Transitions from Impaired Respiratory Health to Lung Disease

项目总结/摘要 呼吸系统社区传统上将呼吸系统健康定义为没有肺部疾病。这 定义导致早期肺病被定义为异常呼吸生理学的首次出现， 一种范式，不承认从健康到慢性肺病的转变， 这段时间是肺部疾病拦截策略可能最有效的时期。一个公共卫生 针对慢性肺病的战略侧重于疾病拦截，要求检测呼吸道受损 在慢性肺病临床表现出来之前，我们的小组已经调查了预测因素， 肺功能下降在年轻人冠状动脉风险发展中的后果（CARDIA） 这项研究是1985年开始的一项18-30岁的纵向队列研究。我们已经发现了呼吸系统受损的特征 在慢性肺病发展之前健康状况。这些包括：年轻人的肺功能峰值较低 成年期，年龄相关的肺功能加速下降，全身炎症生物标志物升高，以及 出现呼吸道症状。虽然我们已经记录了呼吸道损害的临床相关性， 在健康方面，我们至今的工作并没有提供一套目标，以堵截慢性肺病。我们现在 我建议利用CARDIA的独特平台，研究从呼吸系统健康受损到 肺部疾病。在此次CARDIA Lung研究的更新申请中，我们将以我们的工作为基础， 通过收集肺部CT扫描、肺功能和鼻功能， CARDIA 35年检查时的上皮基因表达。我们将寻求验证表型， 呼吸道健康受损的内在型。我们将检验影像学、血液和鼻腔生物标志物 作为肺健康受损的有用表型和内型， 肺疾病通过以下具体目标：（1）确定多维（整合两个纵向 肺功能和CT肺损伤的测量）与未来发展相关的生命过程轨迹， 肺气肿和间质变化，（2）使用蛋白质组学发现平台，确定血液是否 生物标志物预测肺疾病的不同表型表现（肺气肿与间质性变化）， 从受损的呼吸健康到肺部疾病的转变，（3）确定CT是否肺损伤， 肺气肿和间质性改变与鼻呼吸道基因表达改变有关， 上皮这项研究将调查与肺部疾病易感性和恢复力相关的因素， 与肺部健康受损相关的病理生物学变化，这样做，将有助于建立一个基础， 用于将来拦截慢性肺病。

Project Summary/Abstract The respiratory community has traditionally defined respiratory health as the absence of lung disease. This definition results in early lung disease being defined as the first appearance of abnormal respiratory physiology, a paradigm that does not acknowledge that the transition from health to chronic lung disease develops over years, a period of time when lung disease interception strategies could be most efficacious. A public health strategy for chronic lung disease focused on disease interception mandates the detection of impaired respiratory health before chronic lung disease becomes clinically apparent. Our group has investigated the predictors and consequences of lung function decline in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal cohort aged 18-30 at inception in 1985. We have identified features of impaired respiratory health that precede the development of chronic lung disease. These include: lower peak lung function in young adulthood, accelerated age-related decline in lung function, elevations in systemic inflammatory biomarkers, and the presence of respiratory symptoms. While we have documented the clinical relevance of impaired respiratory health, our work to-date does not provide a set of targets for the interception of chronic lung disease. We now propose to take advantage of CARDIA's unique platform to study the transition from impaired respiratory health to lung disease. In this renewal application to the CARDIA Lung study, we will build upon our work which has determined phenotypes of impaired lung health by collecting lung CT scans, pulmonary function, and nasal epithelial gene expression at the CARDIA year 35 examination. We will seek to validate phenotypes and identify endotypes of impaired respiratory health. We will test the hypothesis that imaging, blood, and nasal biomarkers serve as useful phenotypes and endotypes of impaired lung health and are associated with transitions to chronic lung disease through the following specific aims: (1) Determine multidimensional (integrating both longitudinal measures of lung function and CT lung injury) lifecourse trajectories associated with the future development of emphysema and interstitial change, (2) Using a proteomic discovery-platform, determine whether blood biomarkers predict divergent phenotypic manifestations of lung disease (emphysema vs. interstitial change) in the transition from impaired respiratory health to lung disease, (3) Determine whether CT lung injury, emphysema, and interstitial change are associated with altered gene expression in the nasal respiratory epithelium. This study will investigate factors associated with susceptibility versus resilience to lung disease and the pathobiologic changes associated with impaired lung health, and in doing so, will contribute to a foundation for the future interception of chronic lung disease.