Air Pollution and the Lung in Health and COPD: Obstructive, Restrictive and Vascular Pathways

 简介(申请人提供)：玛丽·赖斯博士是一名肺科医生，她的长期职业目标是成为一名独立的翻译调查员，专注于了解环境暴露如何影响慢性肺部疾病的发展和进展。在弗雷明翰心脏研究中，她的研究重点是短期和长期暴露于环境空气污染和肺功能的研究。在这项以人群为基础的成人研究中，她发现，前一天暴露在当前标准内的空气污染与肺功能下降有关，长期污染暴露与肺功能加速下降有关。她的研究在全国肺部研究员研究竞赛中获得一等奖，并在《美国呼吸与重症护理医学杂志》上发表了两篇第一作者论文。赖斯博士提出的新研究将推动这一领域的发展，并以这些发现和她在公共卫生硕士培训期间获得的技能为基础，了解这些浓度的污染可能如何影响慢性肺部疾病的发展和进展。她目前的职业目标是(1)获得环境流行病学、生物统计学以及在研究中使用定量胸部CT分析的正式和应用培训；(2)获得实用的 具备建立慢性阻塞性肺疾病(COPD)队列、评估污染暴露、呼吸道症状和肺功能的技能。环境：在共同导师默里·米特尔曼博士和乔治·沃什科博士的指导下，赖斯博士制定了一项全面的职业发展计划，以实现这些目标。贝丝以色列女执事医疗中心(BIDMC)和哈佛大学公共卫生学院(HSPH)的哈佛大学流行病学教授Mittleman MD DrPH博士将担任赖斯博士的主要导师，就像他在她担任研究员期间近3年来所做的那样。米特尔曼博士是一位著名的内科流行病学家，在污染暴露的急性和慢性影响研究方面拥有专业知识。他在指导学员走向独立方面有着长期的记录，并因其导师角色而获奖。沃什科博士是一名肺科医生，是布里格姆妇女医院胸部成像实验室的主任，也是弗雷明翰心脏研究肺研究中心的副主任。他是在慢性阻塞性肺疾病(COPD)研究中使用定量成像分析的先驱。赖斯博士将在BIDMC的肺和重症护理部门工作，该部门致力于将她提升为未来转译研究的领导者，专注于了解慢性肺部疾病，特别是慢性阻塞性肺病的环境起源。赖斯博士将得到哈佛大学临床和转化科学奖的支持，该奖项将为她在BIDMC临床研究中心进行的关于污染暴露对COPD患者的呼吸影响的新研究提供研究空间和资源。这项研究将为未来的R01提案提供数据。此外，拟议的职业发展计划将利用HSPH和哈佛医学院的高级课程和研讨会，以及在空气污染暴露评估、呼吸道流行病学和环境生物统计学方面拥有世界级专业知识的多学科咨询委员会。研究：在她的前两个目标中，赖斯博士提出了对长期暴露在交通和细颗粒物中的分析，通过一个复杂的模型，使用基于卫星的大气柱中粒子丰度的估计来估计，以及(1)在弗雷明翰心脏研究中测量肺气肿、呼吸道厚度、肺体积和间质肺异常，以及(2)在胸部CT上测量肺血管形态。这项工作建立在她之前在这个队列中的工作基础上，以确定长期污染暴露是否会导致阻塞性肺疾病(伴有肺泡破坏和呼吸道增厚)、限制性肺部疾病(伴有使肺僵硬和收缩的实质疤痕)和/或肺血管疾病(伴有外周血管收缩或修剪)。先前对肺功能的研究表明，长期接触空气污染可能会导致梗阻和限制性影响，而有限的证据表明，污染可能会增加右室后负荷和质量，这可能是肺血管变化的结果。赖斯博士假设，多年暴露在与交通相关的污染中，如烟草烟雾，会导致肺气肿、呼吸道增厚、间质异常，以及小口径外周肺血管数量减少。在她的第三个目标中，赖斯博士提出了一项针对COPD患者(n=30)的新的前瞻性研究，以使用最先进的肺活量测量工具，测试波士顿中央监测站和一种新型轻型个人监测仪测量的每日环境空气污染物暴露与家庭呼吸症状和肺功能的日常测量之间的关联。尽管使用行政数据的研究发现，户外污染水平的逐日上升与COPD入院风险和呼吸系统死亡率的增加有关，但人们对当今水平的空气污染如何影响COPD患者的肺功能和症状知之甚少，对他们来说，即使是肺功能的轻微变化也可能具有临床意义。这项研究将促进对暴露在相对较低水平的污染中如何影响普通人群的肺结构以及COPD患者的肺功能和症状的理解。研究结果可能会为空气质量标准提供参考，以保护公众和易感人群。有关慢性阻塞性肺病患者个人污染暴露的数据最终可能转化为预防COPD病情恶化的行为干预措施。

 DESCRIPTION (provided by applicant): Dr. Mary Rice is a pulmonologist whose long-term career goal is to become an independent translational investigator focused on understanding how environmental exposures affect the development and progression of chronic lung disease. Her research efforts have focused on the study of short- and long-term exposure to ambient air pollution and lung function in the Framingham Heart Study. In this population-based study of adults, she has found that previous-day air pollution exposure within current standards is associated with lower lung function, and long-term pollution exposure is associated with accelerated lung function decline. Her research has resulted in a first place award in a national pulmonary fellows' research competition and two first author publications in the American Journal of Respiratory and Critical Care Medicine. Dr. Rice proposes new research that will move the field forward, and build on these findings and the skills she acquired during her Master's in Public Health training, to understand how pollution at these concentrations may affect the development and progression of chronic lung disease. Her immediate career objectives are (1) to obtain formal and applied training in environmental epidemiology, biostatistics, and the use of quantitative chest CT analysis in research, and (2) to gain practical skills in building a cohort with chronic obstructive pulmonary disease (COPD), and assessing pollution exposure, respiratory symptoms and lung function in this population. Environment: With the guidance of her co-mentors, Drs. Murray Mittleman and George Washko, Dr. Rice has formulated a comprehensive career development plan to accomplish these goals. Dr. Mittleman MD DrPH, Harvard Professor of Epidemiology at Beth Israel Deaconess Medical Center (BIDMC) and the Harvard School of Public Health (HSPH), will serve as Dr. Rice's primary mentor, as he has for nearly 3 years during her research fellowship. Dr. Mittleman is a renowned physician epidemiologist with expertise in the