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 (US) 的第三大死因。 CLRD 最常见的组成部分是慢性阻塞性肺病 (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病情加重，但对病情加重的危险因素了解不够，特别是在老年人、从不吸烟者和少数族裔中。高密度脂蛋白胆固醇 (HDL-c) 和 HDL 亚组分可能有助于 CLRD 发病机制，因为它们在鞘脂调节和运输中发挥作用，而鞘脂调节和运输与哮喘和肺气肿有关。一组研究的初步结果表明，较高水平的 HDL-c 和较大的 HDL 亚组分与较高的 CLRD 事件发生率和更快的肺功能下降有关。 我们建议对五个以老年人为主的 NHLBI 人群进行分析，以测试较高的基线 HDL-c 水平和大的 HDL 亚分数是否与 CLRD 事件发生率增加和肺功能更快的纵向下降相关，而与标准社会人口和临床风险因素无关，而小的 HDL 亚分数将表现出负相关。我们将进一步检查这些关联在种族/族裔、吸烟状况和年龄组定义的阶层中是否相似； CLRD 各组成部分保持一致；与基于 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未来对有 CLRD 事件风险的患者的脂质管理，并建议针对 HDL-鞘脂途径的药物开发目标以预防 CLRD 事件。