Air Pollution's Impact on Lung Aging in HIV

空气污染对艾滋病毒肺部衰老的影响

• 批准号: 10478375
• 负责人: Sarath Raju
• 金额: $ 19.79万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10478375
• 关键词: Address; Affect; Age; Aging; Air; Air Pollution; Award; Baltimore; Biological; Biological Aging; Biological Markers; Chronic; Chronic Disease; Clinical; Cohort Studies; DNA Methylation; Data; Development; Development Plans; Dimensions; Disease; Disease Marker; Environment; Environmental Exposure; Epigenetic Process; Etiology; Exposure to; Face; Functional disorder; Funding; General Population; Goals; HIV; HIV Infections; Health; Household Air Pollution; Image; Individual; Inflammation; Infrastructure; Knowledge; Lead; Life Expectancy; Lung; Lung diseases; Measurement; Measures; Mediating; Mentors; Mentorship; Methods; Modeling; Nitrogen Dioxide; Ozone; Parents; Participant; Particulate Matter; Pathway interactions; Persons; Phenotype; Physicians; Physiological; Pollution; Population; Populations at Risk; Positioning Attribute; Predisposition; Prospective cohort; Pulmonary Emphysema; Quality of life; Research; Resolution; Resources; Respiratory Disease; Risk; Risk Factors; Role; Scientist; Techniques; Testing; Thoracic Radiography; Training; Vulnerable Populations; X-Ray Computed Tomography; age effect; age related; ambient air pollution; career; career development; chest computed tomography; chronic respiratory disease; cigarette smoke; clinical care; cohort; comorbidity; environmental health disparity; epigenetic marker; experience; fine particles; health related quality of life; high risk population; improved; lung health; modifiable risk; molecular marker; novel; pollutant; prospective; pulmonary function; pulmonary function decline; radiological imaging; respiratory; respiratory health; respiratory morbidity; response; small airways disease; tool; training opportunity; translational study

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.

项目摘要 如今，患有艾滋病毒（PLWH）的人面临着慢性呼吸道疾病和 加速肺老化。尽管研究进展增加了我们对肺部疾病的理解 在PLWH中，我们对影响肺部健康的因素有很大的差距 人口。全球环境空气污染仍然是一个重大但可改变的，造成了慢性的贡献者 呼吸发病和疾病的发展。虽然翻译研究表明艾滋病毒增加 对香烟烟雾的敏感性，这是否适用于长期环境空气污染暴露尚未 Studiod。迄今为止，长期空气污染对艾滋病毒肺老化的影响仍然未知。这 研究肺病病因（SHIELD）的HIV感染研究，这是一个前瞻性队列，由2600名患者组成 或在马里兰州巴尔的摩的艾滋病毒危险中，提供了一个理想的平台，可以有效回答有关影响的问题 PLWH肺衰老的环境。在现有盾牌队列的基础上，我们旨在确定是否是否 长期环境空气污染是高危人群中加速肺部衰老的驱动力，如果 PLWH更容易受到污染物暴露的呼吸健康影响。 拟议的研究将独特地表征环境，艾滋病毒和肺部衰老之间的相互作用。 我们将通过增强的精度，深入的CT添加定义的长期环境空气污染的度量 捕获早期肺部疾病的表型，以及生物衰老的分子标记和对 曝光，同时利用明确定义的PLWH队列的纵向肺功能数据。我们建议 三个旨在研究长期暴露对多维（生理，射线照相和射线照相和 PLWH中的生物学）肺老化。 （目标1）确定长期环境污染物之间的关联 暴露和生理肺老化（肺功能下降的轨迹）和与健康相关的生活质量 PLWH和可比的HIV未感染参与者； （目标2）定义长期污染物暴露的影响 PLWH中的射线照相肺老化（小气道疾病，空气诱捕，肺气肿）的CT测量； （目标3）确定长期污染物暴露与加速“生物学”衰老之间的关联， 通过表观遗传时钟测量，这是生物反应的分子标记和对污染物的敏感性 接触。在所有目标中，我们将研究艾滋病毒控制的艾滋病毒和标志物如何增加对空气污染的敏感性。 该提案将在实施环境队列研究的实施中提供培训 HIV肺疾病研究，晚期生物抑制方法，新型CT分析技术的复杂性 表型，以及表观遗传标志物在描述生物学反应和易感性的应用 暴露。职业发展计划包括专家精力，正式课程和动手 促进Raju博士实现自己的职业目标的经验 环境健康差异，艾滋病毒和肺部健康研究的交汇处的专业知识。