Air Pollution's Impact on Lung Aging in HIV

项目总结 今天，艾滋病毒携带者面临着不成比例的慢性呼吸道疾病和 加速了肺部衰老。尽管研究的进步增加了我们对肺部疾病的了解 在PLWH中，我们对这一高危人群中影响肺健康的因素的认识存在显著差距。 人口。全球环境空气污染仍然是慢性空气污染的一个重要但可改变的因素 呼吸道发病率和疾病发展。虽然翻译研究表明艾滋病毒增加了 对香烟烟雾的易感性，这是否适用于长期接触环境空气污染一直没有得到 学习。到目前为止，长期接触空气污染对艾滋病毒患者肺老化的影响仍不清楚。这个 HIV感染在肺部疾病病因学中的研究(SHIELD)，对2600名患有 马里兰州巴尔的摩的艾滋病毒高危人群提供了一个理想的平台，可以有效地回答有关 环境对PLWH肺老化的影响。在现有盾牌队列的基础上，我们的目标是确定 在高危人群中，长期的环境空气污染是加速肺老化的一个驱动因素，如果 PLWH更容易受到污染物暴露对呼吸健康的影响。 这项拟议的研究将独特地描述环境、艾滋病毒和肺老化之间的相互作用。 增加长期环境空气污染精细化措施，提高精确度、深度CT 用于捕捉早期肺部疾病的表型，以及生物老化和易感性的分子标志物 暴露，同时利用来自明确定义的PLWH队列的纵向肺功能数据。我们建议 三个目标是研究长期暴露对多维(生理学、放射学和 生物学)PLWH的肺老化。(目标1)确定长期环境污染物之间的关联 暴露和生理性肺老化(肺功能下降的轨迹)与健康相关的生活质量 公共卫生部门和类似的未感染艾滋病毒的参与者；(目标2)确定长期接触污染物的影响 PLWH患者肺部老化的CT表现(小气道疾病、空气滞留、肺气肿)； (目标3)确定长期接触污染物与加速“生物”老化之间的联系， 通过表观遗传时钟进行测量，表观遗传时钟是生物反应和对污染物敏感性的分子标记 曝光。在所有目标中，我们将研究艾滋病毒和艾滋病毒控制标志物如何增加对空气污染的易感性。 这项提议将在实施环境队列研究方面提供指导培训，即 HIV-肺部疾病研究的复杂性、先进的生物统计方法、新的肺部CT分析技术 表型，以及表观遗传标记在描述生物反应和易感性方面的应用 曝光。职业发展计划包括专家指导、正式课程和实践。 帮助Raju博士实现他的职业目标--成为一名独立的内科科学家 在环境健康差距、艾滋病毒和肺部健康研究方面的专业知识。

PROJECT SUMMARY Today, persons living with HIV (PLWH) face a disproportionate burden of chronic respiratory disease and accelerated lung aging. Despite advances in research that have increased our understanding of lung disease among PLWH, there are significant gaps in our knowledge of factors that impact lung health in this at-risk population. Worldwide ambient air pollution remains a significant, but modifiable, contributor to chronic respiratory morbidity and disease development. While translational studies suggest that HIV increases susceptibility to cigarette smoke, whether this applies to long-term ambient air pollution exposure has not been studied. To date, the impact of long-term air pollution exposure on lung aging in HIV remains unknown. The Study of HIV Infection in the Etiology of Lung Disease (SHIELD), a prospective cohort of 2600 individuals with or at-risk for HIV in Baltimore, MD, provides an ideal platform to efficiently answer questions about the impact of the environment on lung aging for PLWH. Building on the existing SHIELD cohort, we aim to determine if long-term ambient air pollution is a driver of accelerated lung aging in a high-risk population, and if PLWH are more susceptible to the respiratory health effects of pollutant exposure. The proposed research will uniquely characterize the interaction between the environment, HIV, and lung aging. We will add refined measures of long-term ambient air pollution with enhanced precision, in-depth CT phenotyping to capture early lung disease, and molecular markers of biologic aging and susceptibility to exposures, while leveraging longitudinal lung function data from a well-defined cohort of PLWH. We propose three aims to study the impact of long-term exposures on multidimensional (physiologic, radiographic, and biologic) lung aging among PLWH. (Aim 1) To determine the association between long-term ambient pollutant exposure and physiologic lung aging (trajectory of lung function decline) and health related quality of life for PLWH and comparable HIV-uninfected participants; (Aim 2) To define the impact of long-term pollutant exposure on CT measures of radiographic lung aging (small airways disease, air trapping, emphysema) among PLWH; (Aim 3) To determine the association between long-term pollutant exposure and accelerated “biologic” aging, measured via the epigenetic clock, a molecular marker of biologic responses and susceptibility to pollutant exposure. In all aims we will examine how HIV and markers of HIV control increase susceptibility to air pollution. This proposal will provide mentored training in the implementation of an environmental cohort study, the complexities of HIV-lung disease research, advanced biostatical methods, novel CT analysis techniques for lung phenotyping, and the application of epigenetic markers to describe biologic responses and susceptibility to exposures. The career development plan includes expert mentorship, formal coursework, and hands-on experience to facilitate Dr. Raju in achieving his career goal of becoming an independent physician scientist with expertise at the intersection of environmental health disparities, HIV, and lung health research.