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Comparison of 16 Pediatric Acute Respiratory Distress Syndrome-Associated Plasma Biomarkers With Changing Lung Injury
James G Williams1, Rhonda L Jones1, Toni L Yunger1
1Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Insights
Biomarker levels in pediatric acute respiratory distress syndrome (PARDS) change over time and correlate with lung injury severity. Soluble intercellular adhesion molecule-1 (sICAM1) showed the strongest correlation, indicating its biological relevance in PARDS.
Area of Science:
- Critical Care Medicine
- Pediatric Pulmonology
- Biomarker Discovery
Background:
- Pediatric acute respiratory distress syndrome (PARDS) significantly impacts pediatric intensive care unit (PICU) morbidity and mortality.
- Existing plasma biomarkers identify PARDS subgroups but their dynamic changes and correlation with lung injury progression are poorly understood.
Purpose of the Study:
- To investigate the temporal changes of plasma biomarkers during the course of PARDS.
- To assess the correlation between biomarker levels and evolving lung injury.
- To compare biomarker profiles in PARDS patients versus critically ill non-PARDS patients.
Main Methods:
- A prospective observational study was conducted at two quaternary care children's hospitals.
- Plasma samples were collected from intubated PARDS patients and non-PARDS critically ill patients on days 1, 3, 7, and 14.
- Concentrations of 16 plasma biomarkers were measured using a fluorometric bead-based assay.
Main Results:
- On day 1, PARDS patients exhibited elevated levels of several inflammatory markers (e.g., TNF-α, IL-8, IFN-γ) and sICAM1, with reduced MMP-9 compared to non-PARDS subjects.
- Biomarker concentrations on day 1 did not correlate with PARDS severity.
- Changes in 11 of 16 biomarkers, notably sICAM1 (R = 0.69), positively correlated with worsening lung injury over the study period.
Conclusions:
- Soluble intercellular adhesion molecule-1 (sICAM1) demonstrated the strongest positive correlation with lung injury progression, suggesting significant biological relevance in PARDS.
- While initial biomarker levels did not predict severity, their dynamic changes over time reflected evolving lung injury.
- The overlap in biomarker profiles between PARDS and non-PARDS patients underscores the challenge of using plasma biomarkers for precise organ-specific pathology identification in critically ill children.
Objectives:
Pediatric acute respiratory distress syndrome (PARDS) is a source of substantial morbidity and mortality in the PICU, and different plasma biomarkers have identified different PARDS and ARDS subgroups. We have a poor understanding of how these biomarkers change over time and with changing lung injuries. We sought to determine how biomarker levels change over PARDS course, whether they are correlated, and whether they are different in critically ill non-PARDS patients.
Design:
Two-center prospective observational study.
Setting:
Two quaternary care academic children's hospitals.
Patients:
Subjects under 18 years of age admitted to the PICU who were intubated and met the Second Pediatric Acute Lung Injury Consensus Conference-2 PARDS diagnostic criteria and nonintubated critically ill subjects without apparent lung disease.
Interventions:
None.
Measurements And Main Results:
Plasma samples were obtained on study days 1, 3, 7, and 14. The levels of 16 biomarkers were measured using a fluorometric bead-based assay. Compared with non-PARDS subjects, on day 1 PARDS subjects had increased concentrations of tumor necrosis factor-alpha, interleukin (IL)-8, interferon-γ, IL17, granzyme B, soluble intercellular adhesion molecule-1 (sICAM1), surfactant protein D, and IL18 but reduced matrix metalloproteinase 9 (MMP-9) concentrations (all p < 0.05). Day 1 biomarker concentrations and PARDS severity were not correlated. Over PARDS course, changes in 11 of the 16 biomarkers positively correlated with changing lung injury with sICAM1 ( R = 0.69, p = 2.2 × 10 -16 ) having the strongest correlation. By Spearman rank correlation of biomarker concentrations in PARDS subjects, we identified two patterns. One had elevations of plasminogen activator inhibitor-1, MMP-9, and myeloperoxidase, and the other had higher inflammatory cytokines.
Conclusions:
sICAM1 had the strongest positive correlation with worsening lung injury across all study time points suggesting that it is perhaps the most biologically relevant of the 16 analytes. There was no correlation between biomarker concentration on day 1 and day 1 PARDS severity; however, changes in most biomarkers over time positively correlated with changing lung injury. Finally, in day 1 samples, 7 of the 16 biomarkers were not significantly different between PARDS and critically ill non-PARDS subjects. These data highlight the difficulty of using plasma biomarkers to identify organ-specific pathology in critically ill patients.
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