HDL cholesterol and chronic lower respiratory disease events in five cohorts

五个队列中的高密度脂蛋白胆固醇和慢性下呼吸道疾病事件

• 批准号: 8735184
• 负责人: R Graham BARR
• 金额: $ 11.76万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8735184
• 关键词: Adult; Allergens; Animal Model; Apolipoproteins; Apoptotic; Asthma; Atherosclerosis; Attenuated; Biological; Bronchitis; Candidate Disease Gene; Cause of Death; Centers for Disease Control and Prevention (U.S.); Ceramides; Cessation of life; Chronic; Chronic Bronchitis; Chronic Obstructive Airway Disease; Data; Development; Elderly; Ethnic Origin; Event; Future; General Population; Genetic Variation; Genotype; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hospitalization; Human; Link; Lipids; Lipoproteins; Literature; Lung; Lung diseases; Minority; Modeling; Morbidity - disease rate; Mus; National Heart, Lung, and Blood Institute; Obstruction; Pathogenesis; Pathway interactions; Patients; Persons; Pulmonary Emphysema; Race; Reflux; Regulation; Resources; Respiratory physiology; Risk; Risk Factors; Role; Sampling; Smoker; Smoking; Smoking History; Smoking Status; Sphingolipids; Spirometry; Stomach; Structure of parenchyma of lung; Symptoms; Testing; United States; Work; World Health Organization; X-Ray Computed Tomography; administrative database; age group; airway inflammation; airway remodeling; base; cigarette smoking; clinical risk; cohort; drug development; follow-up; innovation; mortality; never smoker; non-smoker; novel; particle; population based; prevent; public health relevance; sphingosine 1-phosphate; young adult

DESCRIPTION (provided by applicant): Chronic lower respiratory disease (CLRD) is the 3rd leading cause of death in the United States (US). The most prevalent components of CLRD are chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis and asthma. The primary cause of CLRD mortality and morbidity is exacerbations, yet risk factors for exacerbations are inadequately understood, especially among the elderly, never-smokers and minorities. High density lipoprotein cholesterol (HDL-c) and HDL sub-fractions may contribute to CLRD pathogenesis due to their roles in sphingolipid regulation and transport, which have been implicated in both asthma and emphysema. Preliminary results from one cohort suggest that higher levels of HDL-c and large HDL sub-fractions are associated with higher rates of CLRD events and more rapid decline in lung function. We propose to perform analyses across five NHLBI population-based cohorts of predominantly older adults to test if higher baseline HDL-c levels and large HDL sub-fractions will be associated with increased rates of CLRD events and a more rapid longitudinal decline in lung function independent of standard socio- demographic and clinical risk factors whereas small HDL sub-fractions will demonstrate the inverse associations. We will further examine if these associations are similar across strata defined by race/ethnicity, smoking status and age group; consistent across components of CLRD; and comparable for genetically- estimated HDL-c based on genotype at LIPG rs61755018. Confirmation of these hypotheses would impact future lipid management for patients at risk for CLRD events and suggest targets for drug development on the HDL-sphinoglipid pathway to prevent CLRD events.

描述（由申请人提供）：慢性下呼吸道疾病（CLRD）是美国第三大死亡原因（美国）。 CLRD最普遍的成分是慢性阻塞性肺疾病（COPD），肺气肿，慢性支气管炎和哮喘。 CLRD死亡率和发病率的主要原因是加剧，但对恶化的风险因素不充分，尤其是在老年人，从未吸烟的人和少数群体中。高密度脂蛋白胆固醇（HDL-C）和HDL亚裂缝可能会导致CLRD发病机理，这是由于它们在鞘脂调节和转运中的作用，这与哮喘和肺气肿有关。一个队列的初步结果表明，较高水平的HDL-C和大型HDL子裂缝与较高的CLRD事件发生率和肺功能较快下降有关。 我们建议在五个主要的老年人中进行五个基于NHLBI的人群进行分析，以测试较高的基线HDL-C水平和大型HDL子互动是否与CLRD事件的增加相关，而肺部的纵向下降和更快的纵向下降以及与标准的小型HDL子相关相关的肺部功能更快，而不是标准的社会危险和临床危险因素。我们将进一步研究这些关联是否在种族/种族，吸烟状况和年龄段定义的阶层中是否相似；在CLRD的组成部分之间保持一致；并且基于LIPG rs61755018的基因型遗传估计的HDL-C可比。 这些假设的确认会影响有CLRD事件风险的患者的未来脂质管理，并建议在HDL-Sphinogipid途径上进行药物开发的靶标，以防止CLRD事件。