Deep Functional Phenotyping of the ALA Lung Health Cohort

ALA 肺部健康队列的深层功能表型分析

• 批准号: 10685503
• 负责人: Charles G Irvin
• 金额: $ 69.14万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685503
• 关键词: Adult; Age; Air Pollution; Allergic rhinitis; Ancillary Study; Asthma; Blood Vessels; Body mass index; COVID-19; Carbon Monoxide; Cardiac; Child; Childhood Asthma; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Cohort Studies; Communities; Data; Diffusion; Disease; Disease Progression; Electronic cigarette; Environmental Risk Factor; Ethnic Origin; Exercise; Funding; Future; Gases; Goals; Growth; Heart; Heart Atrium; Impairment; Individual; Infrastructure; Investigation; Knowledge; Left; Left Ventricular Mass; Link; Longitudinal cohort; Lung; Lung Capacity; Lung diseases; Marijuana; Measures; Morphology; National Heart, Lung, and Blood Institute; Nature; Obesity; Oscillometry; Oxygen; Oxygen saturation measurement; Parents; Participant; Pathogenesis; Persons; Phenotype; Predisposition; Prevention strategy; Public Health; Pulmonary Function Test/Forced Expiratory Volume 1; Questionnaires; Recording of previous events; Respiratory Signs and Symptoms; Risk Factors; Role; Smoker; Spirometry; Structure; Structure of parenchyma of lung; Tobacco; Validation; Walking; X-Ray Computed Tomography; airway hyperresponsiveness; chronic respiratory disease; cohort; heart dimension/size; injured airway; innovation; insight; lung health; lung volume; premature; prevent; pulmonary function; recruit; sex; young adult

Project Summary/Abstract An individual can progress from ideal lung health, to an intermediate phenotype of impaired lung health, to chronic respiratory disease, yet this transition is poorly understood. A consequence of this knowledge gap is the lack of robust strategies to prevent chronic lung disease. The Lung Health Cohort (LHC) study (NHLBI 5U01HL146408) will recruit healthy participants across the US to have their lung health evaluated through questionnaires, biospecimen analysis, spirometry, and computerized tomography (CT), and relate these features to an array of anthropomorphic and environmental factors thought to influence lung health. In this Ancillary study application, we propose to extend the phenotyping of the LHC to include detailed measures of lung structure and function to obtain a more robust understanding of the influence of modifiable exposures and risk factors on lung health. We postulate that a key aspect of both current and future lung health is “dysanapsis”, which is thought to occur when dyssynchronous growth of airways and lung parenchyma such that the airways are small relative to lung size. Dysanapsis has been associated in children with obesity, airways hyperresponsiveness and asthma, and in adults, with COPD; however, a comprehensive characterization and validation of dysanapsis by both more specific functional and structural measures has not been assessed in healthy young adults nor shown to be a longitudinal risk factor. Our timely and innovative approach will combine structural information by CT with functional, state-of the-art assessment of spirometry, lung volumes, and oscillometry and gas exchange. We hypothesize that modifiable exposures and risk factors influence lung health by their effects on structural and functional dysanapsis of the airway, parenchyma and pulmonary vasculature and gas exchange. In particular, we will assess the associations of modifiable environmental factors such as tobacco, air pollution, marijuana and electronic cigarettes, in addition to age, sex, ethnicity, BMI, prematurity, allergic rhinitis, and history of COVID-19, as these factors relate to airway and vascular dysanapsis, cardiac morphology and gas exchange. The plausible mechanistic hypothesis that underlies the proposal is that there is mismatching of airways and blood vessels to parenchyma both in terms of structure (CT) and function (PFTs); we posit that this dysanapsis is a silent marker of early and progressive lung disease. This ancillary study will leverage the infrastructure and endpoints of the parent LHC study, as we will extend the LHC investigation in a number of significant ways to fill knowledge gaps that determine both the reserve and susceptibility of the lung to disease. This “deep phenotyping” of the baseline lung function and cardiac and pulmonary vascular structure will provide a more detailed understanding of the influence of modifiable exposures and risk factors of both current and future lung disease.

项目摘要/摘要 一个人可以从理想的肺部健康发展到肺部健康受损的中间表型，再到 慢性呼吸道疾病，但这种过渡尚未理解。知识差距的结果是 缺乏预防慢性肺部疾病的强大策略。肺部健康队列（LHC）研究（NHLBI） 5U01HL146408）将招募美国各地的健康参与者，以通过 问卷，生物循环分析，肺活量法和计算机断层扫描（CT），以及这些功能 一系列被认为会影响肺部健康的拟人化和环境因素。在这项辅助研究中 应用，我们建议将LHC的表型扩展到包括肺的详细指标 结构和功能，以获得对可修改暴露影响的更强有力的理解 和肺部健康的危险因素。我们假设当前和未来肺部健康的关键方面是 “ dysanapsis”，这被认为是在气道和肺实质的异步生长时发生的 气道相对于肺大小很小。肥胖症儿童，气道有关联 反应性和哮喘，以及成年人和COPD；但是，全面的特征和 尚未评估通过更具体的功能和结构测量对dysanaps的验证 健康的年轻人也不是纵向风险因素。我们及时，创新的方法将结合起来 CT通过功能性的，最新的肺活量测定法和肺部体积和最新评估的结构信息 振荡和气体交换。我们假设可修改的暴露和危险因素会影响肺 健康对气道，实质和肺的结构和功能性障碍的影响 脉管系统和天然气交换。特别是，我们将评估可修改环境的关联 除了年龄，性别，种族，BMI，烟草，空气污染，大麻和电子烟等因素 早产，过敏性鼻炎和Covid-19的史，因为这些因素与气道和血管dysanapsis有关， 心脏形态和气体交换。提出的基础的合理机理假设是 在结构（CT）和功能方面，气道和血管都与实质不匹配 （PFTS）;我们认为这种障碍是早期和进行性肺部疾病的无声标记。这个辅助 研究将利用父LHC研究的基础设施和终点，因为我们将扩展LHC 通过多种重要方式调查确定储量和储备的知识空白 肺对疾病的敏感性。基线肺功能和心脏和心脏的“深度表型”以及 肺血管结构将对可修改暴露的影响提供更详细的理解 以及当前和未来肺部疾病的危险因素。