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从非靶向代谢组学角度深入了解儿科社区获得性肺炎:一项初步研究。

New insights into pediatric community-acquired pneumonia gained from untargeted metabolomics: A preliminary study.

机构信息

Department of Women's and Children's Health, University of Padova, Padova, Italy.

Institute of Pediatric Research (IRP), Fondazione Città della Speranza, Padova, Italy.

出版信息

Pediatr Pulmonol. 2020 Feb;55(2):418-425. doi: 10.1002/ppul.24602. Epub 2019 Dec 10.

Abstract

BACKGROUND

Available diagnostics often fail to distinguish viral from bacterial causes of pediatric community-acquired pneumonia (pCAP). Metabolomics, which aims at characterizing diseases based on their metabolic signatures, has been applied to expand pathophysiological understanding of many diseases. In this exploratory study, we used the untargeted metabolomic analysis to shed new light on the etiology of pCAP.

METHODS

Liquid chromatography coupled with mass spectrometry was used to quantify the metabolite content of urine samples collected from children hospitalized for CAP of pneumococcal or viral etiology, ascertained using a conservative algorithm combining microbiological and biochemical data.

RESULTS

Fifty-nine children with CAP were enrolled over 16 months. Pneumococcal and viral cases were distinguished by means of a multivariate model based on 93 metabolites, 20 of which were identified and considered as putative biomarkers. Among these, six metabolites belonged to the adrenal steroid synthesis and degradation pathway.

CONCLUSIONS

This preliminary study suggests that viral and pneumococcal pneumonia differently affect the systemic metabolome, with a stronger disruption of the adrenal steroid pathway in pneumococcal pneumonia. This finding may lead to the discovery of novel diagnostic biomarkers and bring us closer to personalized therapy for pCAP.

摘要

背景

现有的诊断方法往往无法区分儿童社区获得性肺炎(pCAP)的病毒和细菌病因。代谢组学旨在根据其代谢特征来描述疾病,已被应用于扩展许多疾病的病理生理学理解。在这项探索性研究中,我们使用非靶向代谢组学分析来揭示 pCAP 的病因。

方法

使用液相色谱-质谱联用技术定量分析了因肺炎链球菌或病毒病因住院的 CAP 患儿的尿液样本中的代谢物含量,该方法使用一种结合了微生物学和生化数据的保守算法来确定病因。

结果

在 16 个月的时间里,共纳入了 59 名患有 CAP 的儿童。通过基于 93 种代谢物的多变量模型区分了肺炎链球菌和病毒性病例,其中 20 种被鉴定为可能的生物标志物。其中,六种代谢物属于肾上腺类固醇合成和降解途径。

结论

这项初步研究表明,病毒性和肺炎链球菌性肺炎会以不同的方式影响全身代谢组,肺炎链球菌性肺炎中肾上腺类固醇途径的破坏更为严重。这一发现可能会导致发现新的诊断生物标志物,并使我们更接近 pCAP 的个体化治疗。

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