Clinical Resource for Lung and Alcohol Investigations

肺和酒精研究的临床资源

• 批准号: 8078579
• 负责人: ELLEN L BURNHAM
• 金额: $ 58.52万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 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/8078579
• 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

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）的常见且严重的医疗状况。尽管在动物模型和小规模的人类研究中进行了许多有趣的观察结果，但旨在降低肺炎患者的发生率的临床试验中，没有一个进步。 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主题。我们将利用该资源来检验以下假设：肺氧化应激，细胞因子环境和内源性蛋白质的改变会导致对肺炎的易感性增加，通过其对肺泡巨噬细胞和支气管气道上皮细胞功能的影响以及对呼吸道微生物组的影响。通过此R24支持，我们将通过从欧盟和LSU的AUDS和匹配的对照中获得其他样本和数据来扩展UCD的既定资源，以及LUMC和UCD的烧伤患者。明尼苏达大学的生物保存专家的支持将为适当的样品处理和存储提供帮助，以确保优质的实验结果。具体目的将包括确定通过对（1）肺泡巨噬细胞肠细胞增多症，凋亡和成熟及其与锌缺乏症和肺氧化应激的关系的影响，使AUDS通过对（1）肺泡巨噬细胞肠细胞增多症，凋亡和成熟及其关系来增加对肺炎的易感性的机制； （2）支气管气道上皮细胞功能，包括Toll样受体-2的表达，纤毛功能以及对在AUD和吸烟的情况下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空间中抗菌蛋白组成/功能改变的关系，以及在存在和没有烧伤的情况下肺/全身细胞因子环境的改变。 相关性：与酒精有关的肺炎是美国的重大医疗保健负担。该领域的研究以前缺乏建立的基础设施来对酒精使用障碍患者进行转化调查的障碍。建立一个联盟来共享与与酒精相关的肺炎研究相关的临床样本和数据，将促进该领域的发现。