Identification of molecular subphenotypes in two cohorts of paediatric ARDS.

Autor:	Yehya N; Division of Pediatric Critical Care, Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA yehyan@email.chop.edu., Zinter MS; Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.; Division of Allergy, Immunology, and Bone Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Thompson JM; Division of Pediatric Critical Care, Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA., Lim MJ; Department of Pediatrics, UC Davis, Davis, California, USA., Hanudel MR; Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA., Alkhouli MF; Department of Pediatrics, University of California San Francisco, San Francisco, California, USA., Wong H; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., Alder MN; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA., McKeone DJ; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA., Halstead ES; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA., Sinha P; Division of Clinical and Translational Research, Washington University School of Medicine, St. Louis, MO, USA.; Division of Critical Care, Department of Anesthesia, Washington University, St. Louis, MO, USA., Sapru A; Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA.
Jazyk:	angličtina
Zdroj:	Thorax [Thorax] 2024 Jan 18; Vol. 79 (2), pp. 128-134. Date of Electronic Publication: 2024 Jan 18.
DOI:	10.1136/thorax-2023-220130
Abstrakt:	Background: Two subphenotypes of acute respiratory distress syndrome (ARDS), hypoinflammatory and hyperinflammatory, have been reported in adults and in a single paediatric cohort. The relevance of these subphenotypes in paediatrics requires further investigation. We aimed to identify subphenotypes in two large observational cohorts of paediatric ARDS and assess their congruence with prior descriptions. Methods: We performed latent class analysis (LCA) separately on two cohorts using biomarkers as inputs. Subphenotypes were compared on clinical characteristics and outcomes. Finally, we assessed overlap with adult cohorts using parsimonious classifiers. Findings: In two cohorts from the Children's Hospital of Philadelphia (n=333) and from a multicentre study based at the University of California San Francisco (n=293), LCA identified two subphenotypes defined by differential elevation of biomarkers reflecting inflammation and endotheliopathy. In both cohorts, hyperinflammatory subjects had greater illness severity, more sepsis and higher mortality (41% and 28% in hyperinflammatory vs 11% and 7% in hypoinflammatory). Both cohorts demonstrated overlap with adult subphenotypes when assessed using parsimonious classifiers. Interpretation: We identified hypoinflammatory and hyperinflammatory subphenotypes of paediatric ARDS from two separate cohorts with utility for prognostic and potentially predictive, enrichment. Future paediatric ARDS trials should identify and leverage biomarker-defined subphenotypes in their analysis. Competing Interests: Competing interests: NY reports funding from Pfizer outside of the scope of this manuscript. MSZ received funding from Sobi for advisory board consulting outside the scope of this manuscript. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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