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.

项目总结/摘要 个体可以从理想的肺健康发展到肺健康受损的中间表型， 慢性呼吸道疾病，但这种转变知之甚少。这种知识差距的后果是， 缺乏预防慢性肺病的有力策略。肺健康队列（LHC）研究（NHLBI 5 U 01 HL 146408）将招募美国各地的健康参与者，通过以下方式评估他们的肺部健康状况： 问卷调查，生物标本分析，肺活量测定和计算机断层扫描（CT），并将这些特征 一系列被认为影响肺部健康的拟人化和环境因素。在本研究中， 应用，我们建议扩展LHC的表型，包括肺的详细措施， 结构和功能，以便更全面地了解可更改风险的影响 和肺部健康的风险因素。我们假设，当前和未来肺部健康的一个关键方面是 “呼吸困难”，这被认为是当气道和肺实质的不同步生长时发生的， 气道相对于肺的大小较小。儿童呼吸困难与肥胖、呼吸道有关 高反应性和哮喘，以及成人COPD;然而， 通过更具体的功能性和结构性测量来验证吞咽困难尚未在 健康的年轻人也没有被证明是一个纵向风险因素。我们及时创新的方法将联合收割机 通过CT获得的结构信息，以及功能性、最先进的肺量测定、肺容量和 气体交换和气体交换。我们假设可改变的暴露和危险因素影响肺 通过其对气道、实质和肺的结构和功能性消化不良的影响， 脉管系统和气体交换。特别是，我们将评估可改变的环境的关联 烟草、空气污染、大麻和电子烟等因素，以及年龄、性别、种族、BMI， 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， 心脏形态和气体交换。这一提议背后的合理的机械假设是， 在结构（CT）和功能方面，气道和血管与实质不匹配 （PFTs）;我们认为这种消化不良是早期和进行性肺部疾病的无声标志。该辅助 这项研究将利用LHC研究的基础设施和终点，因为我们将扩展LHC 以一些重要的方式进行调查，以填补决定储备和 肺对疾病的易感性。这种基线肺功能和心脏和心功能的“深度表型”， 肺血管结构将提供一个更详细的了解的影响，可修改的曝光 以及当前和未来肺部疾病的风险因素。