Precision Medicine for Nutrition in EDEN

EDEN 的精准营养医学

• 批准号: 10644738
• 负责人: Faraaz Ali Shah
• 金额: $ 11.93万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644738
• 关键词: Acute Lung Injury; Acute Respiratory Distress Syndrome; Advocate; Affect; Biological; Biological Assay; Biological Markers; Biological Specimen Banks; Caring; Categories; Clinical; Complex; Computer Models; Critical Care; Critical Illness; Data; Dietary Intervention; Disease; Endocrine; Enrollment; Enteral; Enteral Feeding; Enteral Nutrition; Feeds; Funding; Future; Gastric Inhibitory Polypeptide; Goals; Guidelines; Heterogeneity; Hormones; Hyperglycemia; Immune response; Individual; Inflammation; Inflammatory; Insulin; Intake; Intestinal permeability; Intestines; Investigation; Ischemia; Knowledge; Laboratories; Life; Liquid substance; Methodology; Modeling; Multicenter Trials; National Heart, Lung, and Blood Institute; Nausea and Vomiting; Nutrient; Nutrition Therapy; Nutritional Study; Observational Study; Outcome; Participant; Pathway interactions; Patients; Pattern; Permeability; Persons; Phenotype; Physical Function; Physiological; Population; Prediction of Response to Therapy; Process; Prognosis; Randomized; Recommendation; Recovery; Risk; Route; Secondary to; Severity of illness; Stomach; Testing; Thinness; adverse outcome; cell motility; demographics; frontier; gastrointestinal; glucagon-like peptide 1; glucose metabolism; gut inflammation; improved; incretin hormone; individual patient; insulin secretion; intestinal fatty acid binding protein; lung injury; mortality; muscle form; next generation; novel; nutrition; personalized care; precision medicine; precision nutrition; predictive marker; prevent; response; secondary analysis; standard of care; systemic inflammatory response; treatment effect; treatment response; ventilation

PROJECT ABSTRACT Nutrition is an essential component in the care of critically ill patients with acute respiratory distress syndrome (ARDS) who are often limited in volitional intake and who incur new deficits in physical function secondary to their illness. Despite well-characterized associations between inadequate nutrition and adverse outcomes, large multicenter trials of specific nutrition strategies have failed to consistently demonstrate clinical benefit with any particular approach. The landmark NHLBI-funded Early versus Delayed Enteral Nutrition [EDEN] trial investigated low-level (trophic) versus full enteral feeds in 1000 patients and demonstrated increased gastrointestinal complications with full enteral feeds without any clinical benefit. Subsequently, current guidelines recommend low-level feeds for all ARDS patients, however, ARDS is increasingly recognized as a heterogeneous disease and a one-size-fits-all approach may not be appropriate. An essential first step in individualizing nutrition in ARDS is identifying the clinical and biologic variables that contribute to heterogeneity of treatment effect whereby individuals or groups vary in response to treatment. Thus, the overall goal of this proposal is to characterize differential responses to nutrition by leveraging data and biospecimens from the EDEN trial. In Aim 1, this proposal will investigate whether ARDS subphenotypes differed in response to low- level versus full enteral nutrition in EDEN. Recent studies have identified two distinct ARDS subphenotypes that differ in prognosis, host response, and potentially in response to treatments. ARDS subphenotypes have not been investigated with regards to nutrition. Thus, Aim 1 will perform biologic assays to facilitate ARDS subphenotype identification and will test for differences by subphenotype in clinical outcomes, in intestinal permeability, and in incretin hormones. When released at physiologic levels in response to enteral nutrients, incretins have beneficial effects on insulin release and glucose metabolism, but when released at supraphysiologic levels in response to intestinal inflammation, incretins may worsen tolerance to nutrition by reducing gastric motility. Incretins are not well characterized in ARDS. In Aim 2, this proposal will use computational approaches that directly model individual treatment effects based on patient covariates allowing for investigations of treatment response that result from a complex interaction between baseline demographics, severity of illness, endocrine hormones, and inflammation at an individual patient level. Successful completion of the proposed Aims will provide new knowledge on biologic responses to nutrition strategies, identify mechanisms that contribute to heterogeneity of treatment effect at an individual level, and provide direction for the next generation of precision nutrition studies in ARDS.

项目摘要 营养是护理急性呼吸窘迫综合症患者的重要组成部分 （ARDS）通常受到自愿摄入量的限制，并在其身体功能上遇到新的缺陷 他们的病。尽管营养和不良结果之间的交流充分，但 特定营养策略的大型多中心试验未能始终如一地证明临床益处 采用任何特定的方法。具有里程碑意义的NHLBI资助的早期与延迟的肠内营养[Eden]试验 研究了1000名患者的低水平（营养）与全肠内饲料的研究，并证明有所增加 胃肠道并发症具有完整的肠内饲料，没有任何临床益处。随后，当前 指南建议为所有ARDS患者提供低级饲料，但是，ARDS越来越被认为是 异质性疾病和一种千篇一律的方法可能不合适。重要的第一步 ARDS中的个性化营养正在识别有助于异质性的临床和生物学变量 治疗效果，个人或组因治疗而变化。因此，总体目标 提案是通过利用数据和生物测量来表征对营养的差异反应 伊甸园试验。在AIM 1中，该提案将调查ARDS亚表现型在低 - 响应中是否有所不同 伊甸园的水平与全肠营养。最近的研究已经确定了两种不同的ARDS亚表征 这在预后，宿主反应以及对治疗的响应中有所不同。 ARDS亚表现型具有 没有对营养进行调查。因此，AIM 1将执行生物学测定以促进ARDS 亚表格型识别，并将在肠道中测试亚表征的差异 渗透性和内导素激素。响应肠内营养以生理水平发行时， 肠静脉素对胰岛素释放和葡萄糖代谢具有有益的作用，但是在释放时 超生理水平响应肠道炎症，肠降凝结素可能会使对营养的耐受性恶化 降低胃运动。肠静脉毒素在ARDS中的表征没有很好。在AIM 2中，该建议将使用 根据患者协变量直接对个体治疗效应进行建模的计算方法，允许 为了研究基线人口统计学之间复杂相互作用导致的治疗反应， 疾病的严重程度，内分泌激素和个别患者水平的炎症。成功完成 拟议的目的将提供有关营养策略生物学反应的新知识，确定 有助于在个人层面上有助于治疗效应的异质性的机制，并为 下一代ARDS中的精确营养研究。