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利用细胞因子聚类分析识别社区获得性肺炎住院患者的炎症模式:一项初步研究。

Using cluster analysis of cytokines to identify patterns of inflammation in hospitalized patients with community-acquired pneumonia: a pilot study.

作者信息

Wiemken Timothy L, Kelley Robert R, Fernandez-Botran Rafael, Mattingly William A, Arnold Forest W, Furmanek Stephen P, Restrepo Marcos I, Chalmers James D, Peyrani Paula, Cavallazzi Rodrigo, Bordon Jose, Aliberti Stefano, Ramirez Julio A

机构信息

University of Louisville Division of Infectious Diseases, Louisville, Kentucky, USA.

University of Louisville Department of Pathology and Laboratory Medicine, Louisville, Kentucky, USA.

出版信息

Univ Louisville J Respir Infect. 2017;1(1):3-11. doi: 10.18297/jri/vol1/iss1/1/. Epub 2017 Jan 30.

Abstract

INTRODUCTION

Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies.

METHODS

Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN), tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations.

RESULTS

A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum.

CONCLUSIONS

Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

摘要

引言

重度社区获得性肺炎(CAP)患者被认为对细菌感染存在过度炎症反应。旨在调节炎症反应的治疗方法大多未取得成功,这可能反映出CAP是一种异质性疾病,无法通过单一的抗炎方法进行调节。我们假设宿主对肺炎的炎症反应可能具有独特的细胞因子模式,可用于个性化治疗。

方法

在此,我们使用细胞因子分层聚类分析来检查13例住院CAP患者的炎症反应模式是否可以确定。这是对社区获得性肺炎炎症研究组(CAPISG)数据库的二次数据分析。入院当天在血浆和痰液中检测以下细胞因子:白细胞介素(IL)-1β、IL-1受体拮抗剂(IL-1ra)、IL-6、CXCL8(IL-8)、IL-10、IL-12p40、IL-17、干扰素(IFN)、肿瘤坏死因子(TNF)α和CXCL10(IP-10)。使用分层凝聚聚类算法评估血浆和痰液细胞因子测定中的患者聚类情况。

结果

本初步研究共纳入13例患者。聚类分析确定了血浆、痰液以及血浆与痰液比值中细胞因子的不同炎症反应模式。

结论

住院CAP患者血浆和痰液中的炎症反应模式可以确定。局部和全身炎症反应的特征可能有助于更好地筛选患者纳入免疫调节治疗的临床试验。

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