The MUltidimenSional phenotyping In Critical care (MUSIC) Consortium: A pathway to precision medicine at the bedside

重症监护 (MUSIC) 多维度表型分析联盟：床边精准医疗的途径

• 批准号: 10649995
• 负责人: Lorraine B Ware
• 金额: $ 19.43万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2029-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649995
• 关键词: Acute Respiratory Distress Syndrome; Acute respiratory failure; Address; Alveolar; Biological; Biological Markers; Biology; Caring; Circulation; Classification; Clinical; Clinical Research; Clinical Trials; Cognitive; Cohort Studies; Collection; Consensus; Critical Care; Critical Illness; Data; Diagnosis; Dimensions; Distal; Endothelium; Enrollment; Environmental Exposure; Environmental Risk Factor; Epithelium; Etiology; Functional disorder; Goals; Heterogeneity; Hospitals; Image; Infection; Inflammatory; Infrastructure; Injury; Institution; Integration Host Factors; Intervention; Intubation; Knowledge; Liquid substance; Longterm Follow-up; Lung; Measures; Mechanical ventilation; Methods; Modeling; National Heart, Lung, and Blood Institute; Observational Study; Organ; Outcome; Pathway interactions; Patient observation; Patients; Phase; Phenotype; Plasma; Play; Pneumonia; Positive-Pressure Respiration; Predisposing Factor; Process; Pulmonary function tests; Recovery; Research Personnel; Respiratory Failure; Respiratory physiology; Resuscitation; Sampling; Sepsis; Simvastatin; Site; Socioeconomic Factors; Survivors; Syndrome; Testing; Therapeutic; Time; Translating; Ventilator; Work; clinical center; cohort; design; experience; individual patient; insight; lung imaging; machine learning model; multidisciplinary; novel; novel strategies; observational cohort study; participant enrollment; personalized medicine; pharmacologic; precision medicine; prognostication; respiratory; response; septic patients; targeted treatment; tool; ventilation

PROJECT SUMMARY Current approaches to classifying critical illness focus on broad clinical syndromes including sepsis and the acute respiratory distress syndrome (ARDS). However, application of consensus definitions of these syndromes has not translated to syndrome-specific, targeted therapies. Recent transformative studies of ARDS have revealed underlying (latent) biological phenotypes, termed hyper- and hypo-inflammatory, that are remarkably consistent across multiple ARDS cohorts. Further, in post hoc analysis, these phenotypes respond differentially to both process of care (fluids, PEEP) and pharmacologic (simvastatin) treatments. These findings suggest that biological phenotyping in ARDS, pneumonia and sepsis may pave the way towards a deeper understanding of the biology of critical illness that will translate, for the first time, into targeted, personalized therapies. Our multidisciplinary team of investigators and clinical enrollment sites brings together deep scientific expertise in pathophysiologic mechanisms and phenotyping of ARDS, sepsis and pneumonia, world- class infrastructure for collecting long-term outcomes after critical illness, strong experience in designing and implementing observational clinical cohort studies that include long-term follow-up, and proven ability to enroll large numbers of critically ill patients in observational and clinical studies. Our team proposes two studies: (1) a Consortium-wide 5,000 patient observational cohort study, the MUltidimenSional phenotyping In Critical care (MUSIC) Study. The primary Aim of this study is to test the hypothesis that latent phenotypes are generalizable across critical illness syndromes and associate with both short- and long-term outcomes. Determining whether inflammatory phenotypes are identifiable across common critical illness syndromes can fundamentally alter our approach to classifying critical illness in a way that captures a more uniform biological phenotype agnostic to syndromic diagnosis. (2) a Clinical Center Study that addresses the critical need to better understand airspace biology in patients with ARDS and other etiologies of acute respiratory failure (ARF). It has long been recognized that airspace biology differs significantly from that of the circulation, but the field has lacked a non- invasive, inexpensive, simple, and safe method of sampling the distal airspace in ARF. Our group has pioneered a new method for sampling the airspace in intubated, mechanically ventilated patients with ARF using fluid extracted from heat moisture exchanger (HME) filter. The HARMONY study (HME for Acute Respiratory failure MultidimensiONal phenotYping) has a primary goal of identifying lung-specific phenotypes in ARF that will be tested for associations with long term functional and structural respiratory outcomes. Our Center will leverage our expertise in critical illness phenotyping, robust ED/ICU patient enrollment (37,756 patients in 5 years), pioneering work in long term outcomes in ICU survivors, decades of experience studying biomarkers of critical illness and novel approaches to study airspace biology, to play a key role in the APS Consortium and have a major and sustained impact in the field of ARDS, pneumonia, and sepsis.

项目摘要 当前对重症疾病分类的方法集中在广泛的临床综合征上，包括败血症和 急性呼吸窘迫综合征（ARDS）。但是，应用这些共识定义 综合征尚未转化为综合征特异性的靶向疗法。最近的变革性研究 ARDS揭示了基本的（潜在）生物学表型，称为超级和低炎症性 在多个ARDS队列中非常一致。此外，在事后分析中，这些表型反应 与护理过程（流体，窥视）和药理学（辛伐他汀）治疗不同。这些发现 建议在ARDS，肺炎和败血症中进行生物学表型，可能会铺平到更深层次的道路 了解将首次转化为有针对性的个性化的重症疾病的生物学 疗法。我们的调查人员和临床入学站点组成的多学科团队将 ARDS，败血症和肺炎的病理生理机制和表型的科学专业知识，世界 - 班级基础设施用于在重症疾病后收集长期成果，设计和设计丰富的经验 实施包括长期随访的观察性临床队列研究，并具有验证的能力 在观察和临床研究中，大量重病患者。我们的团队提出了两项​​研究：（1） 整个财团的5,000例患者观察队列研究，重症监护中的多维表型 （音乐）研究。这项研究的主要目的是检验潜在表型可推广的假设 跨关键疾病综合征，并与短期和长期结局相关。确定是否 炎症表型在常见的危害疾病综合征中可以识别为可以改变我们的 以一种捕获更统一的生物学表型不可知论的方式对危害疾病进行分类的方法 综合征诊断。 （2）一项临床中心研究，该研究解决了更好地了解领空的关键需求 急性呼吸衰竭（ARF）患者的生物学和其他病因。长期以来已经 认识到空域生物学与循环的生物学明显不同，但是该领域缺乏非 - 侵入性，廉价，简单且安全的方法，用于在ARF中采样远端领空。我们的小组有 开创了一种新的方法，用于在插管，机械通风的ARF患者中取得空域 使用从热水分交换器（HME）过滤器中提取的液体。和谐研究（急性HME 呼吸衰竭多维表型）的主要目标是识别肺特异性表型 在ARF中，将测试与长期功能和结构呼吸结果的关联。我们的 中心将利用我们在重症疾病表型，强大的ED/ICU患者入学率方面的专业知识（37,756 5年的患者），在ICU幸存者中长期成果的开创性工作，数十年的研究经验 重症疾病的生物标志物和研究空域生物学的新方法，在APS中发挥关键作用 财团，对ARDS，肺炎和败血症领域产生重大持续的影响。