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Observational Study
. 2024 Jan 18;79(2):128-134.
doi: 10.1136/thorax-2023-220130.

Identification of molecular subphenotypes in two cohorts of paediatric ARDS

Nadir Yehya #  1 , Matt S Zinter #  2   3 , Jill M Thompson  4 , Michelle J Lim  5 , Mark R Hanudel  6 , Mustafa F Alkhouli  2 , Hector Wong  7 , Matthew N Alder  7 , Daniel J McKeone  8 , E Scott Halstead  8 , Pratik Sinha  9   10 , Anil Sapru  6
Affiliations
Observational Study

Identification of molecular subphenotypes in two cohorts of paediatric ARDS

Nadir Yehya et al. Thorax. .

Abstract

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.

Keywords: ARDS; critical care; paediatric lung disaese.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Differences in standardised variables between subphenotypes in the CHOP and UCSF cohorts. Biomarkers were standardised (mean=0, SD=1) and ranked according to degree of separation between subphenotypes. ARDS, acute respiratory distress syndrome; CHOP, Children’s Hospital of Philadelphia; UCSF, University of California San Francisco.
Figure 2
Figure 2
Kaplan-Meier survival curves for the subphenotypes in the CHOP and UCSF cohorts. ARDS, acute respiratory distress syndrome; CHOP, Children’s Hospital of Philadelphia; UCSF, University of California San Francisco.
See this image and copyright information in PMC

References

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