A transcriptomic approach to understand patient susceptibility to pneumonia after abdominal surgery
A transcriptomic approach to understand patient susceptibility to pneumonia after abdominal surgery
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通过转录组学方法了解腹部手术后患者对肺炎的易感性
DOI：
10.1101/2023.01.25.23284914
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Torrance H
中科院分区：
文献类型：
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作者：
Torrance H
目的：描述腹部大手术后免疫途径和基因网络的改变，并确定与术后肺炎相关的转录组模式。背景：院内感染是一项重大的医疗保健挑战，在 45 岁或以上接受腹部大手术的患者中，超过 20% 发生院内感染，而术后肺炎与 30 天死亡率增加近 5 倍相关。方法：从接受腹部大手术的前瞻性连续队列 (n = 150) 中，在术前和术中收集全血 RNA术后 3 个时间点（2-6、24 和 48 小时）。通过 RNA 测序鉴定出 12 例诊断为术后肺炎的患者和 27 例匹配的无感染患者进行分析。结果：与术前采样相比，2 至 6 小时有 3639 个基因上调，5043 个基因下调。通路分析表明先天免疫激活伴随中性粒细胞脱颗粒和 Toll 样受体信号上调以及适应性免疫抑制。术前 RNA 测序的细胞类型解卷积显示，在后来发展为肺炎的患者中，S100A8/9 高中性粒细胞升高，同时幼稚 CD4 T 细胞减少。术前，中性粒细胞脱粒的基因特征与术后肺炎的发生相关（P = 0.00092）。先前报道的脓毒症反应特征 (SRSq) 评分反映了术后 48 小时中性粒细胞功能障碍和宿主反应失调，随后出现肺炎的患者与未感染的患者之间存在差异 (P = 0.045)。对独立腹部大手术和多发伤队列中新的中性粒细胞基因特征和 SRSq 评分的分析表明，在识别后期感染患者方面具有良好的预测性能。结论：腹部大手术急剧上调先天免疫途径，同时抑制适应性免疫途径。这在发生术后肺炎的患者中更为突出。术前中性粒细胞脱颗粒特征的转录组学特征和术后 SRSq 评分可能是随后肺炎风险的有用预测因子。
Objective:To describe immune pathways and gene networks altered following major abdominal surgery and to identify transcriptomic patterns associated with postoperative pneumonia.Background:Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major abdominal surgery, with postoperative pneumonia associated with an almost 5-fold increase in 30-day mortality.Methods:From a prospective consecutive cohort (n= 150) undergoing major abdominal surgery, whole-blood RNA was collected preoperatively and at 3 time-points postoperatively (2–6, 24, and 48 h). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing.Results:Compared to preoperative sampling, 3639 genes were upregulated and 5043 downregulated at 2 to 6 hours. Pathway analysis demonstrated innate-immune activation with neutrophil degranulation and Toll-like-receptor signaling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil degranulation was associated with postoperative pneumonia acquisition (P= 0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil dysfunction and a more dysregulated host response, at 48 hours postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P= 0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection.Conclusions:Major abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.