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


METHODS
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 48 h of PARDS onset and biomarkers quantified by enzyme-linked immunosorbent assay.


RESULTS
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.


CONCLUSIONS
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.
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Suite 7C-26, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104, USA. yehyan@email.chop.edu.|Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA, 19104, USA. yehyan@email.chop.edu.
Nadir
N
Yehya
Division of Pediatric Critical Care Medicine, Department of Pediatrics and Public Health Science, Penn State Hershey Children's Hospital, 500 University Drive, Hershey, PA, 17033, USA.
Neal J
NJ
Thomas
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA, 19104, USA.
Nuala J
NJ
Meyer
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA, 19104, USA.|Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 717 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104, USA.
Jason D
JD
Christie
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Suite 7C-26, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104, USA.
Robert A
RA
Berg
Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA, 19104, USA.
Susan S
SS
Margulies
D000293:Adolescent; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D055370:Lung Injury / Q000175:diagnosis; D008297:Male; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood*; D012044:Regression Analysis; D012128:Respiratory Distress Syndrome / Q000175:diagnosis*; D012720:Severity of Illness Index
D042702:Angiopoietin-2; D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; C000593871:AGER protein, human
ARDS; Ang2; Angiopoietin 2; PARDS; Soluble receptor for advanced glycation end products; sRAGE