Lung Function Decline and Disease Risk from Young Adulthood to Middle Age

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）是美国第三大死亡原因。虽然吸烟是慢性阻塞性肺病的主要危险因素，但只有少数吸烟者患慢性阻塞性肺病。预测年轻人未来COPD风险的标志物对于降低风险策略和识别亚临床疾病很有价值。虽然COPD的典型定义是阻塞性肺生理学，但许多个体，包括吸烟者，都有肺活量限制生理学。肺功能降低，无论是表现为COPD还是限制，都与不良心血管结局相关。我们的长期目标是确定慢性阻塞性肺病和其他肺部疾病的亚临床表现，并探索心脏和肺部疾病共存的原因。这是一项辅助研究，对年轻人冠状动脉风险发展（CARDIA）队列研究的30年检查。我们将在检查中加入支气管扩张剂前后的肺活量测定，并评估25年以来心脏CT扫描的肺实质和血管结构。根据我们的初步数据，系统性炎症和内皮功能障碍的标志物与年轻人随后的肺功能下降有关，年轻人肺功能下降与高血压事件有关，心脏结构和功能的差异取决于肺功能下降的模式，我们提出以下具体目标：(1)评价青壮年预测COPD发病和/或限制的因素；(2)确定COPD的发生和限制是否与明显的心脏结构和功能改变相关；(3)确定肺结构和胸内血管变化与COPD发病和发病限制的关系。我们将验证系统性炎症和内皮功能障碍的早期生活标志物与随后肺部疾病风险相关的假设，并探讨不同的炎症标志物是否预测不同的肺表型。然后，我们将评估与不同肺表型相关的心脏结构变化，并评估肺结构和肺血管的改变，这些改变可能解释与发展中的肺部疾病相关的并发心血管变化。这些研究将描述肺部疾病的亚临床表现，确定预测未来肺部疾病风险的标志物，并扩大我们对心肺相互作用的理解，因为它们从年轻人的健康发展到中年的疾病。

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. Although smoking is a major risk factor for COPD, only a minority of smokers develops COPD. Markers that predict risk of future COPD in young adults would be valuable to target risk reduction strategies and identify subclinical disease. Although COPD is classically defined by obstructive lung physiology, many individuals, including smokers, have spirometric restrictive physiology. Reduced lung function, whether manifesting as COPD or restriction, is associated with adverse cardiovascular outcomes. Our long-term goals are to identify subclinical manifestations of COPD and other lung disease and explore why heart and lung disease co-exist. This is an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study's year 30 examination. We will add pre- and post-bronchodilator spirometry to the exam and evaluate the lung parenchymal and vascular structure on cardiac CT scans from year 25. Informed by our preliminary data which documents that markers of systemic inflammation and endothelial dysfunction are associated with subsequent lung function decline in young adults, that lung function decline in young adults is associated with incident hypertension, and that there is a divergence in cardiac structure and function depending on the pattern of lung function decline, we propose the following specific aims: (1) To evaluate factors in young adults that predict incident COPD and/or restriction; (2) To determine whether incident COPD and incident restriction are associated with distinct cardiac structural and functional changes; and (3) To determine the lung structural and intrathoracic vascular changes associated with incident COPD and incident restriction. We will test the hypothesis that early life markers of systemic inflammation and endothelial dysfunction are associated with risk of subsequent lung disease and explore whether different inflammatory markers predict different lung phenotypes. We will then evaluate the cardiac structural changes associated with different lung phenotypes and evaluate the lung structural and pulmonary vascular alterations that may explain the concurrently evolving cardiovascular findings associated with developing lung disease. These studies will describe the subclinical manifestations of lung disease, identify markers that predict risk of future lung disease, and expand our understanding of heart-lung interactions as they evolve from health in young adults to disease in middle age.