Peripheral blood transcriptomic sub-phenotypes of pediatric acute respiratory distress syndrome

Acute 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.

This 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.

We 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.

We 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.