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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要 SARS-CoV-2 是 COVID-19 的病原体，造成了超过 200 万人的持续大流行截至 2020 年 6 月 11 日，美国已有 115,000 人感染，死亡人数仍在上升。类似于由 SARS 和 MERS 冠状病毒引起的呼吸道疾病，COVID-19 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 是过度肺部炎症导致液体和炎症细胞碎片积聚的结果导致气体交换和氧气水平下降，最终导致多器官衰竭。领先的 SARS-CoV-2 发病机制的分子基础假说是，前体细胞的异常诱导炎症细胞因子、趋化因子和可溶性介质会导致细胞因子风暴，从而使人衰弱导致严重的肺组织损伤 (3-6)。目前的研究表明骨髓细胞亚群在细胞因子风暴的发展，但促炎性肺泡单核细胞的确切作用和巨噬细胞尚未经过彻底检查和动物或人类受试者研究。 SARS-CoV-2 日常生活和社交环境的中断导致酒精饮料的销售和消费增加饮料。由于长期大量饮酒会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 的危险因素。因此，慢性大量饮酒可能会增加感染 COVID-19 的机会并加剧病程。然而，目前还没有针对受控人群的纵向研究提供肺功能的精确测量。具有精确测量人类受试者饮酒量的功能。在这个提案中我们将获得肺功能测试（PFT），肺部感染（CT）和肺泡巨噬细胞的临床诊断 R24 AA01943 猴子酒精组织研究资源 (MATRR)。增加的容量将成为一种资源以便调查人员了解 19 号饮酒与新冠病毒之间潜在的复杂关系相关成果并加强国家对当前大流行病的反应。