0.18 Female 22 (17) 27 (85) 0.35 16 (12) 29 (356) 0.03 34 (36) 29 (25) 0.50 Caucasian 78 (61) 80 (252) 0.94 73 (55) 63 (75) 0.14 83 (87) 84 (71) 0.31 Blunt trauma 86 (67) 84 (263) 0.73 100 (75) 100 (119) NA 85 (88) 86 (72) 0.96 TBI 50 (39) 58 (182) 0.25 75 (56) 71 (84) 0.53 36 (37) 51 (43) 0.036 Arterial base deficit (mEq/L) 8.8±5.0 6.0±5.1 <0.001 6.8±6.5 4.0±4.9 0.007 7.2±5.8 4.6±4.2 <0.001 PaO2/FiO2 143 (103–190) 251 (164–337) <0.001 244 (143–380) 349 (212–454) 0.003 72 (38–140) 123 (89–153) <0.001 ISS 33 (26–38) 26 (18–34) <0.001 30 (26–43) 26 (14–30) <0.001 34 (25–41) 29 (17–35) 0.002 APACHE II 27 (22–31) 22 (18–27) <0.001 16 (12–20) 17 (8–23) 0.84 17 (14–21) 13 (11–17) <0.001 Vent days (to 28 days) 10 (4–15) 4 (2–9) <0.001 11 (7–21) 3 (2–8) <0.001 9 (5–14) 4 (3–7) <0.001 Hospital mortality 10 (8) 9 (29) 0.78 36 (27) 14 (17) <0.001 14 (15) 5 (4) 0.03 Ang-2 (pg/mL) 5880 (4429–7724) 4007 (2763–5816) <0.001 6812 (4323–12223) 4393 (3093–6378) <0.001 8681 (5724–14044) 5697 (3784–8521) <0.001 RAGE (pg/mL) 1886 (956–3298) 944 (646–1523) <0.001 1184 (847–2068) 912 (588–1348) <0.001 2505 (1779–5081) 1415 (1024–2022) <0.001 Data as mean±SD, median (IQR) or percentage (number).
ACIT, Activation of Coagulation and Inflammation in Trauma; Ang-2, angiopoietin-2; APACHE II, Acute Physiology and Chronic Health Evaluation II; FiO2, fractional inspired oxygen; ISS, injury severity score; ARDS, acute respiratory distress syndrome; NA, not available; PaO2, arterial oxygen tension (or pressure); RAGE, receptor for advanced glycation endproducts; TBI, traumatic brain injury, defined as AIS head ≥3; VALID, Validating Acute Lung Injury biomarkers for Diagnosis.
- Table 2
Comparison of 11 plasma biomarkers between ARDS cases and controls in the derivation cohort
Biomarker ARDS (n=79) No ARDS (n=318) p Value RAGE (pg/mL) 1886 (956–3298) 944 (646–1523) <0.001 PCPIII (ng/mL) 3.9 (2.9–5.0) 3.5 (2.7–4.8) 0.251 BNP (ng/mL) 0.4 (0.3–0.7) 0.4 (0.3–0.6) 0.312 Ang-2 (pg/mL) 5880 (4429–7724) 4007 (2763–5816) <0.001 IL-8 (pg/mL) 15.6 (15.6–57.7) 15.6 (15.6–34.9) 0.017 TNF-α (pg/mL) 1.0 (0.6–3.0) 1.4 (0.6–5.1) 0.195 IL-10 (pg/mL) 18.2 (9.4–82.4) 18.1 (8.1–56.7) 0.373 VWF (% control) 230 (173–353) 270 (198–364) 0.045 SP-D (ng/mL) 60.3 (37.2–91.9) 53.6 (32.9–78.4) 0.061 PAI-1 (ng/mL) 118.9 (39.1–248.5) 92.3 (50.6–174.5) 0.476 CC16 (ng/mL) 7.0 (4.2–11.2) 5.5 (3.4–8.6) 0.004 Data as median (IQR).Ang-2, angiopoietin-2; BNP, brain natriuretic peptide; CC16, club cell-16 protein; IL-8, interleukin 8; IL-10; interleukin 10; PAI-1, plasminogen activator inhibitor-1; PCPIII, procollagen peptide-III; RAGE, receptor for advanced glycation endproducts; SP-D, surfactant protein-D; TNF-α, tumor necrosis factor-α; VWF, von Willebrand factor antigen.
- Table 3
Summary of the two-biomarker model for diagnosis of ARDS in the derivation cohort
Biomarker
(upper and lower quartiles)OR for ARDS* 95% CI p RAGE (1846 vs 656) 2.382 1.638 to 3.464 <0.001 Ang-2 (6128 vs 2935) 1.890 1.322 to 2.702 <0.001 *OR for ARDS comparing upper quartile (75th percentile) to lower quartile (25th percentile).
Ang-2, angiopoietin-2; ARDS, acute respiratory distress syndrome; RAGE, receptor for advanced glycation endproducts.
