The American Lung Association (ALA) Lung Health Cohort

项目概要/摘要 肺科医师和呼吸系统研究人员将呼吸系统健康定义为没有肺部疾病。 这种简单化的定义限制了预防肺部疾病的强有力方法的开发。 由于缺乏主要关注肺部健康的成人生命历程研究，中间 肺部健康受损的表型（存在于理想肺部健康和肺部疾病之间的连续体） 尚未被明确定义。迫切需要确定可改变的风险因素和生物标志物 肺部健康受损，这将使临床医生能够识别肺部健康受损并在慢性病发生之前进行干预 出现肺部疾病。我们将利用美国肺脏协会 (ALA) 的国家基础设施 航空公司临床研究中心 (ACRC) 将组建第一个专注于呼吸系统疾病的全国成人队列 健康。我们将从全国17个都市区招募4000名25-35岁的社区成年人 美国旨在定义肺部健康并制定拦截慢性肺部疾病的目标 最早的阶段。我们的长期目标是确定影响未来肺病风险的成年早期因素 通过详细评估暴露（环境、社会行为和职业）和 反应（生理反应、基于成像的反应和生物学反应，包括鼻上皮转录组）。在这个 初步基线评估，根据我们的初步数据表明肺部健康受损（肺功能降低， 呼吸道症状的自我报告、胸部 CT 扫描显示的肺损伤）先于慢性肺病的发展 疾病，我们将测试有关肺部健康受损的危险因素和表现的几种假设 通过以下具体目标对年轻人进行干预： (1) 确定是否可以改变暴露和风险 因素（终生空气污染、潜在有害的吸入暴露，例如大麻和电子烟， 体力活动减少）与肺功能下降和呼吸道症状负担加重有关 在年轻人中； (2) 确定小气道和实质肺损伤的 CT 测量是否正确 与年轻人肺功能较低和呼吸道症状负担加重有关； (3)确定 鼻呼吸道上皮转录组与选定的血液生物标志物、CT- 测量了年轻人的小气道异常和实质肺损伤。我们将测试假设 (1) 终生暴露于空气污染和其他吸入暴露（例如电子烟和大麻） 与肺部健康受损有关； (2) 新颖的成像测量与受损的肺有关 健康； (3) 呼吸区室特异性（鼻上皮转录组）和血液生物标志物 深入了解肺部健康受损的生物学基础。这些研究将描述 呼吸健康与疾病之间的分歧，并为健康促进和疾病提供平台 肺部疾病的一级预防。

Project Summary/Abstract Pulmonary physicians and respiratory researchers define respiratory health as the absence of lung disease. This simplistic definition has limited the development of a robust approach to the prevention of lung disease. Because of the absence of adult life-course studies focused primarily on lung health, the intermediate phenotypes of impaired lung health (which exist on a continuum between ideal lung health and lung disease) have not been well-defined. There is a critical need to identify modifiable risk factors and biomarkers for impaired lung health that will allow clinicians to recognize impaired lung health and intervene before chronic lung disease develops. We will leverage the national infrastructure of the American Lung Association’s (ALA) Airways Clinical Research Centers (ACRC) to form the first national cohort of adults focused on respiratory health. We will recruit 4000 community-dwelling adults aged 25-35 from 17 metropolitan regions across the U.S. for the purpose of defining lung health and developing targets to intercept chronic lung disease at its earliest stages. Our long-term goal is to determine early adulthood factors that influence risk for future lung disease through detailed assessments of exposures (environmental, socio-behavioral, and occupational) and responses (physiologic, imaging-based, and biological including the nasal epithelial transcriptome). In this initial baseline evaluation, informed by our preliminary data indicating impaired lung health (lower lung function, self-report of respiratory symptoms, lung injury on chest CT scan) precedes the development of chronic lung disease, we will test several hypotheses regarding the risk factors and manifestations of impaired lung health in young adults through the following specific aims: (1) Determine whether modifiable exposures and risk factors (lifetime air pollution, potentially noxious inhalational exposures such as marijuana and e-cigarettes, reduced physical activity) are associated with lower lung function and greater burden of respiratory symptoms in young adults; (2) Determine whether CT-measurements of small airway and parenchymal lung injury are associated with lower lung function and greater burden of respiratory symptoms in young adults; (3) Determine the association between the nasal respiratory epithelial transcriptome and selected blood biomarkers, CT- measured small airway abnormality and parenchymal lung injury in young adults. We will test the hypotheses that (1) lifetime exposure to air pollution and other inhalational exposures (e.g. e-cigarettes and marijuana) are associated with impaired lung health; (2) novel imaging measurements are associated with impaired lung health; and (3) respiratory compartment-specific (nasal epithelial transciptome) and blood based biomarkers provide insight into the biologic underpinnings of impaired lung health. These studies will describe the divergence between respiratory health and disease and provide a platform for health promotion and the primary prevention of lung disease.