Identification of molecular subphenotypes in two cohorts of paediatric ARDS

Nadir Yehya, Matt S. Zinter, Jill M. Thompson, Michelle J. Lim, Mark R. Hanudel, Mustafa F. Alkhouli, Hector Wong, Matthew N. Alder, Daniel J. McKeone, E. Scott Halstead, Pratik Sinha, Anil Sapru

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish
Pages (from-to)128-134
Number of pages7
Issue number2
StatePublished - Oct 9 2023


  • ARDS
  • critical care
  • paediatric lung disaese


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