TY - JOUR
T1 - Endothelial Biomarkers Are Associated With Indirect Lung Injury in Sepsis-Associated Pediatric Acute Respiratory Distress Syndrome
AU - Whitney, Jane E.
AU - Feng, Rui
AU - Koterba, Natalka
AU - Chen, Fang
AU - Bush, Jenny
AU - Graham, Kathryn
AU - Lacey, Simon F.
AU - Melenhorst, Jan Joseph
AU - Parikh, Samir M.
AU - Weiss, Scott L.
AU - Yehya, Nadir
N1 - Publisher Copyright:
© 2020 The Authors. Published by Wolters Kluwer Health, Inc.
PY - 2020/12/4
Y1 - 2020/12/4
N2 - Objectives: Acute respiratory distress syndrome occurring in the setting of direct versus indirect lung injury may reflect different pathobiologies amenable to different treatment strategies. We sought to test whether a panel of plasma biomarkers differed between children with sepsis-associated direct versus indirect acute respiratory distress syndrome. We hypothesized that a biomarker profile indicative of endothelial activation would be associated with indirect acute respiratory distress syndrome. Design: Observational cohort. Setting: Academic PICU. Subjects: Patients less than 18 years old with sepsis-associated direct (pneumonia, n = 52) or indirect (extrapulmonary sepsis, n = 46) acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Of 58 biomarkers examined, 33 differed by acute respiratory distress syndrome subtype. We used classification and regression tree methodology to examine associations between clinical and biochemical markers and acute respiratory distress syndrome subtype. The classification and regression tree model using only clinical variables (age, sex, race, oncologic comorbidity, and Pediatric Risk of Mortality-III score) performed worse than the classification and regression tree model using five clinical variables and 58 biomarkers. The best classification and regression tree model used only four endothelial biomarkers, including elevated angiopoietin-2/angiopoietin-1 ratio, vascular cell-adhesion molecule, and von Willebrand factor, to identify indirect acute respiratory distress syndrome. Test characteristics were 89% (80-97%) sensitivity, 80% (69-92%) specificity, positive predictive value 84% (74-93%), and negative predictive value 86% (76-96%). Conclusions: Indirect lung injury in children with acute respiratory distress syndrome is characterized by a biomarker profile indicative of endothelial activation, excess inflammation, and worse outcomes. A model using four biomarkers has the potential to be useful for more precisely identifying patients with acute respiratory distress syndrome whose pathobiology may respond to endothelial-targeted therapies in future trials.
AB - Objectives: Acute respiratory distress syndrome occurring in the setting of direct versus indirect lung injury may reflect different pathobiologies amenable to different treatment strategies. We sought to test whether a panel of plasma biomarkers differed between children with sepsis-associated direct versus indirect acute respiratory distress syndrome. We hypothesized that a biomarker profile indicative of endothelial activation would be associated with indirect acute respiratory distress syndrome. Design: Observational cohort. Setting: Academic PICU. Subjects: Patients less than 18 years old with sepsis-associated direct (pneumonia, n = 52) or indirect (extrapulmonary sepsis, n = 46) acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Of 58 biomarkers examined, 33 differed by acute respiratory distress syndrome subtype. We used classification and regression tree methodology to examine associations between clinical and biochemical markers and acute respiratory distress syndrome subtype. The classification and regression tree model using only clinical variables (age, sex, race, oncologic comorbidity, and Pediatric Risk of Mortality-III score) performed worse than the classification and regression tree model using five clinical variables and 58 biomarkers. The best classification and regression tree model used only four endothelial biomarkers, including elevated angiopoietin-2/angiopoietin-1 ratio, vascular cell-adhesion molecule, and von Willebrand factor, to identify indirect acute respiratory distress syndrome. Test characteristics were 89% (80-97%) sensitivity, 80% (69-92%) specificity, positive predictive value 84% (74-93%), and negative predictive value 86% (76-96%). Conclusions: Indirect lung injury in children with acute respiratory distress syndrome is characterized by a biomarker profile indicative of endothelial activation, excess inflammation, and worse outcomes. A model using four biomarkers has the potential to be useful for more precisely identifying patients with acute respiratory distress syndrome whose pathobiology may respond to endothelial-targeted therapies in future trials.
KW - acute respiratory distress syndrome
KW - children
KW - endothelium
KW - lung injury
KW - pediatric
KW - sepsis
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U2 - 10.1097/CCE.0000000000000295
DO - 10.1097/CCE.0000000000000295
M3 - Article
C2 - 33299985
AN - SCOPUS:85110314012
SN - 2639-8028
VL - 2
SP - E0295
JO - Critical Care Explorations
JF - Critical Care Explorations
IS - 12
ER -