Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Division of Emergency Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.
Department of Pediatrics, Northwestern School of Medicine, Division of Emergency Medicine, and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
Ann Emerg Med. 2020 Jun;75(6):744-754. doi: 10.1016/j.annemergmed.2019.09.020. Epub 2020 Jan 23.
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.
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.
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.
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.
脓毒症的识别是儿童临床面临的一项挑战。本研究旨在确定外周血基因表达谱是否与儿童疑似脓毒症的病原体类型和脓毒症严重程度相关。
这是一项在三级儿科急诊中心进行的前瞻性试点观察性研究，采用便利抽样法纳入参与者。参与者年龄大于 56 天且小于 18 岁，患有疑似脓毒症，且在过去 4 小时内未接受广谱抗生素治疗。主要结局是病原体来源，定义为无菌体液中证实的细菌来源或证实的病毒来源。次要结局是脓毒症严重程度，定义为在最初 3 天住院期间逆转休克所需的最大治疗。在脓毒症方案启动时采集外周血进行核糖核酸分离，使用 GeneChip Human Gene 2.0 ST 阵列获得基因表达测量值，并进行差异表达分析。
我们从 122 名疑似脓毒症和 12 名健康对照的便利样本中收集了核糖核酸样本。我们比较了 66 名（54%）确诊细菌或病毒感染的儿童，发现了 558 个差异表达基因，其中许多与干扰素信号或病毒免疫有关。我们没有发现根据脓毒症严重程度，患者的基因表达差异具有统计学意义。
该研究证明了在儿科急诊中心评估脓毒症的儿童中评估基因表达谱数据的可行性。我们的结果表明，基因表达谱分析可能有助于确定疑似脓毒症儿童的病原体来源，这最终可能导致脓毒症治疗和抗菌药物管理的个体化治疗得到改善。
