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.

项目概要/摘要 个体可以从理想的肺部健康发展到肺部健康受损的中间表型，再发展到 慢性呼吸道疾病，但人们对这种转变知之甚少。这种知识差距的后果是： 缺乏预防慢性肺部疾病的强有力策略。肺部健康队列（LHC）研究（NHLBI）。 5U01HL146408）将在美国各地招募健康参与者，通过以下方式评估他们的肺部健康状况 问卷、生物样本分析、肺活量测定和计算机断层扫描 (CT)，并将这些特征关联起来 在这项辅助研究中，一系列被认为影响肺部健康的拟人化和环境因素。 应用中，我们建议扩展大型强子对撞机的表型分析，以包括肺的详细测量 结构和功能，以获得对可修改风险的影响的更深入的了解 我们假设当前和未来肺部健康的一个关键因素是。 “dysanapsis”，被认为是当气道和肺实质生长不同步时发生的，以致 气道相对于肺的大小而言较小，肥胖儿童的气道衰竭与此相关。 然而，高反应性和哮喘，以及成人慢性阻塞性肺病，需要全面的表征和 尚未评估通过更具体的功能和结构措施对精神崩溃的验证 健康的年轻人也没有被证明是一个纵向风险因素，我们及时和创新的方法将结合起来。 通过 CT 获取结构信息，并对肺活量、肺容量和功能进行最先进的评估 我们勇敢地面对可改变的暴露和影响肺部的风险因素。 通过对气道、实质和肺的结构和功能失调的影响来影响健康 特别是，我们将评估可改变的环境的关联。 除了年龄、性别、种族、BMI之外，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 病史，因为这些因素与气道和血管功能障碍有关， 该提议背后的合理机制假设是： 气道和血管在结构 (CT) 和功能方面与实质不匹配 （PFT）；我们认为这种呼吸失调是早期和进展性肺部疾病的一个无声标志。 研究将利用母体 LHC 研究的基础设施和终点，因为我们将扩展 LHC 以多种重要方式进行调查，以填补决定储备和 肺对疾病的易感性。基线肺功能和心脏和功能的“深度表型分析”。 肺血管结构将提供对可修改暴露的影响的更详细的了解 当前和未来肺部疾病的危险因素。