UAB Mentoring Program in COPD Patient Oriented Research

摘要 COPD是美国第三大死亡原因，对公共卫生有重大影响。电流 治疗可以改善症状，但不能阻止疾病进展或降低死亡率。这部分是 由于包括心血管疾病在内的合并症负担高，使诊断复杂化， 治疗COPD相关的心血管疾病尚未得到充分研究，但可能提供 改善临床结果的途径。目前尚无经证实的治疗COPD相关肺部疾病的方法。 尽管有许多试验在严重肺动脉高压患者中测试血管扩张剂，但仍存在血管疾病。 由于缺乏无创的肺压测量方法，这些研究的开展受到了阻碍 并且没有工具能够充分检测早期肺血管异常。我们开发了一个新的，非- 肺动脉阻抗（速度传递函数）的侵入性心脏MRI测量可以证明 可用于COPD相关肺血管疾病的鉴定和定量。具体目标1 该建议的目的是确定速度传递函数是否可以识别肺动脉中的异常， COPD患者的动脉阻抗及其是否与右心室功能相关。它也是公认的 β受体阻滞剂降低心血管疾病患者的死亡率，但COPD患者往往被否认 因为担心β受体阻滞剂对气道功能的副作用，多 现在的观察性研究表明，β受体阻滞剂实际上可能降低COPD急性加重的风险， 多中心、随机、安慰剂对照、β受体阻滞剂预防COPD急性加重（BLOCK- COPD）试验正在进行中，以验证这一假设。不管结果如何，关于风险的问题仍然存在- β受体阻滞剂对COPD患者的益处，包括其对运动的影响。具体目标2 建议通过踏车测力计评估患者的美托洛尔对峰值运动的影响 COPD。这项提议还旨在为新调查员提供辅导和培训机会 COPD患者导向研究（POR）指导将根据学生的兴趣和 个人的目标，但一套核心的主题将通过一对一和小组提出 sessions.生物统计学专业培训以及定量胸部CT的研究应用， 还将提供心脏MRI。学员还将利用提供的职业发展计划 UAB临床和转化科学中心该提案还旨在为PI提供正式的 在比较效果和保健服务方法方面的指导培训以及研究培训 这将为他自己的调查事业开辟新的途径，并为受训人员提供更多的机会。 K24将为PI的长期职业目标做出重大贡献，以1）扩展我们对以下方面的理解： COPD中的心肺相互作用; 2）进行高影响POR，以改变对COPD患者的护理， 疾病;和3）帮助培训下一代研究人员规划COPD POR的职业生涯。

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.