Publication: Understanding heterogeneity in biologic phenotypes of acute respiratory distress syndrome by leukocyte expression profiles
Issued Date
2019-01-01
Resource Type
ISSN
15354970
1073449X
1073449X
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2-s2.0-85065716353
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Respiratory and Critical Care Medicine. Vol.200, No.1 (2019), 42-50
Suggested Citation
Lieuwe D.J. Bos, Brendon P. Scicluna, David S.Y. Ong, Olaf Cremer, Tom Van Der Poll, Marcus J. Schultz Understanding heterogeneity in biologic phenotypes of acute respiratory distress syndrome by leukocyte expression profiles. American Journal of Respiratory and Critical Care Medicine. Vol.200, No.1 (2019), 42-50. doi:10.1164/rccm.201809-1808OC Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/52263
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Title
Understanding heterogeneity in biologic phenotypes of acute respiratory distress syndrome by leukocyte expression profiles
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Abstract
© 2019 by the American Thoracic Society. Rationale: Two biologic phenotypes of acute respiratory distress syndrome (ARDS) have been identified based on plasma protein markers in four previous studies. Objectives: To determine if blood leukocyte gene expression is different between the "reactive" and "uninflamed" phenotype. Methods: This is a new study adding blood leukocyte transcriptomics and bioinformatics analysis to an existing patient cohort of ARDS in patients with sepsis admitted to two ICUs during a 1.5-year period. Canonical pathway analysis was performed. Measurements and Main Results: A total of 210 patients with sepsis and ARDS were included, of whom 128 had a reactive and 82 an uninflamed phenotype. A total of 3,332/11,443 (29%) transcripts were significantly different between the phenotypes. Canonical pathway analysis showed upregulation of oxidative phosphorylation genes indicative of mitochondrial dysfunction (52% of genes in pathway). The uninflamed phenotype was characterized by upregulation of mitogen-activated protein kinase pathways. Conclusions: A third of genes are differentially expressed between biologic phenotypes of ARDS supporting the observation that the subgroups of ARDS are incomparable in terms of pathophysiology. These data provide additional support for biologic heterogeneity in patients with ARDS and suggests that a personalized approach to intervention focusing on oxidative phosphorylation is pivotal in this condition.