Clinical Resource for Lung and Alcohol Investigations

肺和酒精研究的临床资源

基本信息

批准号：
8308358
负责人：
ELLEN L BURNHAM
金额：
$ 58.8万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8308358
关键词：
Academic Medical Centers Accounting Affect Age Alcohols Alveolar Alveolar Macrophages Animal Model Apoptosis Bacterial Pneumonia Basic Science Burn injury Cause of Death Cell physiology Cessation of life Cirrhosis Clinical Clinical Investigator Clinical Trials Collaborations Colorado Commit Communicable Diseases Complement Country Data Defect Dependence Disease Ecology Ensure Environment Epithelial Cells Functional disorder Health Healthcare Healthcare Systems Homeostasis Hospitalization Host Defense Human Incidence Individual Infection Influenza Institution Intervention Investigation Lead Liver diseases Louisiana Lung Lung diseases Mediator of activation protein Medical Minnesota Modeling Modification Monoclonal Antibody R24 Mus Nebraska Operative Surgical Procedures Outcome Oxidative Stress Pancreatitis Patients Pneumonia Postoperative Period Predisposition Principal Investigator Process Proteins Protocols documentation Recording of previous events Recruitment Activity Research Research Design Research Infrastructure Research Personnel Resources Respiratory System Respiratory tract structure Risk Sample Size Sampling Scientist Secure Severities Site Smoke Smoking Stratification T-Lymphocyte Testing Toll-Like Receptor 2 Traffic accidents Translations Trauma United States National Institutes of Health Universities Ventilator Zinc deficiency adduct alcohol research alcohol use disorder animal model development antimicrobial base care burden cell motility cigarette smoking cost cytokine human subject injured innate immune function innovation microbial microbicide microbiome mortality response therapy development

项目摘要

DESCRIPTION (provided by applicant): Pneumonia is a common and serious medical condition among individuals with alcohol use disorders (AUDs) in the US. Despite numerous intriguing observations in animal models and small scale human investigations, none have progressed forward into clinical trials aimed at decreasing the incidence of pneumonia in those with AUDs. To promote innovation in the field, investigators at the University of Colorado Denver (UCD) are seeking support to lead a consortium comprised of 4 premier sites in alcohol- related pneumonia research, including Emory University (EU), Louisiana State University (LSU), Loyola University (LUMC), and the University of Nebraska (UNMC) to investigate the effect of AUDs on susceptibility for pneumonia in human subjects. We will utilize this resource to test the hypothesis that alcohol-related alterations on pulmonary oxidative stress, the cytokine milieu, and endogenous proteins lead to an increased susceptibility to pneumonia through their influence on alveolar macrophage and bronchial airway epithelial cell function, and their influence on the respiratory tract microbiome. With this R24 support, we will expand an established resource at UCD by obtaining additional samples and data from subjects with AUDs and matched controls from EU and LSU, and from burned patients at LUMC and UCD. Support from biopreservation experts at the University of Minnesota will provide assistance in appropriate sample processing and storage to ensure quality experimental results. Specific aims will include determining the mechanisms whereby AUDs increase the predisposition to pneumonia via effects on (1)alveolar macrophage enterocytosis, apoptosis, and maturation and their relationship to zinc deficiency and pulmonary oxidative stress; (2)bronchial airway epithelial cell function, including expression of toll-like receptor-2, ciliary function, and response to protein adducts formed in the setting of AUDs and smoking; (3)respiratory tract microbial ecology, and its relationship to alterations in antimicrobial protein composition/function in the alveolar space, and alterations in pulmonary/systemic cytokine milieu in the presence and absence of burn injury. RELEVANCE: Alcohol-related pneumonias are a significant health care burden to the US. Research in this field has been hampered previously by the lack of an established infrastructure to conduct translational investigations in individuals with alcohol use disorders. Creating a consortium to share clinical samples and data relevant to the study of alcohol-associated pneumonias with committed investigators will promote discovery in this field.

描述（由申请人提供）：肺炎是美国酒精使用障碍 (AUD) 患者中常见且严重的疾病。尽管在动物模型和小规模人体研究中进行了大量有趣的观察，但没有一项研究进展到旨在降低 AUD 患者肺炎发病率的临床试验。为了促进该领域的创新，科罗拉多大学丹佛分校 (UCD) 的研究人员正在寻求支持，以领导一个由 4 个酒精相关性肺炎研究顶级机构组成的联盟，其中包括埃默里大学 (EU)、路易斯安那州立大学 (LSU)、洛约拉大学 (LUMC) 和内布拉斯加大学 (UNMC) 合作研究 AUD 对人类受试者肺炎易感性的影响。我们将利用该资源来检验以下假设：酒精相关的肺氧化应激、细胞因子环境和内源性蛋白质的改变通过影响肺泡巨噬细胞和支气管气道上皮细胞功能以及对肺炎的影响而导致肺炎易感性增加。呼吸道微生物组。借助 R24 的支持，我们将通过从 EU 和 LSU 的 AUD 受试者和匹配对照以及 LUMC 和 UCD 的烧伤患者获取更多样本和数据来扩展 UCD 的现有资源。明尼苏达大学生物保存专家的支持将在适当的样品处理和储存方面提供帮助，以确保实验结果的质量。具体目标包括确定 AUD 通过影响 (1) 肺泡巨噬细胞肠细胞作用、凋亡和成熟而增加肺炎易感性的机制及其与缺锌和肺氧化应激的关系； (2)支气管气道上皮细胞功能，包括Toll样受体2的表达、纤毛功能以及对AUD和吸烟环境中形成的蛋白质加合物的反应； (3)呼吸道微生物生态学，及其与肺泡腔抗菌蛋白组成/功能变化的关系，以及烧伤存在和不存在时肺/全身细胞因子环境的变化。相关性：酒精相关肺炎对美国来说是一个重大的医疗负担。此前，由于缺乏对酒精使用障碍患者进行转化研究的基础设施，该领域的研究一直受到阻碍。创建一个联盟，与忠诚的研究人员共享与酒精相关性肺炎研究相关的临床样本和数据，将促进该领域的发现。