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.

项目摘要 急性呼吸窘迫综合征（ARDS），肺炎和败血症是威胁生命的疾病 其临床和生物学表现经常是交织的：肺炎是 败血症，两者都是ARDS的诱发条件。尽管已经取得了降低死亡率的进展 这些条件，它们的显着异质性是限制治疗进展的主要因素。未来 必须通过对其中的表型和内型的改进理解来告知干预措施 更好地设计临床试验的条件。拟议的大湖临床中心（GLCC），ARDS， 肺炎和败血症（APS）财团，由密歇根大学，亨利·福特医院组成 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6年期间，对这项5000名患者观察研究的至少1000名患者的生物测量。 指数住院的临床信息和生物测量以及长期随访时3、6和 将收集12个月。生物测量将包括血液，凳子，咽拭子和气管内气管 抽吸。标本将被运送到临床协调中心进行存储和未来分析。 我们提出的富裕数据库将为调查人员提供无数的生物学机会 询问APS患者的异质性。此数据库中包括调查人员的机会 研究临床疾病轨迹；血细胞因子，DNA，RNA和代谢产物；胃肠道和 呼吸微生物群；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图像的形态特征（严格表征身体成分）和 鼻皮脊柱（研究呼吸道内的宿主转录组反应）。 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展中的作用， 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全的 理解的生物异质性来源，代表了一个高度有希望的治疗靶标。但是我们缺乏 对其在这些条件中的作用的可行理解。我们的团队将利用上述 标本和数据收集具有现场领先的方法论专业知识，以（AIM 1）通过 肠道和呼吸菌群参与败血症，ARD和 肺炎和（AIM 2）确定肠道微生物群的微生物和代谢途径 这些条件后的长期恢复。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介导作用。通过询问微生物组在 这些条件的开发，轨迹和恢复，该项目将有助于发展 微生物组靶向预防和治疗的疗法。