Endothelial Biomarkers Are Associated With Indirect Lung Injury in Sepsis-Associated Pediatric Acute Respiratory Distress Syndrome

Overview

Journal Crit Care Explor

Specialty Critical Care

Date 2020 Dec 10

PMID 33299985

Citations 13

Authors

Jane E Whitney

Rui Feng

Natalka Koterba

Fang Chen

Jenny Bush

Kathryn Graham

Simon F Lacey

Jan Joseph Melenhorst

Samir M Parikh

Scott L Weiss

Nadir Yehya

Affiliations

Soon will be listed here.

Abstract

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, = 52) or indirect (extrapulmonary sepsis, = 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.

Citing Articles

Vascular endothelial cell injury: causes, molecular mechanisms, and treatments.

Xia T, Yu J, Du M, Chen X, Wang C, Li R MedComm (2020). 2025; 6(2):e70057.

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Advances and Challenges in Pediatric Sepsis Diagnosis: Integrating Early Warning Scores and Biomarkers for Improved Prognosis.

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By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome.

Zhang Y, Tan J, Zhao Y, Guan L, Li S BMC Pulm Med. 2025; 25(1):3.

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Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.

Jariyasakoolroj T, Chattipakorn S, Chattipakorn N Pediatr Res. 2024; .

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Whitney J, Johnson G, Varisco B, Raby B, Yehya N Pediatr Crit Care Med. 2024; 25(7):599-608.

PMID: 38591949 PMC: 11222043. DOI: 10.1097/PCC.0000000000003512.

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