Functional Measures of Lung Health in Chronic Ethanol Drinking for Understanding SARS-CoV-2 Infection and Treatment

长期饮酒时肺部健康的功能测量，以了解 SARS-CoV-2 感染和治疗

• 批准号: 10198427
• 负责人: Erich Baker
• 金额: $ 5.89万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10198427
• 关键词: 2019-nCoV; Acute; Address; Adult Respiratory Distress Syndrome; Alcohol consumption; Alcohols; Alveolar; Alveolar Macrophages; Animals; Aspirate substance; Autopsy; Biomedical Research; Blood; Brain; Bronchoalveolar Lavage; COVID-19; Cells; Cessation of life; Chronic; Chronic Phase; Clinical; Clinical Chemistry; Communities; Complex; Coronavirus; Coughing; Data; Defect; Development; Disease; Disease Outbreaks; Dose; Dyspnea; Epithelial Cells; Ethanol; Failure; Fatigue; Female; Fever; Functional Residual Capacity; Functional disorder; Funding; Gases; Grant; Health; Heart; Heavy Drinking; Histologic; Image; Immune; Immune response; Immune system; Immunity; Immunologics; Impairment; Individual; Infection; Inflammatory; Innate Immune System; Interleukin-6; Irrigation; Knowledge; Lead; Liquid substance; Liver; Longitudinal Studies; Lung; Lung Capacity; Lung Inflammation; Lung diseases; Lung infections; Macaca mulatta; Measurement; Measures; Mechanics; Mediator of activation protein; Microbe; Middle East Respiratory Syndrome Coronavirus; Modeling; Molecular; Monkeys; Monoclonal Antibody R24; Morbidity - disease rate; Myeloid Cells; Neutrophil Infiltration; Outcome; Oxidative Stress; Oxygen; Parents; Pathogenesis; Pathology; Patients; Phagocytosis; Phase; Physiological; Physiology; Pneumonia; Population; Predisposition; Primates; Process; Production; Protocols documentation; Research; Research Personnel; Resources; Respiratory Failure; Respiratory physiology; Risk Factors; Role; SARS coronavirus; Sales; Sampling; Self Administration; Severities; Sputum; Standardization; Structure of parenchyma of lung; Study Subject; TNF gene; Testing; Time; Tissue Banks; Tissues; Viral; Viral Respiratory Tract Infection; Virus Diseases; X-Ray Computed Tomography; adverse outcome; alcohol effect; alcohol exposure; alcohol use disorder; alveolar epithelium; bone; chemokine; chronic alcohol ingestion; clinical diagnostics; co-infection; comorbidity; coronavirus disease; cytokine; cytokine release syndrome; data modeling; drinking; human subject; immune system function; lung preservation; macrophage; male; monocyte; pandemic disease; response; social; tissue repair

PROJECT SUMMARY SARS-CoV-2, the causative agent of COVID-19, is responsible for a continuing pandemic with over 2 million infected individuals and 115,000 deaths in the US as of June 11, 2020 with cases still rising. Similar to the respiratory diseases caused by the SARS and MERS coronaviruses, COVID-19 is characterized by fatigue, cough, fever, sputum production, dyspnea, and acute respiratory distress syndrome (ARDS). ARDS is the result of excessive lung inflammation causing the accumulation of fluid and inflammatory cell debris and leading to decreased gas exchange and oxygen levels, and eventual multi-organ failure. The leading hypothesis for the molecular basis of SARS-CoV-2 pathogenesis is that an aberrant induction of pro- inflammatory cytokines, chemokines and soluble mediators lead to a debilitating cytokine storm that in turn results in severe lung tissue damage (3-6). Current studies suggest a major role for myeloid cell subsets in the development of the cytokine storm, but the precise roles of pro-inflammatory alveolar monocytes and macrophages have not been thoroughly examined and animal or human subject studies. SARS-CoV-2 disruption to daily routines and social settings have led to increased sales and consumption of alcoholic beverages. As chronic heavy alcohol consumption compromises lung health and immunity leading to increased susceptibility to both bacterial and viral pulmonary infections, and is a risk factor for ARDS. Thus, chronic heavy alcohol drinking could increase the chances of COVID-19 infection and exacerbate the disease course. However, there are no longitudinal studies in controlled populations that provide both precise measures of lung function with exact measures of alcohol consumption in human subjects. In this proposal we will obtain a pulmonary functional test (PFT), a clinical diagnostic of lung infection (CT) and alveolar macrophages to the R24 AA01943 Monkey Alcohol Tissue Research Resource (MATRR). This added capacity will be a resource for investigators to understand 19 the potentially complex relationships between alcohol consumption and COVID- related-outcomes and to enhance the nation's response to the current pandemic.

项目总结 新冠肺炎的病原体SARS-CoV-2导致了持续的大流行，有200多万人 截至2020年6月11日，美国有11.5万名感染者和11.5万人死亡，病例仍在上升。类似于 由SARS和MERS冠状病毒引起的呼吸道疾病，新冠肺炎的特点是疲劳， 咳嗽、发烧、咳痰、呼吸困难和急性呼吸窘迫综合征(ARDS)。ARDS是 过度的肺部炎症导致积聚液体和炎性细胞碎片 导致气体交换和氧气水平下降，最终导致多器官衰竭。领先者 SARS-CoV-2致病机制的分子基础假说是异常诱导前病毒感染。 炎性细胞因子、趋化因子和可溶性介质导致一场衰弱的细胞因子风暴，进而 导致严重的肺组织损伤(3-6例)。目前的研究表明，髓系细胞亚群在急性髓系白血病中起着重要作用。 细胞因子风暴的发展，但促炎症的肺泡单核细胞和 巨噬细胞还没有得到彻底的检查，也没有进行动物或人类的研究。SARS-CoV-2 对日常生活和社交环境的破坏导致酗酒者的销售和消费增加 饮料。由于长期大量饮酒损害肺部健康和免疫力，导致 对细菌和病毒肺部感染的易感性，是ARDS的风险因素。因此，慢性 大量饮酒可能会增加感染新冠肺炎的几率，并加剧病程。 然而，没有在对照人群中进行的纵向研究，既能提供精确的肺测量，也能提供肺的精确测量。 准确测量受试者的酒精消耗量。在此提案中，我们将获得一个 肺功能试验(PFT)是一种临床诊断肺部感染(CT)和肺泡巨噬细胞的方法 R24 AA01943猴酒精组织研究资源(MATRR)。这一增加的容量将是一种资源 让调查人员了解 19 酒精消费和新冠肺炎之间潜在的复杂关系- 这是一项重要的成果，并加强了该国对当前大流行病的反应。