Transitions from Impaired Respiratory Health to Lung Disease

项目摘要/摘要 呼吸系统社区传统上将呼吸健康定义为没有肺部疾病。这 定义导致早期肺部疾病被定义为呼吸生理异常的第一次出现， 一种不承认从健康到慢性肺病的转变已经结束的范式 几年，在一段时间内，肺部疾病的拦截策略可能是最有效的。一种公共卫生 以疾病拦截为重点的慢性肺病战略要求检测呼吸受损 在慢性肺部疾病变得临床明显之前的健康。我们的小组已经调查了预测因素和 肺功能下降对青年冠状动脉风险发展的影响(CARDIA) 这项研究是1985年开始时的纵向队列，年龄在18-30岁。我们已经确定了呼吸受损的特征 在慢性肺病发生之前的健康状况。这些包括：年轻人肺功能峰值较低 成年期，与年龄相关的肺功能下降加速，全身炎症生物标记物的升高，以及 呼吸道症状的存在。虽然我们已经记录了呼吸受损的临床相关性 在卫生方面，我们的工作到目前为止还没有为拦截慢性肺部疾病提供一套目标。我们现在 建议利用CARDIA的独特平台研究呼吸健康受损的过渡 与肺病有关。在这项对心肺研究的续期申请中，我们将在我们已经完成的工作的基础上再接再厉 通过收集肺CT扫描、肺功能和鼻腔扫描来确定肺健康受损的表型 在CARDIA 35年检查中的上皮基因表达。我们将寻求验证表型并确定 呼吸系统健康受损的内分泌类型。我们将检验成像、血液和鼻腔生物标记物 作为肺健康受损的有用的表型和内型，并与向慢性 肺病通过以下具体目标：(1)确定多维(纵向结合 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 肺气肿和间质改变，(2)使用蛋白质组发现平台，确定血液是否 生物标志物预测肺部疾病(肺气肿与间质改变)的不同表型表现 从呼吸健康受损到肺部疾病的转变，(3)确定CT肺损伤， 鼻腔呼吸道基因表达改变与肺气肿和间质改变相关 上皮组织。这项研究将调查与肺部疾病易感性和恢复力相关的因素 与肺健康受损相关的病理生物学变化，在这样做的过程中，将有助于 为将来拦截慢性肺病做准备。

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.