Plasma Nucleosomes Are Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome.
Plasma Nucleosomes Are Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome.
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DOI：
10.1097/ccm.0000000000004923
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发表时间：
2021-07-01
影响因子：
8.8
通讯作者：
Christie JD
中科院分区：
文献类型：
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作者：
Yehya N;Fazelinia H;Lawrence GG;Spruce LA;Mai MV;Worthen GS;Christie JD
循环核小体及其组成组蛋白被认为是成人脓毒症和急性呼吸窘迫综合征（ARDS）的致病因素。然而，它们在儿科 ARDS 中的作用尚不清楚。我们对 ARDS 儿童进行了一项前瞻性队列研究，在 ARDS 发病后 24 小时内采集血浆。我们将核小体水平与 ARDS 的严重程度和非肺器官衰竭相关联，并在单变量和多变量分析中测试了核小体与儿科重症监护病房 (PICU) 死亡率和 28 天无呼吸机天数 (VFD) 的关联。我们还在患有或不患有 ARDS 的脓毒症儿童的匹配病例对照研究中对 DNA 结合血浆蛋白进行了蛋白质组学，以鉴定 ARDS 中升高的特定组蛋白。大型学术三级护理 PICU。符合柏林ARDS标准的插管儿童。没有任何。我们招募了 333 名患有 ARDS 的儿童，其中 69 名 (21%) 没有幸存。血浆核小体与 ARDS 严重程度以及 ARDS 发作时非肺器官衰竭的数量相关。相对于幸存者 (0.10 [IQR 0.04, 0.25] AU)，非幸存者 (0.40 [四分位距 0.20, 0.71] 任意单位) 的核小体较高 (p < 0.001)。在多变量分析中，核小体与 PICU 死亡率相关（调整后的比值比每增加 1 个标准差为 1.84，95% 置信区间为 1.38 至 2.45，p < 0.001）。多变量调整后，核小体还与第 28 天时存活拔管的概率较低相关（调整后的次分布风险比 0.74，95% CI 0.63 至 0.88，p = 0.001）。蛋白质组学分析表明，与不患有 ARDS 的脓毒症儿童相比，患有 ARDS 的脓毒症儿童的核心核小体组蛋白 H2A、H2B、H3 和 H4 水平较高。血浆核小体与 ARDS 严重程度、非肺器官衰竭以及儿科 ARDS 的不良结局相关。
Circulating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome (ARDS) in adults. However, their role in pediatric ARDS is unknown. We performed a prospective cohort study in children with ARDS, with plasma collection within 24 hours of ARDS onset. We associated nucleosome levels with severity of ARDS and with non-pulmonary organ failures and tested for association of nucleosomes with pediatric intensive care unit (PICU) mortality and ventilator-free days (VFDs) at 28 days in univariate and multivariable analysis. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without ARDS in order to identify specific histone proteins elevated in ARDS. Large academic tertiary care PICU. Intubated children meeting Berlin criteria for ARDS. None. We enrolled 333 children with ARDS, with 69 (21%) non-survivors. Plasma nucleosomes were correlated with ARDS severity and with the number of non-pulmonary organ failures at ARDS onset. Nucleosomes were higher (p < 0.001) in non-survivors (0.40 [interquartile range 0.20, 0.71] arbitrary units) relative to survivors (0.10 [IQR 0.04, 0.25] AU). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 standard deviation increase, 95% confidence interval 1.38 to 2.45, p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio 0.74, 95% CI 0.63 to 0.88, p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with ARDS, relative to septic children without ARDS. Plasma nucleosomes are associated with ARDS severity, non-pulmonary organ failures, and worse outcomes in pediatric ARDS.