Circulating markers of endothelial and alveolar epithelial dysfunction are associated with mortality in pediatric acute respiratory distress syndrome.

Abstract

Angiopoietin 2 (Ang2) and soluble receptor for advanced glycation end products (sRAGE) are markers of endothelial and pulmonary epithelial damage with prognostic implications in adult acute respiratory distress syndrome (ARDS), but unclear significance in pediatric ARDS (PARDS). This was a prospective, observational study in children with PARDS (2012 Berlin and 2015 PALICC definitions) at the Children's Hospital of Philadelphia. Plasma was collected within 48h of PARDS onset and biomarkers quantified by enzyme-linked immunosorbent assay. In 82 children with PARDS (12 deaths, 15%), Ang2 and sRAGE were higher in non-survivors than survivors (p<0.01 for both). Mortality was highest in patients with Ang2 and sRAGE levels both above median values. Ang2 and sRAGE correlated with the number of non-pulmonary organ failures (both p<0.001). Ang2 was higher in indirect lung injury and in immunocompromised children. In stratified analysis, both Ang2 and sRAGE were associated with mortality only in direct lung injury and in immunocompetent children, with no association evident in indirect lung injury or in immunocompromised children. Ang2 and sRAGE in early PARDS were higher in non-survivors than survivors and strongly correlated with number of non-pulmonary organ failures. When stratified by type of lung injury, Ang2 and sRAGE were associated with mortality only in direct lung injury. Similarly, when stratified by immunocompromised status, Ang2 and sRAGE were associated with mortality only in immunocompetent children. The utility of these biomarkers for prognostication and risk stratification requires investigation.