Gene Expression Profiles in Children With Suspected Sepsis - 28/05/20
, Elizabeth R. Alpern, MD, MSCE d, Mengyuan Kan, PhD e, Maya Shumyatcher, BA e, Katie Hayes, BS c, Ebbing Lautenbach, MD, MSCE b, e, Blanca E. Himes, PhD eAbstract |
Study objective |
Sepsis recognition is a clinical challenge in children. We aim to determine whether peripheral blood gene expression profiles are associated with pathogen type and sepsis severity in children with suspected sepsis.
Methods |
This was a prospective pilot observational study in a tertiary pediatric emergency department with a convenience sample of children enrolled. Participants were older than 56 days and younger than 18 years, had suspected sepsis, and had not received broad-spectrum antibiotics in the previous 4 hours. Primary outcome was source pathogen, defined as confirmed bacterial source from sterile body fluid or confirmed viral source. Secondary outcome was sepsis severity, defined as maximum therapy required for shock reversal in the first 3 hospital days. We drew peripheral blood for ribonucleic acid isolation at the sepsis protocol activation, obtained gene expression measures with the GeneChip Human Gene 2.0 ST Array, and conducted differential expression analysis.
Results |
We collected ribonucleic acid samples from a convenience sample of 122 children with suspected sepsis and 12 healthy controls. We compared the 66 children (54%) with confirmed bacterial or viral infection and found 558 differentially expressed genes, many related to interferon signaling or viral immunity. We did not find statistically significant gene expression differences in patients according to sepsis severity.
Conclusion |
The study demonstrates feasibility of evaluating gene expression profiling data in children evaluated for sepsis in the pediatric emergency department setting. Our results suggest that gene expression profiling may facilitate identification of source pathogen in children with suspected sepsis, which could ultimately lead to improved tailoring of sepsis treatment and antimicrobial stewardship.
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| Please see page 745 for the Editor’s Capsule Summary of this article. |
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| Supervising editor: Lise E. Nigrovic, MD, MPH. Specific detailed information about possible conflict of interest for individual editors is available at editors. |
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| Author contributions: FB, ERA, EL, and BEH conceived and designed the study and obtained research funding. FB and KH supervised the conduct of the study and data collection. MK, MS, and BEH provided statistical advice on study design and analyzed the data. FB drafted the article and all authors contributed substantially to its revision. FB takes responsibility for the paper as a whole. |
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| All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. |
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| Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. This study was funded in part by National Institutes of Health grants K23 HD082368, R01 HL133433, and R01 HL141992. |
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| Funders were not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the article. |
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Vol 75 - N° 6
P. 744-754 - juin 2020 Retour au numéro
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