• Nadir Yehya, Brian M Varisco, Neal J Thomas, Hector R Wong, Jason D Christie, and Rui Feng.
• Department of Anesthesiology and Critical Care Medicine, 6040A Wood Building, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA. yehyan@email.chop.edu.
• Crit Care. 2020 Dec 7; 24 (1): 681.

BackgroundAcute respiratory distress syndrome (ARDS) is heterogeneous and may be amenable to sub-phenotyping to improve enrichment for trials. We aimed to identify subtypes of pediatric ARDS based on whole blood transcriptomics.MethodsThis was a prospective observational study of children with ARDS at the Children's Hospital of Philadelphia (CHOP) between January 2018 and June 2019. We collected blood within 24 h of ARDS onset, generated expression profiles, and performed k-means clustering to identify sub-phenotypes. We tested the association between sub-phenotypes and PICU mortality and ventilator-free days at 28 days using multivariable logistic and competing risk regression, respectively.ResultsWe enrolled 106 subjects, of whom 96 had usable samples. We identified three sub-phenotypes, dubbed CHOP ARDS Transcriptomic Subtypes (CATS) 1, 2, and 3. CATS-1 subjects (n = 31) demonstrated persistent hypoxemia, had ten subjects (32%) with immunocompromising conditions, and 32% mortality. CATS-2 subjects (n = 29) had more immunocompromising diagnoses (48%), rapidly resolving hypoxemia, and 24% mortality. CATS-3 subjects (n = 36) had the fewest comorbidities and also had rapidly resolving hypoxemia and 8% mortality. The CATS-3 subtype was associated with lower mortality (OR 0.18, 95% CI 0.04-0.86) and higher probability of extubation (subdistribution HR 2.39, 95% CI 1.32-4.32), relative to CATS-1 after adjustment for confounders.ConclusionsWe identified three sub-phenotypes of pediatric ARDS using whole blood transcriptomics. The sub-phenotypes had divergent clinical characteristics and prognoses. Further studies should validate these findings and investigate mechanisms underlying differences between sub-phenotypes.

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