Transitions from Impaired Respiratory Health to Lung Disease

从呼吸系统健康受损到肺部疾病的转变

• 批准号: 10078962
• 负责人: RAVI KALHAN
• 金额: $ 215.07万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10078962
• 关键词: Age; Alveolar; Appearance; Area; Attention; Biological Markers; Blood; Chronic lung disease; Clinical; Communities; Coronary Artery Risk Development in Young Adults Study; Detection; Development; Diagnostic radiologic examination; Disease; Elderly; Enrollment; Epithelial Cells; Evolution; Foundations; Future; Gene Expression; Gene set enrichment analysis; Health; Health Transition; IL8 gene; Image; Impairment; Individual; Inflammation; Inflammatory; Injury; Intercept; Knowledge; Longevity; Longitudinal cohort; Longterm Follow-up; Lung; Lung CAT Scan; Lung diseases; Matrilysin; Measurement; Measures; Modeling; Nasal Epithelium; Nose; Participant; Phenotype; Predisposition; Primary Prevention; Proteins; Proteomics; Public Health; Pulmonary Emphysema; Race; Reporting; Respiratory Signs and Symptoms; Respiratory physiology; Risk; Secretory Cell; Severities; Spirometry; Structure of respiratory epithelium; Supervision; Testing; Thoracic Radiography; Time; Work; X-Ray Computed Tomography; age related; aged; attenuation; base; bronchial epithelium; clinically relevant; cohort; disease phenotype; functional decline; injured; innovation; interstitial; lung injury; member; middle age; novel marker; predictive marker; public health relevance; pulmonary function; pulmonary function decline; receptor for advanced glycation endproducts; resilience; respiratory; respiratory health; secretory protein; sex; surfactant; tool; transcriptome; transcriptome sequencing; whole genome; young adult

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.

项目摘要/摘要 传统上，呼吸界将呼吸健康定义为缺乏肺部疾病。这 定义导致早期肺部疾病被定义为异常呼吸生理学的首次出现， 一个不承认从健康到慢性肺部疾病的过渡会发展的范式 多年来，肺部疾病拦截策略可能是最有效的一段时间。公共卫生 慢性肺疾病的策略重点是疾病拦截授权呼吸受损检测 慢性肺部疾病之前的健康在临床上变得明显。我们的小组调查了预测因素和 年轻人冠状动脉风险发展的肺功能下降的后果（CARDIA） 研究，1985年成立于18-30岁的纵向队列。我们已经确定了呼吸受损的特征 在慢性肺部疾病发展之前的健康。其中包括：年轻的下峰肺功能 成年，与年龄相关的肺功能下降，全身炎症生物标志物的升高和 存在呼吸道症状。虽然我们已经记录了呼吸受损的临床相关性 健康，我们迄今为止的工作并不能为拦截慢性肺部疾病的拦截提供一组目标。我们现在 建议利用Cardia独特的平台研究呼吸健康受损的过渡 致肺病。在Cardia肺研究的此续签应用中，我们将以我们的工作为基础 通过收集肺CT扫描，肺功能和鼻腔，确定肺部健康受损的表型 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 呼吸健康受损的内型。我们将测试成像，血液和鼻生物标志物的假设 用作有用的表型和肺部健康受损的内型，与慢性过渡有关 通过以下特定目的通过以下特定目的：（1）确定多维（整合两个纵向 肺功能和CT肺损伤的度量）生命力轨迹与未来发展相关的轨迹 肺气肿和间质变化，（2）使用蛋白质组学发现平台，确定是否血液 生物标志物预测肺部疾病（肺气肿与间质变化）的分歧表型表现 从呼吸健康受损到肺部疾病的过渡，（3）确定CT肺损伤是否，是否是 肺气肿和间质变化与鼻呼吸道中的基因表达改变有关 上皮。这项研究将调查与易感性相关的因素与对肺部疾病的韧性相关的因素 与肺部健康受损相关的病理生物学变化，并这样做，将为基础做出贡献 对于未来的慢性肺部疾病的拦截。