Administrative Core

行政核心

• 批准号: 10269671
• 负责人: KAREN M RIDGE
• 金额: $ 11.2万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10269671
• 关键词: 2019-nCoV; Acute Lung Injury; Adult Respiratory Distress Syndrome; Advisory Committees; Alveolar; Alveolar Macrophages; Animals; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; COVID-19; Cause of Death; Cell model; Cells; Cessation of life; Clinical; Committee Members; Communication; Development; Disease; Distal; Economics; Enrollment; Epithelial Cells; Etiology; Failure; Feedback; Fostering; Functional disorder; Funding Opportunities; Hospitalization; Human Resources; Hypoxemia; Immune; Immune response; Immunologics; Infection; Inflammation; Influenza A virus; Information Dissemination; Institution; Instruction; Interdisciplinary Study; Link; Lower Respiratory Tract Infection; Lower respiratory tract structure; Lung; Lung Inflammation; Lymphocyte; Organ; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Phase; Play; Pneumonia; Population; Postdoctoral Fellow; Process; Publications; Pulmonary Inflammation; Reagent; Recovery; Research; Research Personnel; Resolution; Resource Sharing; Resources; Respiratory Failure; Role; Sampling; Services; Structure; Structure of parenchyma of lung; Supportive care; Techniques; Testing; Tidal Volume; Tissues; United States; Viral Load result; Viral Pneumonia; Virus; Work; acute hypoxemic respiratory failure; burden of illness; collaborative environment; community acquired pneumonia; economic cost; experimental study; individualized medicine; innovation; lung development; lung injury; lung repair; monocyte; mouse model; neutrophil; novel therapeutic intervention; programs; recruit; repaired; resilience; student mentoring; tissue repair; ventilation

PROJECT SUMMARY_CORE A Recovery from viral pneumonia is a clinically important yet understudied process. Severe viral pneumonia due to influenza A virus (IAV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), damages the lower respiratory tract to cause acute respiratory distress syndrome (ARDS). While acute hypoxemic respiratory failure is a defining clinical feature in patients with ARDS, advances in supportive care allow most patients to survive the hypoxemic phase of their illness. As a result, the vast majority of patients with ARDS die from multiple organ dysfunction, including persistent respiratory failure, days to weeks after the initial infection. Other than avoidance of additional lung injury, via low tidal volume ventilation and a handful of other supportive therapies, there are no specific therapies for patients with viral pneumonia/ARDS. A central hypothesis of this PPG is that the persistence of respiratory failure and the development of multiple organ dysfunction in patients with ARDS is a consequence of the failure of normal mechanisms of inflammation resolution and lung tissue repair. This hypothesis is clinically supported by a recent analysis of patients enrolled in the ARDSnet where a “hyperinflammatory” endotype of ARDS patients was associated with poor clinical outcomes, including death. We propose to investigate the process of recovery from viral pneumonia with a focus on mechanisms that promote resolution of lung inflammation and healthy repair of lung damage. Core A will assist the PPG investigators as they test this central hypothesis of this PPG through a highly integrated and innovative set of experiments by focusing on five Specific Aims: Specific Aim 1. To support communication between the Project Investigators, the Core Leaders, Collaborating investigators, and the Internal and External Advisory Committee members. Specific Aim 2. To provide a structure for the sharing of materials and dissemination of information between the Project Investigators, Core Leaders and their Collaborators. Specific Aim 3. To provide financial and regulatory oversight to the Project and Core Leaders and coordinate their interactions with Institutional Core Services. Specific Aim 4. To disseminate the discoveries made by the program project investigators through publications, presentations and the sharing of resources to other institutions and other investigators. Specific Aim 5. To foster an environment of collaborative interdisciplinary research and mentoring of students, post-doctoral fellows and investigators.

项目概要_核心A 从病毒性肺炎中恢复是一个临床上重要但尚未充分研究的过程。重症病毒性肺炎 甲型流感病毒（IAV）或严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）， 2019冠状病毒病（COVID-19），损害下呼吸道，导致急性呼吸窘迫 综合征（ARDS）。虽然急性低氧性呼吸衰竭是ARDS患者的一个定义性临床特征， 支持性护理的进步使大多数患者能够度过其疾病的低氧血症阶段。结果导致 绝大多数患有ARDS的患者死于多器官功能障碍，包括持续性呼吸衰竭， 在初次感染后的几天到几周内。除了避免额外的肺损伤外，通过低潮气量 虽然目前还没有针对病毒性肺炎患者的特异性治疗方法， 肺炎/ARDS。该PPG的中心假设是呼吸衰竭的持续性和 ARDS患者多器官功能障碍的发展是正常功能衰竭的结果， 炎症消退和肺组织修复的机制。这一假设得到了最近一项临床研究的支持。 对入组ARDSnet的患者进行分析，其中ARDS患者的“高炎症”内源型是 与不良临床结局相关，包括死亡。我们建议调查恢复过程 从病毒性肺炎，重点是机制，促进解决肺部炎症， 肺损伤的健康修复核心A将协助PPG研究者检验这一中心假设， 通过一系列高度集成和创新的实验，专注于五个具体目标： 具体目标1。支持项目研究者、核心领导者、合作者之间的沟通 调查员以及内部和外部咨询委员会成员。 具体目标2。提供一个结构，以便在各机构之间分享材料和传播信息， 项目调查员、核心领导人及其合作者。 具体目标3。为项目和核心领导人提供财务和监管监督，并协调 他们与机构核心服务的互动。 具体目标4。通过出版物传播项目研究人员的发现， 向其他机构和其他调查人员介绍情况和分享资源。 具体目标5.为了培养跨学科合作研究和指导学生的环境， 博士后研究员和调查员。