UAB Mentoring Program in COPD Patient Oriented Research

摘要 慢性阻塞性肺病是美国第三大死因，对公众健康有重大影响。当前 治疗可以改善症状，但不能阻止疾病进展或降低死亡率。这在一定程度上 由于包括心血管疾病在内的合并症的高负担，使诊断和治疗变得复杂 治疗。COPD相关的心血管疾病尚未得到充分研究，但可能会提供 改善临床结果的途径。目前还没有针对COPD相关肺病的有效治疗方法 血管疾病，尽管有许多试验测试了严重肺动脉高压患者的血管扩张剂。 由于缺乏一种非侵入性的肺压力测量方法，这些研究的进行受到了阻碍。 而且没有工具能够充分检测到早期的肺血管异常。我们开发了一种新的，非 有创的心脏MRI测量的肺动脉阻抗(速度传递函数)可能证明 有助于识别和量化与COPD相关的肺血管疾病。具体目标1 这项建议的目的是确定速度传递函数是否能识别肺功能异常 慢性阻塞性肺疾病患者的动脉阻抗及其与右心功能的关系它的历史也很悠久。 β-受体阻滞剂可降低心血管疾病患者的死亡率，但COPD患者往往被否认 这些药物是因为担心β-受体阻滞剂对呼吸道功能的不良影响。多重 现在的观察性研究表明，β-受体阻滞剂实际上可以降低COPD和 用于预防COPD恶化的多中心、随机、安慰剂对照的Beta-Blocker(BLOCK- COPD)的试验正在进行中，以验证这一假设。无论结果如何，关于风险的问题仍将存在- β-受体阻滞剂对慢性阻塞性肺疾病患者的益处，包括其对运动的影响。具体目标2 建议通过周期测功法确定美托洛尔对患者高峰运动的影响。 患有慢性阻塞性肺病。这项提议还旨在为新的调查员提供指导和培训机会 开展以患者为中心的COPD研究。指导将量身定做，以满足兴趣和 个别受训人员的目标，但将通过一对一和小组形式介绍一组核心主题 会话。生物统计学方面的专门培训以及定量胸部CT和 还将提供心脏核磁共振检查。学员还将利用所提供的职业发展计划 由UAB临床和翻译科学中心提供。该提案还旨在向PI提供正式的 比较有效性和保健服务方法方面的辅导培训以及研究培训 这将为他自己的调查生涯开辟新的途径，并为受训人员提供更多机会。 K24将对PI的长期职业目标做出重大贡献，以1)扩大我们对 COPD患者的心肺相互作用；2)进行高影响力的POR以改变对患有 3)帮助培训规划COPD POR职业生涯的下一代研究人员。

ABSTRACT COPD is the third leading cause of death in the United States and has major public health impacts. Current treatments can improve symptoms but none prevent disease progression or reduce mortality. This is in part due to the high burden of comorbidities, including cardiovascular disease, which complicate diagnosis and treatment. COPD-associated cardiovascular disease has not been adequately studied but may provide avenues to improve clinical outcomes. There are currently no proven therapies for COPD-related pulmonary vascular disease despite numerous trials testing vasodilators in patients with severe pulmonary hypertension. Conduct of these studies has been hampered by the lack of a non-invasive measure of pulmonary pressure and no tools adequately detect early pulmonary vascular abnormalities. We have developed a novel, non- invasive, cardiac MRI measure of pulmonary artery impedance (the velocity transfer function) that may prove useful in the identification and quantification of COPD-associated pulmonary vascular disease. Specific Aim 1 of this proposal is to determine whether the velocity transfer function can identify abnormalities in pulmonary arterial impedance in COPD and whether it correlates with right ventricular function. It is also well established that beta-blockers reduce mortality in patients with cardiovascular disease, but COPD patients are often denied these medications because of concerns about adverse effects of beta-blockade on airway function. Multiple observational studies now indicate that beta-blockers may in fact reduce exacerbation risk in COPD and the multicenter, randomized, placebo-controlled, Beta-Blocker for the Prevention of COPD Exacerbations (BLOCK- COPD) trial is underway to test this hypothesis. Regardless of the results, questions will remain about the risk- benefit of beta-blockers in patients with COPD, including their effects on exercise. Specific Aim 2 of this proposal is to determine the effect of metoprolol on peak exercise as assessed by cycle ergometry in patients with COPD. This proposal also aims to provide mentoring and training opportunities to new investigators pursuing COPD Patient-Oriented Research (POR). Mentoring will be tailored to meet the interests and objectives of individual trainees but a core set of topics will be presented through one-on-one and group sessions. Specialized training in biostatistics as well as research applications of quantitative thoracic CT and cardiac MRI will also be provided. Trainees will also take advantage of career development programs offered by the UAB Center for Clinical and Translational Science. The proposal also aims to provide the PI with formal mentoring training as well as research training in comparative effectiveness and health services methodology which will open new avenues for his own investigative career as well as additional opportunities for trainees. The K24 will contribute significantly to the PI's long term career objectives to 1) extend our understanding of cardiopulmonary interactions in COPD; 2) conduct high impact POR to transform care for patients with the disease; and 3) help train the next generation of investigators planning careers in COPD POR.