Endothelial Glycocalyx Degradation Patterns in Sepsis-Associated Pediatric Acute Respiratory Distress Syndrome: A Single Center Retrospective Observational Study.

acute respiratory distress syndrome glycocalyx glycosaminoglycan mechanical ventilation pediatric intensive care pediatrics proteoglycan sepsis

Journal

Journal of intensive care medicine
ISSN: 1525-1489
Titre abrégé: J Intensive Care Med
Pays: United States
ID NLM: 8610344

Informations de publication

Date de publication:
06 Sep 2023
Historique:
medline: 6 9 2023
pubmed: 6 9 2023
entrez: 6 9 2023
Statut: aheadofprint

Résumé

Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of acute respiratory distress syndrome (ARDS). Constituents of the EGCX shed into circulation, glycosaminoglycans and proteoglycans, may serve as biomarkers of endothelial dysfunction. We sought to define the patterns of plasma EGCX degradation products in children with sepsis-associated pediatric ARDS (PARDS), and test their association with clinical outcomes. We retrospectively analyzed a prospective cohort (2018-2020) of children (≥1 month to <18 years of age) receiving invasive mechanical ventilation for acute respiratory failure for ≥72 h. Children with and without sepsis-associated PARDS were selected from the parent cohort and compared. Blood was collected at time of enrollment. Plasma glycosaminoglycan disaccharide class (heparan sulfate, chondroitin sulfate, and hyaluronan) and sulfation subtypes (heparan sulfate and chondroitin sulfate) were quantified using liquid chromatography tandem mass spectrometry. Plasma proteoglycans (syndecan-1) were measured through an immunoassay. Among the 39 mechanically ventilated children (29 with and 10 without sepsis-associated PARDS), sepsis-associated PARDS patients demonstrated higher levels of heparan sulfate (median 639 ng/mL [interquartile range, IQR 421-902] vs 311 [IQR 228-461]) and syndecan-1 (median 146 ng/mL [IQR 32-315] vs 8 [IQR 8-50]), both Children with sepsis-associated PARDS exhibited higher plasma levels of heparan sulfate disaccharides and syndecan-1, suggesting that EGCX degradation biomarkers may provide insights into endothelial dysfunction and PARDS pathobiology.

Sections du résumé

BACKGROUND BACKGROUND
Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of acute respiratory distress syndrome (ARDS). Constituents of the EGCX shed into circulation, glycosaminoglycans and proteoglycans, may serve as biomarkers of endothelial dysfunction. We sought to define the patterns of plasma EGCX degradation products in children with sepsis-associated pediatric ARDS (PARDS), and test their association with clinical outcomes.
METHODS METHODS
We retrospectively analyzed a prospective cohort (2018-2020) of children (≥1 month to <18 years of age) receiving invasive mechanical ventilation for acute respiratory failure for ≥72 h. Children with and without sepsis-associated PARDS were selected from the parent cohort and compared. Blood was collected at time of enrollment. Plasma glycosaminoglycan disaccharide class (heparan sulfate, chondroitin sulfate, and hyaluronan) and sulfation subtypes (heparan sulfate and chondroitin sulfate) were quantified using liquid chromatography tandem mass spectrometry. Plasma proteoglycans (syndecan-1) were measured through an immunoassay.
RESULTS RESULTS
Among the 39 mechanically ventilated children (29 with and 10 without sepsis-associated PARDS), sepsis-associated PARDS patients demonstrated higher levels of heparan sulfate (median 639 ng/mL [interquartile range, IQR 421-902] vs 311 [IQR 228-461]) and syndecan-1 (median 146 ng/mL [IQR 32-315] vs 8 [IQR 8-50]), both
CONCLUSIONS CONCLUSIONS
Children with sepsis-associated PARDS exhibited higher plasma levels of heparan sulfate disaccharides and syndecan-1, suggesting that EGCX degradation biomarkers may provide insights into endothelial dysfunction and PARDS pathobiology.

Identifiants

DOI: 10.1177/08850666231200162 PMID: 37670670
pubmed: 37670670
doi: 10.1177/08850666231200162
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8850666231200162

Subventions

Organisme : NIGMS NIH HHS
ID : K08 GM144788
Pays : United States

Auteurs

Colin J Sallee (CJ)

Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, CA, USA.
ORCID: 0000-0002-2834-2657

Joseph A Hippensteel (JA)

Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Kristen R Miller (KR)

Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.

Kaori Oshima (K)

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.

Andrew T Pham (AT)

Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Robert P Richter (RP)

Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.

John Belperio (J)

Department of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, David Geffen School of Medicine at University of California Los Angeles and Ronald Reagan Medical Center, Los Angeles, CA, USA.

Yamila L Sierra (YL)

Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.

Andreas Schwingshackl (A)

Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, CA, USA.

Peter M Mourani (PM)

Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.

Eric P Schmidt (EP)

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.

Anil Sapru (A)

Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, CA, USA.

Aline B Maddux (AB)

Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.

Classifications MeSH