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

Authors :
Nadir Yehya
Brian M. Varisco
Neal J. Thomas
Hector R. Wong
Jason D. Christie
Rui Feng
Source :
Critical Care, Vol 24, Iss 1, Pp 1-10 (2020)
Publication Year :
2020
Publisher :
BMC, 2020.

Abstract

Abstract 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.

Details

Language :
English
ISSN :
13648535
Volume :
24
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Critical Care
Publication Type :
Academic Journal
Accession number :
edsdoj.fe7dba7581624893b93902fd6421f7cf
Document Type :
article
Full Text :
https://doi.org/10.1186/s13054-020-03410-7