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

• Published in: Critical care (London, England) Vol. 24; no. 1; pp. 681 - 10
• Main Authors: Yehya, Nadir, Varisco, Brian M., Thomas, Neal J., Wong, Hector R., Christie, Jason D., Feng, Rui
• Format: Journal Article
• Language: English
• Published: London BioMed Central 07.12.2020; BioMed Central Ltd; BMC
• Subjects: Acute respiratory distress syndrome; ARDS; Biomarkers; Children; Confidence intervals; Critical care; Critical Care Medicine; Emergency Medicine; Endotypes; Failure; Gene expression; Genetic aspects; Hypoxemia; Illnesses; Intensive; Medicine; Medicine & Public Health; Mortality; PARDS; Pediatric research; Pediatric respiratory diseases; Pediatrics; Phenotype; Prognosis; Proteins; Respiratory distress syndrome; Sepsis; Sub-phenotypes; Ventilators; United States; United States > US; Endotypes; Children; Gene expression; PARDS; ARDS; Sub-phenotypes
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1466-609X; 1366-609X
• DOI: 10.1186/s13054-020-03410-7

Background 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. Methods 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. Results 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. Conclusions 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.