The influence of air pollution on lung health among people living with HIV.

项目总结/摘要 背景：四分之一的COPD患者-全球9600万人-从未吸烟。最 COPD死亡率发生在世界上吸烟不常见的地区，如撒哈拉以南非洲，那里的艾滋病毒 空气污染可能导致约2600万非洲COPD患者死亡。人 艾滋病毒感染者（PLWH）经历持续的全身炎症和慢性肺部疾病的风险增加。 像艾滋病毒一样，空气污染-全球死亡的主要环境原因-会导致全身炎症， 对肺部健康有很大影响。艾滋病毒和空气污染通过类似的炎症途径起作用， 对肺组织有破坏性。因此，暴露于空气污染的艾滋病毒携带者可能面临特别高的肺部感染风险。 疾病如果共同的炎症途径加重了暴露于空气污染的PLWH的肺部疾病风险， 那么针对这些途径可能会产生巨大的临床影响。这个项目的假设是， 与未感染艾滋病毒的人相比，他们经历了更严重的空气污染相关的肺部炎症和肺功能障碍。 我帮助建立了一个为期四年的合作，马萨诸塞州总医院，姆巴拉拉大学， 科学与技术，以及哈佛T. H. Chan公共卫生学院已启用空气质量监测 在乌干达西南部，并准备调查这一新的研究领域。饰演角色：Dr. North 总体职业目标是成为一名独立的调查员，专注于环境暴露和肺 艾滋病毒/艾滋病感染者的健康。她的临床工作照顾慢性肺病患者和领导研究 调查乌干达慢性肺病的流行病学激发了她的职业道路。她很好- 准备承担这里提出的科学和培训目标，成功地出版了八个第一- 作者手稿，三个中间作者手稿，并完成了2016年农村空气质量的试点研究 乌干达导师：Mark Siedner博士（主要导师）是NIH资助的研究者，他成功地 4名NIH K获奖者。彼得罗斯Koutrakis博士（个人空气污染测量），Bethany Hedt-Gauthier （生物统计学）和Benjamin Medoff（免疫介导的肺损伤）将提供额外的重点指导 确保诺斯博士的成功研究：利用R 01资助的300名艾滋病毒感染者和300名 年龄和性别相似，未感染艾滋病毒的参与者，诺斯博士将增加个人空气污染监测， 研究性支气管镜检查与正在进行的研究程序相结合，以表征个人空气污染暴露， 研究空气污染、肺部炎症和肺功能之间的关系。训练：为了实现她的目标 要想成为一名独立的研究人员，诺斯博士需要在个人空气污染方面接受额外的培训 测量，2）先进的生物统计学，包括结构方程模型，和3）免疫介导的肺 损伤基于她以前的研究经验，不断扩大的出版记录，出色的指导团队， 强有力的机构承诺，和创新的研究计划，诺斯博士是有能力成为一个 独立的临床研究者专注于环境暴露和肺健康之间的PLWH。

PROJECT SUMMARY/ABSTRACT Background: One in four people living with COPD – 96 million people worldwide – have never smoked. Most COPD mortality occurs in regions of the world where smoking is uncommon, like sub-Saharan Africa, where HIV and air pollution may be driving COPD mortality among the estimated 26 million Africans with COPD. People living with HIV (PLWH) experience persistent systemic inflammation and increased risk of chronic lung disease. Like HIV, air pollution – the leading environmental cause of death globally – causes systemic inflammation and significantly worsens lung health. HIV and air pollution operate through similar inflammatory pathways that are destructive to lung tissues. Thus, PLWH who are exposed to air pollution may face particularly high risk of lung disease. If shared inflammatory pathways accentuate lung disease risk among PLWH exposed to air pollution, then targeting these pathways could have outsized clinical impact. The hypothesis of this project is that PLWH experience greater air pollution-associated lung inflammation and lung dysfunction than HIV-uninfected people. I helped establish a four-year collaboration between Massachusetts General Hospital, Mbarara University of Science and Technology, and Harvard T.H. Chan School of Public Health that has enabled air quality monitoring in southwestern Uganda and is poised to investigate this novel area of research. Candidate: Dr. North's overarching career goal is to become an independent investigator focused on environmental exposures and lung health among PLWH. Her clinical work caring for patients with chronic lung disease and leading research investigating the epidemiology of chronic lung disease in Uganda have inspired this career path. She is well- prepared to undertake the scientific and training aims proposed here, having successfully published eight first- author manuscripts, three middle-author manuscripts, and completed a 2016 pilot study of air quality in rural Uganda. Mentoring: Dr. Mark Siedner (Primary mentor) is an NIH-funded investigator who has successfully mentored 4 NIH K awardees. Drs. Petros Koutrakis (personal air pollution measurement), Bethany Hedt-Gauthier (biostatistics), and Benjamin Medoff (immune-mediated lung injury), will provide additional focused mentoring to ensure Dr. North's success. Research: Leveraging an ongoing, R01-funded cohort of 300 HIV-infected and 300 age- and sex-similar, HIV-uninfected participants, Dr. North will add personal air pollution monitoring and research bronchoscopy to ongoing study procedures in order to characterize personal air pollution exposure and examine relationships between air pollution, lung inflammation and lung function. Training: To achieve her aims and become an independent researcher, Dr. North requires additional training in 1) personal air pollution measurement, 2) advanced biostatistics including structural equation modeling, and 3) immune-mediated lung injury. Based on her previous research experience, expanding publication record, exceptional mentoring team, strong institutional commitment, and innovative research plan, Dr. North is well-positioned to become an independent clinical investigator focused on environmental exposures and lung health among PLWH.