Great Lakes Clinical Center of the Acute Respiratory Distress Syndrome, Pneumonia and Sepsis (APS) Consortium

急性呼吸窘迫综合征、肺炎和败血症 (APS) 联盟五大湖临床中心

• 批准号: 10646578
• 负责人: Robert Pickett Dickson
• 金额: $ 15.29万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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/10646578
• 关键词: Acute; Acute Respiratory Distress Syndrome; Antibiotics; Bioinformatics; Biological; Blood; Body Composition; Catchment Area; Chest imaging; Chicago; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Collection; Communicable Diseases; Communication; Critical Care; Critical Illness; Curettage procedure; DNA; Data; Data Collection; Databases; Development; Discipline; Disease; Early Mobilizations; Emergency Medicine; Enrollment; Ensure; Event; Feces; Future; Geography; Health system; Healthcare; Heterogeneity; Hospitalization; Hospitals; Hybrids; Hyperoxia; Image; Immunology; Infection; Intervention; Leadership; Life; Longitudinal cohort study; Longterm Follow-up; Lung; Measures; Mediating; Mediator; Medicine; Metabolic; Metabolic Pathway; Methodology; Michigan; Microbiology; Molecular; Morbidity - disease rate; Nasal Epithelium; Observational Study; Outcome; Pathway interactions; Patient observation; Patient-Focused Outcomes; Patients; Persons; Pharmacy facility; Phenotype; Physical Function; Pneumonia; Positioning Attribute; Prevention; Process; Protocols documentation; Pulse Oximetry; Qualifying; RNA; Recovery; Research; Research Personnel; Respiratory System; Role; Scientific Inquiry; Sepsis; Severity of illness; Site; Source; Specimen; Survivors; Syndrome; Techniques; Telephone; Therapeutic; Time; Universities; Variant; Visit; X-Ray Computed Tomography; aspirate; biological heterogeneity; clinical biomarkers; clinical care; clinical center; clinical heterogeneity; clinical research site; cohort; cost; cytokine; endotracheal; experience; follow-up; functional status; gut microbiome; gut microbiota; hospital readmission; improved; indexing; innovation; long term recovery; microbial; microbiome; mortality; novel; observational cohort study; pharyngeal swab; prospective; respiratory microbiota; response; sample collection; septic patients; skin color; targeted treatment; transcriptomics

PROJECT SUMMARY The Acute Respiratory Distress Syndrome (ARDS), pneumonia and sepsis are life-threatening conditions whose clinical and biological manifestations are frequently interwoven: pneumonia is a common cause of sepsis, and both are predisposing conditions for ARDS. While progress has been made to reduce mortality in these conditions, their significant heterogeneity is a major factor limiting therapeutic progress. Future interventions must be informed by an improved understanding of phenotypes and endotypes within these conditions to better design clinical trials. The proposed Great Lakes Clinical Center (GLCC) of the ARDS, Pneumonia and Sepsis (APS) Consortium, consisting of the University of Michigan, Henry Ford Hospital, the University of Cincinnati, and the University of Chicago will screen, enroll, collect data and transport biospecimens on at least 1000 patients of this 5000-patient observational study over a 6-year period. Clinical information and biospecimens from the index hospitalization and from long-term follow up at 3, 6 and 12 months will be collected. Biospecimens will include blood, stool, pharyngeal swabs, and endotracheal aspirates. Specimens will be transported to the Clinical Coordinating Center for storage and future analysis. The rich database we propose will provide investigators with innumerable opportunities to biologically interrogate the heterogeneity of APS patients. Included in this database are opportunities for investigators to study clinical disease trajectories; blood cytokines, DNA, RNA, and metabolites; gastrointestinal and respiratory microbiota; and chest and body imaging. In addition, we propose two unique data collection approaches: morphometric characterization of CT images (to rigorously characterize body composition) and nasal epithelial curettage (to study the host transcriptomic response within the respiratory tract). We also propose a Center-specific study that will elucidate the role of the microbiome in the development, trajectory, and recovery of ARDS, pneumonia, and sepsis. The microbiome is an important yet incompletely understood source of biologic heterogeneity, and represents a highly promising treatment target. Yet we lack an actionable understanding of its role in these conditions. Our team will leverage the above-described specimen and data collection with field-leading methodological expertise to (Aim 1) identify the pathways by which gut and respiratory microbiota participate in the acute development and trajectory of sepsis, ARDS, and pneumonia and (Aim 2) determine the microbial and metabolic pathways by which gut microbiota influence long-term recovery after these conditions. We will use cutting-edge molecular techniques to characterize the microbiome and its metabolic products, and we will use sophisticated causal inference analyses to study the mediating role of the microbiome in clinical outcomes. By interrogating the role of the microbiome in the development, trajectory, and recovery of these conditions, this project will facilitate the development of microbiome-targeted therapies for their prevention and treatment.

项目概要 急性呼吸窘迫综合征 (ARDS)、肺炎和败血症是危及生命的疾病 其临床和生物学表现经常交织在一起：肺炎是引起以下疾病的常见原因 败血症，两者都是 ARDS 的诱发因素。尽管在降低死亡率方面取得了进展 在这些情况下，其显着的异质性是限制治疗进展的主要因素。未来 干预措施必须通过更好地了解这些领域的表型和内型来提供信息 更好地设计临床试验的条件。拟建的 ARDS 大湖临床中心 (GLCC)， 肺炎和败血症 (APS) 联盟，由密歇根大学、亨利·福特医院、 辛辛那提大学和芝加哥大学将筛选、注册、收集数据和运输 在这项为期 6 年的 5000 名患者观察研究中，对至少 1000 名患者进行了生物样本。 来自指数住院以及 3、6 和 3 日长期随访的临床信息和生物样本 将收集12个月。生物样本包括血液、粪便、咽拭子和气管内拭子 吸气。标本将被运送到临床协调中心进行储存和未来分析。 我们建议的丰富数据库将为研究人员提供无数的生物学机会 询问 APS 患者的异质性。该数据库中包括研究人员有机会 研究临床疾病轨迹；血液细胞因子、DNA、RNA 和代谢物；胃肠道和 呼吸道微生物群；以及胸部和身体成像。此外，我们提出了两个独特的数据收集 方法：CT 图像的形态测量表征（严格表征身体成分）和 鼻上皮刮除术（研究呼吸道内宿主转录组反应）。 我们还提出了一项针对中心的研究，该研究将阐明微生物组在发育中的作用， ARDS、肺炎和败血症的轨迹和恢复。微生物组是一个重要但不完整的 了解生物异质性的来源，并代表了一个非常有前途的治疗目标。然而我们缺乏 对其在这些条件下的作用的可行理解。我们的团队将利用上述 利用领域领先的方法学专业知识收集样本和数据，以（目标 1）确定途径 哪些肠道和呼吸道微生物群参与脓毒症、急性呼吸窘迫综合征和急性呼吸窘迫综合征的急性发展和轨迹 肺炎和（目标 2）确定肠道微生物群影响的微生物和代谢途径 这些情况后的长期恢复。我们将使用尖端的分子技术来表征 微生物组及其代谢产物，我们将使用复杂的因果推理分析来研究 微生物组在临床结果中的中介作用。通过探究微生物组在 的发展、轨迹和恢复这些条件，该项目将促进发展 微生物组靶向疗法用于预防和治疗。