Distinct Blood and Lung Proteins Drive Pulmonary Capillary Leak in Children With Severe Hypoxemic Respiratory Failure
Pediatric Critical Care Medicine, 2026
Gkaifyllia A., Bruzek S., Ignjatovic V., Pober J., Sochet A., Pierce R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Respiratory Diseases | Pathophysiology | Plasma BALF |  Olink Target 48 |
Abstract
Objectives:
Acute hypoxemic respiratory failure is a leading cause of death and disability in critically ill children. Pulmonary capillary barrier dysfunction, in large part, drives severity. We aimed to define how blood and tracheobronchial lavage (TBAL) fluid differentially affect pulmonary capillary barrier function and, as a second exploratory aim, identify protein mediators.
Design:
We performed a secondary analysis in April and May of 2024 of blood and TBAL samples from a previously completed observational cohort study of mechanically ventilated children collected from October 2018 to February 2020.
Setting:
Single PICU.
Subjects:
Stored blood and TBAL samples from 65 children requiring mechanical ventilation collected at 24 and 48–72 hours after intubation.
Interventions:
None.
Measurements and Main Results:
We quantified inflammatory proteins in plasma and TBAL using Olink Target 48 Cytokine multiplex. We assessed changes in barrier function of cultured human pulmonary microvascular endothelial cells (HPMECs) using electrical cell-substrate impedance to measure transendothelial electrical resistance. Plasma samples from critically ill children significantly enhanced HPMEC barrier function and contained lower concentrations of proinflammatory cytokines compared with TBAL. Over time, the effects of plasma on barrier integrity diminished, while TBAL samples significantly improved barrier function and had reduced abundance of several proinflammatory cytokines. Notably, TBAL samples from children with severe lung injury augmented HPMEC barriers more than those from children without lung injury, highlighting distinct compartmental and disease-specific influences on HPMEC barriers.
Conclusions:
These unexpected findings reveal that blood and lung compartments contain differentially abundant proteins that exert distinct and evolving influences on pulmonary endothelial integrity in critically ill children. These results may inform on the timing and compartment-specific assessment of biomarkers, and eventually, delivery of therapies.