Understanding airway mucus dysfunction in population-based studies

项目摘要/摘要 粘液功能障碍在慢性支气管炎(CB)和慢性梗阻等呼吸道疾病中起着关键作用 肺部疾病(COPD)。慢性阻塞性肺病在美国影响着大约2900万人，是第三大 世界范围内的事业。“粘液功能障碍”的公共健康和临床相关性在以下情况下得到更好的理解 一种集中于这一过程的临床表现--慢性咳嗽和慢性粘液。 高分泌/CB。高达32%的社区生活个人报告慢性呼吸道症状和目前 肺功能正常。这些人的慢性症状的出现与 大大增加了未来住院和死亡的风险。 在这项建议中，我们将使用一种客观的、可重复性的粘液功能障碍评估。我们将确定和 社区生活个体胸部CT扫描的粘液堵塞评分 参与两项基于人群的研究，弗雷明翰心脏研究(FHS)和冠状动脉风险 青年发展(CARDIA)。在目标1中，我们将确定基于CT的粘液的临床相关性 堵住了。我们将评估粘液堵塞与肺功能、呼吸道症状和 慢性支气管炎(目标1a)；并检查是否有5年。基于CT的持续性粘液堵塞与 FEV1和未来COPD的下降(目标1b)。在目标2中，我们将研究可修改因素是否影响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恢复能力/易感性 功能障碍。我们将使用来自FHS和CARDIA队列的CT数据以及来自 TOPMed计划识别与CT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。 在人口一级的表型，为拦截和预防慢性病提供了一个切实的目标 在确定这一过程的易感性、风险和保护性因素的同时，对呼吸道疾病进行评估。

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.