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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要目前对危重疾病进行分类的方法侧重于广泛的临床综合征，包括脓毒症和急性呼吸窘迫综合征（ARDS）。然而，这些共识定义的应用综合征尚未转化为针对综合征的靶向治疗。最近的变革性研究 ARDS 揭示了潜在的（潜在的）生物表型，称为高炎症和低炎症，即多个 ARDS 队列之间的结果非常一致。此外，在事后分析中，这些表型响应与护理过程（液体、PEEP）和药物（辛伐他汀）治疗不同。这些发现表明ARDS、肺炎和败血症的生物表型可能为更深层次的研究铺平道路对危重疾病生物学的理解将首次转化为有针对性的、个性化的疗法。我们的多学科研究团队和临床招募中心汇集了深入的研究人员 ARDS、败血症和肺炎的病理生理机制和表型的科学专业知识，世界各地用于收集重大疾病后长期结果的一流基础设施，丰富的设计经验和实施观察性临床队列研究，包括长期随访和经过验证的入组能力大量危重患者正在进行观察和临床研究。我们的团队提出了两项研究：(1) 联盟范围内的 5,000 名患者观察性队列研究，重症监护中的多维度表型分析（音乐）学习。本研究的主要目的是检验潜在表型可推广的假设跨越危重疾病综合症并与短期和长期结果相关。判断是否炎症表型在常见的危重疾病综合征中是可识别的，可以从根本上改变我们的以捕获更统一的生物表型不可知论的方式对危重疾病进行分类的方法综合征诊断。 (2) 一项临床中心研究，旨在满足更好地了解空域的迫切需求 ARDS 和其他急性呼吸衰竭 (ARF) 病因患者的生物学。早已是认识到空域生物学与循环生物学有很大不同，但该领域缺乏非一种侵入性、廉价、简单且安全的 ARF 远端空域采样方法。我们组有首创了一种对 ARF 插管、机械通气患者的气腔进行采样的新方法使用从热湿交换器 (HME) 过滤器中提取的流体。 HARMONY 研究（HME 治疗急性呼吸衰竭多维表型分析的主要目标是识别肺部特异性表型在 ARF 中，将测试其与长期功能性和结构性呼吸结果的关联。我们的中心将利用我们在危重疾病表型分析方面的专业知识、强大的 ED/ICU 患者入组（37,756 5 年内的患者），在 ICU 幸存者长期结果方面的开创性工作，数十年的研究经验危重疾病的生物标志物和研究空域生物学的新方法，在 APS 中发挥关键作用该联盟在 ARDS、肺炎和败血症领域具有重大且持续的影响。