Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: secondary analysis of a randomised controlled trial
Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: secondary analysis of a randomised controlled trial
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DOI：
10.1183/13993003.01389-2017
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发表时间：
2018-04-01
影响因子：
24.3
通讯作者：
Hasler, Paul
中科院分区：
文献类型：
--
作者：
Ebrahimi, Fahim;Giaglis, Stavros;Hasler, Paul
中性粒细胞胞外陷阱（NET）是炎症性疾病中免疫反应的标志。然而，NETs 在社区获得性肺炎 (CAP) 中的作用尚不清楚。本研究旨在描述 NET 对肺炎临床结果的影响。这是一项随机对照、多中心试验的二次分析。 CAP 患者被随机分配接受 50 mg 泼尼松或安慰剂治疗，为期 7 天。主要终点是达到临床稳定的时间；主要次要终点是住院时间和死亡率。分析总共包括 310 名患者。作为 NETosis 替代标志物的无细胞核小体水平在入院时显着增加，并在 7 天内下降。在多变量调整分析中，NET 与临床稳定性和出院风险的降低显着相关。此外，NET 与 30 天死亡率调整后比值比增加 3.8 倍相关。泼尼松治疗改变了循环 NET 水平，并与有益的结果相关。CAP 伴随着明显的 NET 形成。血清 NET 标志物升高的患者出现临床不稳定、住院时间延长和 30 天全因死亡率的风险较高。 NET 代表了一种新的结果标记，也是肺炎辅助治疗的可能目标。
Neutrophil extracellular traps (NETs) are a hallmark of the immune response in inflammatory diseases. However, the role of NETs in community-acquired pneumonia (CAP) is unknown. This study aims to characterise the impact of NETs on clinical outcomes in pneumonia.This is a secondary analysis of a randomised controlled, multicentre trial. Patients with CAP were randomly assigned to either 50 mg prednisone or placebo for 7 days. The primary end-point was time to clinical stability; main secondary end-points were length of hospital stay and mortality.In total, 310 patients were included in the analysis. Levels of cell-free nucleosomes as surrogate markers of NETosis were significantly increased at admission and declined over 7 days. NETs were significantly associated with reduced hazards of clinical stability and hospital discharge in multivariate adjusted analyses. Moreover, NETs were associated with a 3.8-fold increased adjusted odds ratio of 30-day mortality. Prednisone treatment modified circulatory NET levels and was associated with beneficial outcome.CAP is accompanied by pronounced NET formation. Patients with elevated serum NET markers were at higher risk for clinical instability, prolonged length of hospital stay and 30-day all-cause mortality. NETs represent a novel marker for outcome and a possible target for adjunct treatments of pneumonia.