The American Lung Association (ALA) Lung Health Cohort

项目概要/摘要 肺科医生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稳健方法的发展。 由于缺乏主要关注肺部健康的成人生命过程研究， 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上） 还没有很好的定义。迫切需要确定可改变的风险因素和生物标志物， 肺健康受损，这将使临床医生能够识别肺健康受损，并在慢性 肺部疾病发展。我们将利用美国肺脏协会（ALA）的国家基础设施， Airways临床研究中心（ACRC）成立了第一个全国性的成年人队列，专注于呼吸系统疾病。 健康我们将招募4000名年龄在25-35岁之间的社区居住成年人，他们来自全国17个大都市地区。 美国为了定义肺部健康和制定目标，以在其 最早的阶段我们的长期目标是确定影响未来肺癌风险的成年早期因素， 通过对暴露（环境、社会行为和职业）的详细评估， 反应（生理学、基于成像的和生物学，包括鼻上皮转录组）。在这 初始基线评估，由我们的初步数据提供信息，表明肺健康受损（肺功能降低， 自我报告呼吸道症状，胸部CT扫描显示肺损伤）先于慢性肺发展 疾病，我们将测试几个假设的风险因素和表现受损的肺部健康 通过以下具体目标，在年轻人中：（1）确定是否可改变的暴露和风险 因素（终身空气污染，潜在的有害吸入暴露，如大麻和电子烟， 体力活动减少）与肺功能降低和呼吸道症状加重有关 （2）确定小气道和实质性肺损伤的CT测量是否 与年轻人肺功能降低和呼吸道症状负担增加相关;（3）确定 鼻呼吸道上皮转录组和选定的血液生物标志物之间的关联，CT- 测量了年轻成人的小气道异常和实质性肺损伤。我们将检验 （1）终生暴露于空气污染和其他吸入性暴露（如电子烟和大麻）， 与肺部健康受损相关;（2）新的成像测量与肺部健康受损相关 健康;和（3）呼吸室特异性（鼻上皮转录组）和基于血液的生物标志物 提供对肺部健康受损的生物学基础的深入了解。这些研究将描述 呼吸系统健康和疾病之间的分歧，并提供一个平台，促进健康和 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.