A Lipid Map for Community-acquired Pneumonia with Sepsis: Observation Is the First Step in Scientific Progress.
A Lipid Map for Community-acquired Pneumonia with Sepsis: Observation Is the First Step in Scientific Progress.
复制标题
社区获得性肺炎脓毒症的血脂图：观察是科学进步的第一步。
DOI：
10.1164/rccm.202401-0213ed
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发表时间：
2024
影响因子：
24.7
通讯作者：
Wheelock,CraigE
中科院分区：
文献类型：
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作者：
Schenck,EdwardJ;Plataki,Maria;Wheelock,CraigE
在美国，社区获得性肺炎（CAP）伴脓毒症每年导致超过35万人入住重症监护室（ICU），住院死亡率为17%，一年死亡率接近50% 1。有一个未满足的需求，以解开决定疾病严重程度和驱动不良后果的分子过程2。NHLBI呼吁使用生物“组学”特征来开发肺炎的相关“风险组学”，以了解宿主对严重疾病易感性的病理生物学3。在COVID-19大流行的早期阶段，反向翻译，包括多个“组学”分析，直接导致了有效的治疗策略。具体而言，脂质组学方法鉴定了许多与疾病严重程度相关的循环脂质，并提供了对宿主对感染反应的深入了解4。尽管这种方法在COVID中取得了成功，但在严重的CAP 5中仍然相对不足。在这里，Chouchane及其同事对150多名因CAP 6而患有危重病的患者进行了全面的，非靶向的血浆脂质组学评估。目的是通过询问脂质如何区分风险以及它们如何在不同的临床轨迹过程中变化来增加我们对脓毒症病理生理学的理解。更直接地说，他们试图创建一个脂质组学图谱，以指导我们从床边到工作台。研究人员对入选脓毒症分子诊断和风险分层（MARS）队列的严重CAP患者进行了基于高分辨率质谱的脂质组学分析。先前从两个独立的外部队列（社区获得性肺炎和脓毒症结局诊断（CAPSOD 5）和肾和肺损伤早期评估（EARLI 7））中测量的血脂作为有效指标。这些患者代表了在高收入国家ICU中发现的患者以及那些有资格在这些地区进行治疗性临床试验的患者。主要队列包括感染阴性ICU对照和健康对照。
Community acquired pneumonia (CAP) with sepsis leads to over 350 thousand intensive care unit (ICU) admissions in the USA annually, with an in-hospital mortality of 17% and a one-year mortality of nearly 50% 1. There is an unmet need to disentangle the molecular processes that determine disease severity and drive adverse outcomes2. The NHLBI has called for the use of biologic “omic” profiles to develop relevant “risk-omes” for pneumonia to understand the pathobiology of host susceptibility to severe disease3. Backward translation, including multiple “omics” analyses, during the early stages of the COVID-19 pandemic led directly to effective therapeutic strategies. Specifically, lipidomic approaches identified numerous circulating lipids that correlate to disease severity and provided insight into host response to infection4. Despite the success of this approach in COVID, it remains relatively under evaluated in severe CAP5. Here, Chouchane and colleagues present a comprehensive, untargeted, plasma lipidomic evaluation of over 150 patients with critical illness due to CAP6. The goal was to add to our understanding of sepsis pathophysiology by interrogating how lipids can differentiate risk and how they change over the course of divergent clinical trajectories. More directly, they sought to create a lipidomic map to guide us from the bedside to the bench.The investigators performed high resolution mass spectrometry-based lipidomic analyses on well phenotyped, serial samples from patients with severe CAP enrolled in the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) cohort. Previously measured lipids from two separate external cohorts, the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD5) and the Early Assessment of Renal and Lung Injury (EARLI7) served as validaiton. The patients are representative of those found in high-income country ICUs and those eligible for therapeutic clinical trials in those locations. The primary cohort included infection-negative ICU controls and healthy controls.