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 营养是治疗急性呼吸窘迫综合征危重患者的重要组成部分 （ARDS）他们的意志摄入量经常受到限制，并且继发于身体功能的新缺陷 他们的病。尽管营养不足与不良后果之间存在明确的关联， 特定营养策略的大型多中心试验未能一致证明临床益处 与任何特定的方法。由 NHLBI 资助的具有里程碑意义的早期与延迟肠内营养 [EDEN] 试验 对 1000 名患者进行了低水平（营养性）肠内喂养与全肠内喂养的比较，结果表明 全肠内喂养的胃肠道并发症没有任何临床益处。随后，当前 指南建议所有 ARDS 患者低水平喂养，然而，ARDS 越来越被认为是一种 异质性疾病和一刀切的方法可能并不合适。重要的第一步 ARDS 中的个体化营养是确定导致异质性的临床和生物学变量 个人或群体对治疗的反应各不相同的治疗效果。因此，本次活动的总体目标是 提议是通过利用来自以下领域的数据和生物样本来描述对营养的不同反应 伊甸园审判。在目标 1 中，该提案将调查 ARDS 亚表型是否因低浓度反应而有所不同。 水平与 EDEN 中的全肠内营养的比较。最近的研究发现了两种不同的 ARDS 亚表型 不同的预后、宿主反应以及对治疗的潜在反应。 ARDS 亚表型有 没有进行过营养方面的调查。因此，目标 1 将进行生物测定以促进 ARDS 亚表型鉴定，并将测试亚表型在临床结果、肠道中的差异 渗透性和肠促胰岛素激素。当响应肠内营养物以生理水平释放时， 肠降血糖素对胰岛素释放和葡萄糖代谢具有有益作用，但当释放时 肠促胰岛素的超生理水平对肠道炎症的反应可能会恶化营养耐受性 减少胃蠕动。肠促胰岛素在 ARDS 中的特征尚不明确。在目标 2 中，该提案将使用 基于患者协变量直接模拟个体治疗效果的计算方法，允许 用于调查基线人口统计数据之间复杂相互作用所产生的治疗反应， 患者个体的疾病严重程度、内分泌激素和炎症。顺利完成 拟议目标将提供有关营养策略的生物反应的新知识，确定 导致个体水平治疗效果异质性的机制，并为治疗提供方向 ARDS 的下一代精准营养研究。