Patterns of Cardiopulmonary health across the life course

整个生命过程中心肺健康的模式

• 批准号: 10280550
• 负责人: Sadiya Sana Khan
• 金额: $ 78.02万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10280550
• 关键词: Adult; Affect; Age; Age of Onset; Air Pollution; Ancillary Study; Biological Assay; Biological Markers; Biological Process; Cardiac; Cardiac health; Cardiopulmonary; Cardiovascular system; Cause of Death; Chronic lung disease; Clinical; Coronary Artery Risk Development in Young Adults Study; Data; Detection; Disease; EFRAC; Echocardiography; Elderly; Epidemiology; Event; Evolution; Four-dimensional; Functional disorder; Goals; Gold; Health; Health Transition; Heart; Heart Diseases; Heart failure; Image; Impairment; Individual; Inflammation; Inflammatory; Intercept; Intervention; Joints; Left; Left ventricular structure; Life; Life Cycle Stages; Link; Lung; Lung diseases; Magnetic Resonance Imaging; Measures; Mechanics; Mediating; Mediator of activation protein; Morbidity - disease rate; Multimodal Imaging; National Heart, Lung, and Blood Institute; Outcome Study; Participant; Pathway interactions; Pattern; Phenotype; Predisposition; Prevention; Prevention strategy; Proteomics; Public Health; Pulmonary Emphysema; Pulmonary Heart Disease; Pulmonary Hypertension; Race; Research; Respiratory Tract Infections; Risk; Risk Factors; Risk Marker; Scanning; Sex Differences; Spirometry; Structure; Symptoms; Systems Biology; Testing; Time; Tobacco; Tobacco use; United States; Ventricular; Ventricular End-Diastolic Volumes; Viral Respiratory Tract Infection; Vision; Work; X-Ray Computed Tomography; advanced disease; base; blood-based biomarker; clinically relevant; comorbidity; critical period; design; disorder prevention; health care service utilization; hemodynamics; imaging study; lung injury; middle age; mortality; multidisciplinary; novel; phenotypic data; pulmonary function; resilience; risk sharing; screening; tobacco exposure; young adult

ABSTRACT Chronic lung disease and heart failure (HF) are highly prevalent, commonly co-occur, and are associated with significant morbidity and mortality. Work from our group and others has demonstrated an independent relationship between chronic lung disease and incident HF that may be driven in part by inflammation. We have also documented that even in the absence of symptomatic lung disease, impaired lung function defined by spirometry is associated with adverse cardiac remodeling on echocardiography and incident HF events. While symptomatic lung disease and HF often occur in the elderly, many younger adults have relatively asymptomatic impairment in lung health and cardiac structure and function. These subclinical cardiopulmonary abnormalities develop during the key modifiable period from young adulthood to midlife. However, data are sparse on the timing and associated mechanisms of the transition from health to disease spanning young adulthood to midlife, and related race-sex differences. Without identifying these unique patterns of change, it will not be possible to screen for subclinical changes and employ prevention strategies prior to irreversible damage in the lung and heart. This requires upstream identification at the earliest detectable change. While spirometry is the gold standard for lung disease detection, it is a relatively crude and insensitive measure of impaired lung health. In contrast, lung injury (quantified using a novel local histogram analysis developed and validated by our group) from computed tomography (CT) scans is a more sensitive and earlier indicator of impaired lung health (e.g. due to tobacco, air pollution, and respiratory viral infection). Therefore, we now propose to take advantage of the Coronary Artery Risk Development in Young Adults (CARDIA) study’s unique platform to study the temporal relationship of and mechanisms underlying the transition from lung and heart health to disease. To-date, our group has investigated the predictors and consequences of impaired lung health and HF, separately, in CARDIA. In this project, we will build upon our prior work by analyzing CT scans to determine the concurrent evolution of lung injury and adverse cardiac remodeling and identify mechanisms by assaying a multitude of blood-based biomarkers (using a multiplexed array) and performing 4-dimensional flow cardiovascular magnetic resonance imaging (cMRI). We will test the hypothesis that detailed imaging and blood-based markers can inform clinically relevant endotypes reflecting dynamic changes in lung injury and adverse cardiac remodeling during a key vulnerable period of life through the following specific aims: (1) Determine the longitudinal association between lung injury and left ventricular end-diastolic volume (LVEDV); (2) Determine the risk of subclinical and clinical HF among joint lung injury and LVEDV trajectory groups; and (3) Determine the hemodynamic mediators of the association between lung injury and adverse cardiac remodeling. This study will investigate factors associated with transitions from cardiopulmonary health to disease and associated mechanisms, and in doing so, will identify screening strategies and contribute novel pathways for targeted disease interception of lung and heart disease.

摘要 慢性肺部疾病和心力衰竭（HF）非常普遍，通常同时发生，并且与 严重的发病率和死亡率。我们小组和其他人的工作表明， 慢性肺部疾病和HF事件之间的关系可能部分由炎症驱动。我们有 还证明，即使在没有症状性肺病的情况下， 肺量测定与超声心动图上的不良心脏重构和偶发HF事件相关。而 有症状的肺部疾病和HF常发生在老年人中，许多年轻人相对无症状 肺健康和心脏结构和功能受损。这些亚临床心肺异常 在从青年到中年的关键可改变时期发展。然而，数据稀少， 从青年到中年从健康向疾病过渡的时间和相关机制， 以及相关的种族性别差异。如果不确定这些独特的变化模式，就不可能 筛查亚临床变化，并在肺发生不可逆损伤之前采取预防策略， 心这需要在最早可检测到的变化时进行上游识别。虽然肺量测定法是 作为肺部疾病检测的标准，它是一种相对粗糙和不敏感的肺部健康受损的衡量标准。在 相反，肺损伤（使用我们小组开发和验证的新型局部直方图分析进行量化） 从计算机断层扫描（CT）扫描是一个更敏感和更早的指标受损的肺健康（如由于 烟草、空气污染和呼吸道病毒感染）。因此，我们现建议利用 年轻人冠状动脉风险发展（CARDIA）研究的独特平台， 从肺和心脏健康到疾病转变的关系和机制。迄今为止，我们的 该小组在CARDIA中分别研究了肺部健康受损和HF的预测因素和后果。 在本项目中，我们将在之前工作的基础上，通过分析CT扫描来确定 肺损伤和不利的心脏重塑，并确定机制，通过分析大量的血液为基础的 生物标志物（使用多路复用阵列）和进行四维流动心血管磁共振 成像（cMRI）。我们将测试详细的成像和血液标记物可以告知临床的假设 反映肺损伤和心脏重构的动态变化的相关内皮型， 通过以下具体目标确定生命脆弱期：（1）确定 肺损伤和左心室舒张末期容积（LVEDV）;（2）确定亚临床和临床HF的风险 联合肺损伤组和LVEDV轨迹组之间的血流动力学介质;（3）确定 肺损伤与不良心脏重塑之间的相关性。本研究将调查与 从心肺健康到疾病的转变及其相关机制，并在此过程中，将识别 筛选策略，并为肺部和心脏病的靶向疾病拦截提供新的途径。