Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile
IMPORTANCE:. 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 s...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2023-01-01
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| Series: | Critical Care Explorations |
| Online Access: | http://journals.lww.com/10.1097/CCE.0000000000000844 |
| _version_ | 1797947123931545600 |
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| author | John Nguyen, BS Jill M. Thompson, MS Daniel R. Balcarcel, MD Matthew N. Alder, MD Daniel J. McKeone, MD E. Scott Halstead, MD Courtney M. Rowan, MD Robert B. Lindell, MD Nadir Yehya, MD |
| author_facet | John Nguyen, BS Jill M. Thompson, MS Daniel R. Balcarcel, MD Matthew N. Alder, MD Daniel J. McKeone, MD E. Scott Halstead, MD Courtney M. Rowan, MD Robert B. Lindell, MD Nadir Yehya, MD |
| author_sort | John Nguyen, BS |
| collection | DOAJ |
| description | IMPORTANCE:. 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. |
| first_indexed | 2024-04-10T21:22:50Z |
| format | Article |
| id | doaj.art-73b10d2031fa4412bf544141a9f0c530 |
| institution | Directory Open Access Journal |
| issn | 2639-8028 |
| language | English |
| last_indexed | 2024-04-10T21:22:50Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Critical Care Explorations |
| spelling | doaj.art-73b10d2031fa4412bf544141a9f0c5302023-01-20T02:33:54ZengWolters KluwerCritical Care Explorations2639-80282023-01-0151e084410.1097/CCE.0000000000000844202301000-00013Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory ProfileJohn Nguyen, BS0Jill M. Thompson, MS1Daniel R. Balcarcel, MD2Matthew N. Alder, MD3Daniel J. McKeone, MD4E. Scott Halstead, MD5Courtney M. Rowan, MD6Robert B. Lindell, MD7Nadir Yehya, MD81 Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.1 Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.1 Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.2 Division of Critical Care Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH.3 Division of Pediatric Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.4 Division of Pediatric Critical Care Medicine, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA.5 Division of Critical Care, Department of Pediatrics, Riley Hospital for Children and Indiana University, Indianapolis, IN.1 Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.1 Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.IMPORTANCE:. 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.http://journals.lww.com/10.1097/CCE.0000000000000844 |
| spellingShingle | John Nguyen, BS Jill M. Thompson, MS Daniel R. Balcarcel, MD Matthew N. Alder, MD Daniel J. McKeone, MD E. Scott Halstead, MD Courtney M. Rowan, MD Robert B. Lindell, MD Nadir Yehya, MD Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile Critical Care Explorations |
| title | Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile |
| title_full | Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile |
| title_fullStr | Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile |
| title_full_unstemmed | Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile |
| title_short | Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile |
| title_sort | immunocompromised children with acute respiratory distress syndrome possess a distinct circulating inflammatory profile |
| url | http://journals.lww.com/10.1097/CCE.0000000000000844 |
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