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Comparative Analysis of the Host Response to Community-acquired and Hospital-acquired Pneumonia in Critically Ⅲ Patients

机译:Ⅲ类重症患者社区获得性和医院获得性肺炎宿主反应的比较分析

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摘要

Rationale: Preclinical studies suggest that hospitalized patients are susceptible to infections caused by nosocomial respiratory pathogens at least in part because of immune suppression caused by the condition for which they were admitted. Objectives: We aimed to characterize the systemic host response in hospital-acquired pneumonia (HAP) when compared with community-acquired pneumonia (CAP). Methods: We performed a prospective study in two intensive care units (ICUs) in 453 patients with HAP (n = 222) or CAP (n = 231). Immune responses were determined on ICU admission by measuring 19 plasma biomarkers reflecting organ systems implicated in infection pathogenesis (in 192 patients with HAP and 183 patients with CAP) and by applying genome-wide blood gene expression profiling (in 111 patients with HAP and 110 patients with CAP). Measurements and Main Results: Patients with HAP and CAP presented with similar disease severities and mortality rates did not differ up to 1 year after admission. Plasma proteome analysis revealed largely similar responses, including systemic inflammatory and cytokine responses, and activation of coagulation and the vascular endothelium. The blood leukocyte genomic response was greater than 75% common in patients with HAP and CAP, comprising proinflammatory, antiinflammatory, T-cell signaling, and metabolic pathway gene sets. Patients with HAP showed overexpression of genes involved in cell-cell junction remodeling, adhesion, and diapedesis, which corresponded with lower plasma levels of matrix metalloproteinase-8 and soluble E-selectin. In addition, patients with HAP demonstrated underexpression of a type-Ⅰ interferon signaling gene signature. Conclusions: Patients with HAP and CAP present with a largely similar host response at ICU admission.
机译:理由:临床前研究表明,住院患者对医院呼吸道病原体引起的感染易感,至少部分原因是由于入院条件引起的免疫抑制。目的:与社区获得性肺炎(CAP)相比,我们旨在表征医院获得性肺炎(HAP)的全身宿主反应。方法:我们在两个重症监护病房(ICU)中对453名HAP(n = 222)或CAP(n = 231)患者进行了前瞻性研究。通过测量19种血浆生物标志物来反映ICU入院时的免疫反应,这些标志物反映了与感染发病机制有关的器官系统(在192例HAP患者和183例CAP患者中)以及应用全基因组血液基因表达谱分析(在111例HAP患者和110例患者CAP)。测量和主要结果:入院后1年内,HAP和CAP疾病严重程度和死亡率相似的患者无差异。血浆蛋白质组学分析显示出基本相似的反应,包括全身性炎症反应和细胞因子反应,以及凝血和血管内皮的激活。 HAP和CAP患者的血液白细胞基因组应答普遍超过75%,包括促炎,抗炎,T细胞信号传导和代谢途径基因组。患有HAP的患者显示出与细胞-细胞连接重塑,粘附和尿布分离有关的基因的过表达,这与血浆中的基质金属蛋白酶8和可溶性E-选择素的血浆水平较低相对应。此外,患有HAP的患者表现出I型干扰素信号传导基因签名的低表达。结论:HIC和CAP患者在ICU入院时表现出与宿主相似的宿主反应。

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  • 作者单位

    Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;

    Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;

    Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;

    Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;

    Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands,Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands,Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands;

    Cologne Center for Genomics, University of Cologne, Cologne, Germany,Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany;

    Cologne Center for Genomics, University of Cologne, Cologne, Germany;

    Cologne Center for Genomics, University of Cologne, Cologne, Germany,Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;

    Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands;

    Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;

    Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;

    Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands;

    Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands,Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    pneumonia; sepsis; genomics; critically ill; intensive care unit;

    机译:肺炎;败血症基因组学重病重症监护室;

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