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

项目摘要/摘要 背景：每四名COPD患者中就有一人--全球9600万人--从未吸烟。多数 COPD死亡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 空气污染可能是导致约2600万非洲慢性阻塞性肺病患者死亡的原因。人民 艾滋病毒携带者(PLWH)经历持续的全身炎症和慢性肺部疾病风险增加。 与艾滋病毒一样，空气污染--全球主要的环境死亡原因--会导致全身炎症和 会严重恶化肺部健康。艾滋病毒和空气污染通过类似的炎症途径运作，这些途径 对肺组织具有破坏性。因此，暴露于空气污染中的PLWH可能会面临特别高的肺部风险。 疾病。如果共同的炎症途径加剧了暴露在空气污染中的PLWH的肺部疾病风险， 那么以这些通路为靶点可能会产生超乎寻常的临床影响。这个项目的假设是PLWH 与未感染艾滋病毒的人相比，经历更严重的空气污染相关的肺部炎症和肺功能障碍。 我帮助马萨诸塞州总医院、姆巴拉拉大学 和哈佛大学公共卫生学院合作，使空气质量监测成为可能 在乌干达西南部，并准备研究这一新的研究领域。候选人：诺斯医生的 首要的职业目标是成为一名专注于环境暴露和肺部的独立调查员 公共卫生部门的健康状况。她的临床工作照顾慢性肺病患者并领导研究 在乌干达调查慢性肺病的流行病学启发了这条职业道路。她很好- 准备承担这里提出的科学和培训目标，成功地发布了八个首批- 作者稿件，三篇中等作者稿件，并完成了2016年农村空气质量试点研究 乌干达。指导：Mark Siedner博士(首席导师)是NIH资助的一名研究人员，他成功地 指导了4名NIH K奖获得者。Petros Koutrakis博士(个人空气污染测量)，Bathany Hedt-Gauthier (生物统计学)和Benjamin Medoff(免疫介导的肺损伤)，将提供额外的有重点的指导 确保诺斯博士的成功。研究：利用R01资助的持续队列，包括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和 研究支气管镜检查以进行正在进行的研究程序，以表征个人空气污染暴露和 检查空气污染、肺部炎症和肺功能之间的关系。培训：实现她的目标 要成为一名独立研究人员，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)高级生物统计学，包括结构方程建模，以及3)免疫介导的肺 受伤。根据她以前的研究经验，不断扩大的出版记录，出色的指导团队， 坚定的机构承诺和创新的研究计划，诺斯博士处于有利地位，将成为 独立的临床调查员专注于PLWH中的环境暴露和肺健康。

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.