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Published on: August 7, 2017
Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory
John Nguyen1, Jill M Thompson1, Daniel R Balcarcel1
1Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.
Insights
Pediatric acute respiratory distress syndrome (ARDS) is worse in immunocompromised children. This study identified specific biomarkers related to inflammation and endothelial damage in these patients, suggesting potential new treatment targets.
Area of Science:
- Pediatric Critical Care Medicine
- Immunology
- Biochemistry
Background:
- Immunocompromised status, including stem cell transplant recipients, is associated with poorer outcomes in pediatric acute respiratory distress syndrome (ARDS).
- Understanding the biochemical profile of immunocompromised children with ARDS is crucial for identifying potential therapeutic targets.
Purpose of the Study:
- To identify a distinct biomarker profile in immunocompromised children with ARDS, with and without stem cell transplant, independent of illness severity.
- To elucidate molecular mechanisms contributing to the heterogeneity and poor prognosis in this high-risk subgroup.
Main Methods:
- Secondary analysis of a prospective cohort study involving intubated children with Berlin-defined ARDS.
- Biomarker levels were compared between immunocompetent and immunocompromised (with/without stem cell transplant) children.
- Multivariable regression models were used to adjust for illness severity, ARDS etiology, and neutrophil levels to identify independent biomarkers.
Main Results:
- Of 333 children with ARDS, 84 were immunocompromised (39 with stem cell transplant).
- Neutrophil levels correlated with biomarkers; 14 of 18 proteins differed between neutropenic and non-neutropenic patients.
- After multivariable adjustment, 11 biomarkers (e.g., angiopoietin-2, procollagen type III N-terminal peptide) were elevated in immunocompromised subjects without stem cell transplant, indicating endotheliopathy and tissue damage.
- C-C motif chemokine ligand 22 was lower in all immunocompromised subjects.
Conclusions:
- Immunocompromised children with ARDS exhibit elevated pro-inflammatory and endothelial damage biomarkers.
- These findings offer insights into the molecular heterogeneity of ARDS in this population.
- The identified biomarkers may represent targetable pathways to reduce mortality risk in immunocompromised children with ARDS.
Abstract:
Immunocompromised status, with and without stem cell transplant, confers a worse prognosis in pediatric acute respiratory distress syndrome. An improved understanding of the biochemical profile of immunocompromised children with acute respiratory distress syndrome would inform whether specific pathways are targetable, or merely bystanders, in order to improve outcomes in this high-risk subgroup.
Objectives:
We aimed to identify a biomarker profile of immunocompromised children, with and without stem cell transplant, independent of illness severity.
Design Settings And Participants:
This was a secondary analysis of a prospective cohort study of intubated children with Berlin-defined acute respiratory distress syndrome with existing biomarker measurements conducted in a large academic PICU between 2014 and 2019.
Main Outcomes And Measures:
Biomarker levels were compared between immunocompetent and immunocompromised children, with and without stem cell transplant, both prior to and after adjusting for severity of illness.
Results:
In 333 children with acute respiratory distress syndrome, 84 were immunocompromised, of whom 39 had a stem cell transplant. Circulating neutrophil levels were strongly correlated with biomarkers, with 14 of 18 measured proteins differentially expressed in patients with versus without neutropenia. In order to identify biomarker levels independent of severity of illness, acute respiratory distress syndrome etiology, and neutrophil levels, we computed predicted (log-transformed) biomarker levels after adjusting for confounders using linear regression and then compared these severity-adjusted levels between immunocompetent and immunocompromised (with and without stem cell transplant) subjects using analyses of variance and post hoc Bonferroni. After multivariable adjustment, 11 biomarkers were higher in immunocompromised subjects without stem cell transplant, relative to immunocompetent, implicating endotheliopathy (angiopoietin-2), tissue damage (procollagen type III N-terminal peptide), and innate immunity. A single biomarker, C-C motif chemokine ligand 22, was lower in immunocompromised subjects with and without stem cell transplant.
Conclusions And Relevance:
Immunocompromised children with acute respiratory distress syndrome were characterized by elevations in pro-inflammatory and endothelial damage biomarkers. Our study provides insight into mechanisms underlying the molecular heterogeneity of this population and potentially identifies targetable pathways to mitigate their increased mortality risk.
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