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

空气污染与健康和慢性阻塞性肺病中的肺部：阻塞性、限制性和血管通路

• 批准号: 9012513
• 负责人: Mary B Rice
• 金额: $ 17.67万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9012513
• 关键词: Acute; Address; Admission activity; Adult; Aerosols; Affect; Air; Air Pollutants; Air Pollution; American; Area; Autopsy; Award; Behavior Therapy; Biometry; Biopsy; Blood Vessels; Boston; Caliber; Cardiac; Chest; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Cicatrix; Clinical; Clinical Research; Clinical Sciences; Critical Care; Data; Development; Development Plans; Disease; Environment; Environmental Epidemiology; Environmental Exposure; Epidemic; Epidemiologist; Epidemiology; Exposure to; Fellowship; Forced expiratory volume function; Fossil Fuels; Framingham Heart Study; Future; General Population; Goals; Health; Home environment; Hospitals; Image; Image Analysis; Israel; Journals; Lung; Lung diseases; Measurable; Measurement; Measures; Medical center; Medicine; Mentors; Mentorship; Modeling; Monitor; Morphology; Nitrogen Dioxide; Obstructive Lung Diseases; Optics; Ozone; Participant; Particulate Matter; Pathway interactions; Patients; Pattern; Peak Expiratory Flow Rate; Peripheral; Physicians; Play; Pollution; Population; Predisposition; Prospective Studies; Public Health Education; Public Health Schools; Publications; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Mass; Pulmonary vessels; Questionnaires; Recruitment Activity; Research; Research Personnel; Resources; Respiratory Signs and Symptoms; Respiratory physiology; Rice; Risk; Risk Factors; Role; Sampling; Scanning; Severities; Site; Smoker; Smoking; Spirometry; Staging; Structural defect; Structure; Symptoms; Testing; Thick; Tobacco smoke; Total Lung Capacity; Training; Translating; Translational Research; United States Environmental Protection Agency; Vascular Diseases; Vascular remodeling; Ventricular; Vital capacity; Woman; Work; X-Ray Computed Tomography; alveolar destruction; ambient air pollution; attenuation; base; career; career development; catalyst; cohort; constriction; exercise capacity; experience; extrastriate visual cortex; interstitial; light weight; lung volume; medical schools; mortality; multidisciplinary; novel; particle; pollutant; population based; prevent; professor; public health relevance; quantitative imaging; respiratory; skills; tool; trafficking

 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.

 描述（由申请人提供）：玛丽赖斯博士是一名肺病学家，其长期职业目标是成为一名独立的翻译研究者，专注于了解环境暴露如何影响慢性肺病的发展和进展。她的研究工作集中在心脏病研究中短期和长期暴露于环境空气污染和肺功能的研究。在这项基于人群的成人研究中，她发现，在当前标准范围内，前一天的空气污染暴露与肺功能降低有关，长期污染暴露与肺功能加速下降有关。她的研究成果在全国肺病研究员研究竞赛中获得第一名，并在《美国呼吸和重症监护医学杂志》上发表了两篇第一作者论文。赖斯博士提出了新的研究，将推动该领域的发展，并建立在这些发现和她在公共卫生硕士培训期间获得的技能的基础上，了解这些浓度的污染如何影响慢性肺部疾病的发展和进展。她的近期职业目标是（1）获得环境流行病学，生物统计学和定量胸部CT分析在研究中的应用方面的正式和应用培训，以及（2）获得实际的 建立慢性阻塞性肺病（COPD）队列并评估该人群的污染暴露、呼吸道症状和肺功能的技能。工作环境：在她的共同导师Murray Mittleman博士和乔治沃什科博士的指导下，赖斯博士制定了一个全面的职业发展计划，以实现这些目标。Beth Israel Deaconess Medical Center（BIDMC）和哈佛公共卫生学院（HSPH）的哈佛流行病学教授Mittleman MD DrPH博士将担任Rice博士的主要导师，因为他在她的研究奖学金期间已经将近3年了。Mittleman博士是一位著名的流行病学医生，擅长研究污染暴露的急性和慢性影响。他在指导学员独立方面有着悠久的历史，并因其导师角色而获奖。沃什科博士，拟议的共同导师，是一个肺病学家和主任胸部成像实验室在布里格姆妇女医院，副主任心脏研究肺研究中心。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。Rice博士将在BIDMC的肺部和重症监护部门工作，该部门致力于将她提升为转化研究的未来领导者，重点是了解慢性肺部疾病的环境起源，特别是COPD。赖斯博士将获得哈佛催化剂临床和转化科学奖的支持，该奖项将为她关于污染暴露对COPD患者呼吸影响的新研究在BIDMC临床研究中心提供研究空间和资源。本研究将为未来的R 01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、呼吸流行病学和环境生物统计学方面具有世界一流专业知识的多学科咨询委员会。调研：在她的前两个目标中，Rice博士提出了对长期暴露于交通和细颗粒物的分析，通过使用基于卫星的大气柱中颗粒丰度估计的复杂模型进行估计，以及（1）测量肺气肿，气道厚度，肺容量和间质性肺异常，以及（2）在心脏研究中测量胸部CT上的肺血管形态。这项工作建立在她以前在这个队列中的工作，以确定长期污染暴露是否会导致阻塞性肺病（肺泡破坏和气道增厚），限制性肺病（肺实质瘢痕使肺变硬和收缩）和/或肺血管疾病（外周血管收缩或修剪）。先前的肺功能研究表明，长期暴露于空气污染可能会导致阻塞性和限制性影响，有限的证据表明，污染可能会增加右心室后负荷和质量，这可能是肺血管变化的结果。Rice博士假设，多年暴露于交通相关污染（如烟草烟雾）会导致肺气肿、气道增厚、间质异常和小口径外周肺血管体积减少。在她的第三个目标中，Rice博士提出了一项新的COPD患者前瞻性研究（n=30），以测试每天暴露于环境空气污染物之间的相关性，这些污染物是由波士顿中心站点和一种新型的轻型个人监测仪测量的，以及使用最先进的肺功能测定工具在家中每天测量呼吸症状和肺功能。尽管使用管理数据的研究发现，室外污染水平的日常增加与COPD入院和呼吸道死亡的风险增加有关，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，即使是轻微的肺功能变化也可能具有临床意义。这项研究将进一步了解暴露于相对较低水平的污染如何影响普通人群的肺结构，以及COPD患者的肺功能和症状。调查结果可以为空气质量标准提供信息，以保护公众和易感人群。COPD患者的个人污染暴露数据可能最终转化为行为干预，以预防COPD加重。