study of acute and chronic effects of pollution exposure. He has a long track record of mentoring trainees to independence and has won awards for his mentorship role. Dr. Washko, the proposed co-mentor, is a pulmonologist and Director of the Chest Imaging Lab at Brigham and Women's Hospital, and Associate Director of the Framingham Heart Study Pulmonary Research Center. He is a pioneer in the use of quantitative imaging analysis in the study of chronic obstructive pulmonary disease (COPD). Dr. Rice will be based within the Division of Pulmonary and Critical Care at BIDMC, which is deeply committed to promoting her as a future leader in translational research focused on understanding the environmental origins of chronic lung disease, and COPD in particular. Dr. Rice will be supported by the Harvard Catalyst Clinical and Translational Science Award, which will provide research space and resources at the BIDMC Clinical Research Center for her new study of the respiratory effects of pollution exposure in people with COPD. This study will provide data for a future R01 proposal. Additionally, the proposed career development plan will take advantage of advanced classes and seminars at HSPH and Harvard Medical School, and a multidisciplinary advisory board with world-class expertise in air pollution exposure assessment, respiratory epidemiology and environmental biostatistics. Research: In her first two aims, Dr. Rice proposes analyses of long-term exposure to traffic and fine particulate matter, estimated by a sophisticated model using satellite-based estimates of particle abundance in the atmospheric column, and (1) measures of emphysema, airway thickness, lung volumes and interstitial lung abnormalities, and (2) measures of pulmonary vascular morphology on chest CT in the Framingham Heart Study. This work builds on her prior work in this cohort to determine if long-term pollution exposure contributes to obstructive lung disease (with alveolar destruction and airway thickening), restrictive lung disease (with parenchymal scarring that stiffens and shrinks the lung), and/or pulmonary vascular disease (with constriction or pruning of the peripheral vasculature). Prior studies of lung function indicate that long-term air pollution exposure may cause obstructive and restrictive effects, and limited evidence suggests pollution may increase right ventricular afterload and mass, possibly a result of pulmonary vascular change. Dr. Rice hypothesizes that years of exposure to traffic-related pollution, like tobacco smoke, contributes to emphysema, airway thickening, interstitial abnormalities, and a lower volume of small caliber peripheral pulmonary vessels. In her third aim, Dr. Rice proposes a new prospective study of people with COPD (n=30) to test associations between daily exposure to ambient air pollutants measured by central site in Boston and also by a novel, light-weight personal monitor, and daily measurements of respiratory symptoms and lung function at home, using state-of-the art spirometry tools. Although studies using administrative data have found that day-to-day increases in outdoor pollution levels are associated with increased risk of COPD admissions and respiratory mortality, little is known about how air pollution at today's levels affects lung function and symptoms in people with COPD, for whom even modest changes in lung function may have clinical importance. This research will advance understanding of how exposure to pollution at relatively low levels affects lung structure in the general population, and lung function and symptoms in people with COPD. Findings may inform air quality standards to protect the public and susceptible populations. Data on personal pollution exposure in COPD may ultimately translate to behavioral interventions to prevent COPD exacerbations.