Understanding airway mucus dysfunction in population-based studies

项目总结/摘要 粘液功能障碍在气道疾病如慢性支气管炎（CB）和慢性阻塞性肺疾病中起关键作用。 肺疾病（COPD）。COPD影响美国约2900万人，是美国第三大慢性阻塞性肺病。 因为全世界。在以下情况下，更好地理解“粘液功能障碍”的公共卫生和临床相关性： 一种侧重于该过程的临床表现-慢性咳嗽和痰以及慢性粘液 分泌过多/CB。高达32%的社区生活者报告有慢性呼吸道症状， 肺功能正常这些人的慢性症状的存在与 大大增加了未来住院和死亡的风险。 在这个建议中，我们将使用一个客观的，可重复的评估粘液功能障碍。我们将查明和 对社区生活个体的胸部计算机断层扫描（CT）上的粘液堵塞进行评分 参与了两项基于人群的研究，即FHS和冠状动脉风险研究。 青年发展（Cardia）。在目标1中，我们将确定基于CT的粘液 堵塞我们将评估粘液阻塞与肺功能、呼吸道症状和 慢性支气管炎（目标1a）;并检查是否5年。持续性CT粘液堵塞与 FEV 1下降和未来COPD（目标1b）。在目标2中，我们将研究是否可修改的因素影响CT- 基于粘液堵塞。我们将确定空气污染和吸食大麻是否与 增加基于CT的粘液堵塞的几率，并确定心肺功能是否与 减少粘液堵塞。最后，在目标3中，我们将确定对粘液的遗传弹性/易感性 功能障碍我们将使用来自FHS和CARDIA队列的CT数据和来自FHS和CARDIA队列的全基因组测序数据。 TOPMed倡议，以确定与CT为基础的粘液堵塞相关的常见和罕见变异。 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 表型，为拦截和预防慢性 呼吸道疾病，同时确定这一过程的易感性，风险和保护因素。

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.