Understanding airway mucus dysfunction in population-based studies

了解基于人群的研究中的气道粘液功能障碍

• 批准号: 10682508
• 负责人: Alejandro Diaz
• 金额: $ 81.24万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10682508
• 关键词: Adult; Affect; Air; Air Pollution; Airway Disease; Biological; Biology; Bronchitis; Cause of Death; Cells; Chronic; Chronic Bronchitis; Chronic Obstructive Pulmonary Disease; Clinical; Cohort Studies; Coronary Artery Risk Development in Young Adults Study; Coughing; Cross-Sectional Studies; Data; Diameter; Disease; Environmental Epidemiology; Exposure to; Forced expiratory volume function; Framingham Heart Study; Functional disorder; Future; Genetic; Genetic Predisposition to Disease; Hospitalization; Image; Impairment; Individual; Intercept; Logistics; Longevity; Lung; Marijuana; Marijuana Smoking; Mucous body substance; Particulate Matter; Pathologic; Patients; Pattern; Persons; Phenotype; Play; Population; Population Study; Predisposition; Prevalence; Prevention; Prevention strategy; Primary Care; Process; Production; Public Health; Pulmonology; Reporting; Reproducibility; Respiratory Signs and Symptoms; Respiratory System; Risk; Risk Factors; Role; Scanning; Smoker; Smoking; Symptoms; TP53 gene; Testing; Trans-Omics for Precision Medicine; Work; X-Ray Computed Tomography; bronchial mucus; cardiorespiratory fitness; chest computed tomography; chronic respiratory disease; cigarette smoke-induced; clinical care; clinical heterogeneity; clinically relevant; cohort; community living; diagnostic criteria; disorder risk; fitness; follow-up; genetic variant; genome sequencing; genome-wide; imaging detection; insight; longitudinal analysis; lung health; lung imaging; marijuana use; mortality; mucus clearance; mucus hypersecretion; persistent symptom; prevent; protective factors; pulmonary function; rare variant; resilience; treatment strategy; whole genome

Project Summary/Abstract Mucus dysfunction plays a critical role in airway diseases like chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). COPD affects approximately 29 million people in the US and is the third leading cause worldwide. The public health and clinical relevance of “mucus dysfunction” are better understood when one focuses on the clinical manifestations of this process —chronic cough and phlegm and chronic mucus hypersecretion/CB. Up to 32% of community-living individuals report chronic respiratory symptoms and present with normal lung function. The presence of chronic symptoms in these individuals is associated with a substantially increased risk of future hospitalization and mortality. In this proposal, we will use an objective, reproducible assessment of mucus dysfunction. We will identify and score mucus plugging on chest computed tomography (CT) scans from community-living individuals participating in two population-based studies, the Framingham Heart Study (FHS) and Coronary Artery Risk Development in Young Adults (CARDIA). In Aim 1, we will determine the clinical relevance of CT-based mucus plugging. We will evaluate the associations of mucus plugging with lung function, respiratory symptoms, and chronic bronchitis (Aim 1a); and examine whether 5-yr. Persistent CT-based mucus plugging is associated with the decline in FEV1 and future COPD (Aim 1b). In Aim 2, we will examine whether modifiable factors affect CT- based mucus plugging. We will determine whether air pollution and marijuana smoking are associated with increased odds of CT-based mucus plugging and define whether cardiorespiratory fitness is related to decrease mucus plugging. Finally, in Aim 3, we will determine genetic resilience/susceptibility to mucus dysfunction. We will use CT data from the FHS and CARDIA cohorts and genome-wide sequencing data from the TOPMed initiative to identify common and rare variants associated with CT-based mucus plugging. This study will increase our understanding of the clinical implications of an imaging-based mucus dysfunction phenotype at the population level, providing a tangible target for the interception and prevention of chronic airway disease while identifying susceptibility, risk, and protective factors for this process.

项目摘要/摘要 粘液功能障碍在慢性支气管炎（CB）和慢性阻塞性等气道疾病中起关键作用 肺部疾病（COPD）。 COPD在美国影响约2900万人，是第三名 在全球范围内。当“粘液功能障碍”的公共卫生和临床相关性时，可以更好地理解 一个侧重于此过程的临床表现 - 智咳和痰液和慢性粘液 分泌/CB。多达32％的社区生活个人报告了慢性呼吸症状并现在 具有正常的肺功能。这些个体中慢性症状的存在与 大大增加了未来住院和死亡率的风险。 在此提案中，我们将使用对粘液功能障碍的客观，可重复的评估。我们将确定并 在胸部计算机断层扫描（CT）扫描中得分粘液插入社区生活的人 参加两项基于人群的研究，弗雷明汉心脏研究（FHS）和冠状动脉风险 年轻人的发展（Cardia）。在AIM 1中，我们将确定基于CT的粘液的临床相关性 插头。我们将评估粘液堵塞与肺功能，呼吸症状和 慢性支气管炎（AIM 1A）；并检查是否5年。持续的基于CT的粘液插入与 FEV1和未来COPD的下降（AIM 1B）。在AIM 2中，我们将检查可修改因素是否影响CT- 基于粘液塞。我们将确定空气污染和大麻吸烟是否与 基于CT的粘液塞的几率增加，并定义心肺适应性是否与 减少粘液塞。最后，在AIM 3中，我们将确定对粘液的遗传弹性/敏感性 功能障碍。我们将使用来自FHS和Cardia队列的CT数据以及来自基因组的测序数据 最佳计划是确定与基于CT的粘液插入相关的常见和稀有变体。 这项研究将增加我们对基于成像的粘液功能障碍的临床意义的理解 人口水平上的表型，为拦截和预防慢性提供了切实的目标 气道疾病同时确定了此过程的敏感性，风险和受保护因素。