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。CLRD最常见的组成部分是慢性阻塞性肺疾病（COPD）、肺气肿、慢性支气管炎和哮喘。慢性阻塞性肺病死亡率和发病率的主要原因是病情恶化，但对病情恶化的危险因素了解尚不充分，特别是在老年人、不吸烟者和少数民族中。高密度脂蛋白胆固醇（HDL-c）和HDL亚组分可能参与CLRD的发病机制，因为它们在鞘脂调节和运输中起作用，这在哮喘和肺气肿中都有牵连。一个队列的初步结果表明，较高水平的HDL-c和较大的HDL亚组分与较高的CLRD发生率和更快的肺功能下降有关。我们建议对5个以老年人为主的NHLBI人群队列进行分析，以测试是否较高的基线HDL-c水平和较大的HDL亚分数与CLRD事件发生率增加和肺功能更快的纵向下降相关，而独立于标准的社会人口统计学和临床危险因素，而较小的HDL亚分数将显示出相反的关联。我们将进一步研究这些关联是否在由种族/民族、吸烟状况和年龄组界定的各个阶层中相似；CLRD各组成部分的一致性；并且基于LIPG rs61755018基因型的遗传估计HDL-c具有可比性。这些假设的证实将影响有CLRD事件风险的患者未来的脂质管理，并为高密度脂蛋白-鞘脂途径的药物开发提供靶点，以预防CLRD事件。