Immunocompromised Children With ARDS Possess a Distinct Circulating Inflammatory Profile

Saturday, January 21, 2023

2:45 PM – 3:45 PM PT

Location: Exhibit Hall - RST 13

Research Presenters(s)

NY

Nadir Yehya, MD, MSCE

Attending Physician
Children's Hospital of Philadelphia
Cherry Hill, NJ, United States

Disclosure information not submitted.

First Author(s)

JN

John Nguyen, BS

Medical student
Drexel University, United States

Disclosure information not submitted.

Co-Author(s)

JT

Jill Thompson, n/a

Scientist
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States

Disclosure information not submitted.
Daniel Balcarcel (he/him/his)

Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania

Disclosure information not submitted.
MA

Matthew Alder, MD, PhD

Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio

Disclosure information not submitted.
DM

Daniel McKeone, MD

Assistant Professor
Pennsylvania State Milton S Hershey Medical Center, United States

Disclosure information not submitted.
E. Scott Halstead, MD, PhD

Associate Professor
Penn State College of Medicine Hershey Children's Hospital
Hershey, United States

Disclosure information not submitted.
CR

Courtney Rowan, MD

Associate Professor
Riley Hospital For Children at Indiana University Health, Indiana, United States

Disclosure information not submitted.

Co-Author(s)

Robert B. Lindell, MD

Department of Anesthesiology and Critical Care Medicine
Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania, United States

Disclosure information not submitted.

INTRODUCTION: Immunocompromised status, with and without stem cell transplant (SCT), confers a worse prognosis in pediatric acute respiratory distress syndrome (ARDS). An improved understanding of the biochemistry of immunocompromised children with ARDS would inform whether specific pathways are targetable, or merely bystanders, in order to improve outcomes in this high-risk subgroup. Therefore, we aimed to identify a biomarker profile of immunocompromised children, with and without SCT, independent of illness severity.

METHODS : We performed a secondary analysis of a prospective cohort of intubated children with Berlin-defined ARDS with existing biomarker measurements from the Children’s Hospital of Philadelphia between 2014 and 2019. In order to identify biomarker levels independent of illness severity, we computed predicted (log-transformed) biomarker levels after adjusting for confounders (age, ARDS etiology, oxygenation index, vasopressor score, and absolute neutrophil count [ANC]) using linear regression, and then compared these severity-adjusted biomarker levels between immunocompetent and immunocompromised (with and without SCT) subjects using analyses of variance and post-hoc Bonferroni.

RESULTS: In 333 children with ARDS, 84 were immunocompromised, of whom 39 had SCT. ANC strongly correlated with biomarkers, with 14 of 18 proteins differentially expressed in patients with versus without neutropenia. After multivariable adjustment, 11 biomarkers were higher in immunocompromised subjects without SCT, relative to immunocompetent, reflecting differences in inflammation (interleukin [IL]-6 and IL-8), endotheliopathy (angiopoietin 2), and tissue damage (type III procollagen peptide). Immunocompromised subjects with SCT had adjusted biomarker levels averaging between immunocompetent subjects and immunocompromised subjects without SCT. A single biomarker, CCL22, was lower in immunocompromised subjects with and without SCT, consistent with dysregulated regulatory T cell activity.

CONCLUSIONS: Immunocompromised children with ARDS were characterized by elevated pro-inflammatory biomarkers and endotheliopathy. Our study provides insight into mechanisms underlying the molecular heterogeneity of pediatric ARDS, and potentially identifies targetable pathways to mitigate their increased mortality risk.