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. 2016 Feb 1;310(3):L224-31.
doi: 10.1152/ajplung.00336.2015. Epub 2015 Dec 11.

Plasma angiopoietin-2 outperforms other markers of endothelial injury in prognosticating pediatric ARDS mortality

Matt S Zinter  1 , Aaron Spicer  2 , Benjamin O Orwoll  2 , Mustafa Alkhouli  2 , Christopher C Dvorak  3 , Carolyn S Calfee  4 , Michael A Matthay  4 , Anil Sapru  2
Affiliations

Plasma angiopoietin-2 outperforms other markers of endothelial injury in prognosticating pediatric ARDS mortality

Matt S Zinter et al. Am J Physiol Lung Cell Mol Physiol. .

Abstract

Angiopoietin-2 (Ang-2) is a key mediator of pulmonary vascular permeability. This study tested the association between plasma Ang-2 and mortality in pediatric acute respiratory distress syndrome (ARDS), with stratification for prior hematopoietic cellular transplantation (HCT), given the severe, yet poorly understood, ARDS phenotype of this subgroup. We enrolled 259 children <18 years of age with ARDS; 25 had prior HCT. Plasma Ang-2, von Willebrand Factor antigen (vWF), and vascular endothelial growth factor (VEGF) were measured on ARDS days 1 and 3 and correlated with patient outcomes. Day 1 and day 3 Ang-2 levels were associated with mortality independent of age, sex, race, and P/F ratio [odds ratio (OR) 3.7, 95% CI 1.1-11.5, P = 0.027; and OR 10.2, 95% confidence interval (CI) 2.2-46.5, P = 0.003, for each log10 increase in Ang-2]. vWF was associated with mortality (P = 0.027), but VEGF was not. The association between day 1 Ang-2 and mortality was independent of levels of both vWF and VEGF (OR 3.6, 95% CI 1.1-12.1, P = 0.039, for each log10 increase in Ang-2). 45% of the cohort had a rising Ang-2 between ARDS day 1 and 3 (adjusted mortality OR 3.3, 95% CI 1.2-9.2, P = 0.026). HCT patients with a rising Ang-2 had 70% mortality compared with 13% mortality for those without (OR 16.3, 95% CI 1.3-197.8, P = 0.028). Elevated plasma levels of Ang-2 were associated with mortality independent of vWF and VEGF. A rising Ang-2 between days 1 and 3 was strongly associated with mortality, particularly in pediatric HCT patients, suggesting vulnerability to ongoing endothelial damage.

Keywords: acute respiratory distress syndrome; angiopoietin; endothelial injury; hematopoietic stem cell transplant; pediatrics.

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Figures

Fig. 1.
Fig. 1.
Plasma angiopoietin-2 (Ang-2) levels in pediatric acute respiratory distress syndrome (ARDS), stratified by mortality. Boxes represent median with IQR, whiskers extend to upper and lower adjacent values, and dots represent outliers.
Fig. 2.
Fig. 2.
Plasma vWF and VEGF levels in pediatric ARDS, stratified by mortality. Boxes represent median with IQR; whiskers extend to upper and lower adjacent values, and dots represent outliers.
Fig. 3.
Fig. 3.
Pediatric ARDS mortality stratified by HCT status and rising or falling Ang-2.
Fig. 4.
Fig. 4.
Survival estimates for pediatric ARDS patients based on HCT history and Ang-2. Dropout was recorded for ARDS-related mortality, defined as death while intubated or within 24 h of extubation. P < 0.001 for overall difference among four subgroups. P = 0.0164 for difference among only HCT patients with and without rising Ang-2.
See this image and copyright information in PMC

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