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

摘要/摘要 意义：慢性阻塞性肺疾病(COPD)是导致全球死亡的主要原因， 面临着特别大的风险。吸烟的女性患COPD的风险更高，疾病进展更快，死亡率也更高 与吸烟男性相比，即使在相似的烟草暴露水平下也是如此。在那些从未有过 吸烟后，慢性阻塞性肺疾病在女性中更为普遍。艾滋病毒是COPD风险的一个重要的非烟草相关的驱动因素， 全球一半以上的艾滋病毒携带者是妇女和女孩，但与艾滋病毒相关的COPD风险有何不同 在女性中的比例是未知的。推动女性COPD风险加重的机制是一个活跃的领域 研究发现，更年期过渡期间性激素的变化可能起到关键的机制作用。 携带艾滋病毒的妇女可能比未感染艾滋病毒的妇女有更早的生殖年龄，这可能会进一步 加剧了这一脆弱人群中的慢性阻塞性肺病风险。从历史上看，女性在 对COPD的研究和对HIV相关肺部疾病的研究，使人们更深入地了解 生殖老龄化对妇女肺部健康的影响对于确保妇女得到最全面的护理至关重要。 因感染艾滋病毒而变老。我们的首要目标是描述生殖衰老及其对肺部的相关影响。 乌干达艾滋病毒携带者和艾滋病毒感染妇女的健康状况。创新：明显优势包括：1)战略重点 在资源有限的情况下，大多数全球COPD死亡率发生在那里，大多数妇女生活在 HIV居住，因此我们的研究队列代表了环境、职业和传染性 受慢性阻塞性肺病和艾滋病毒流行影响的大多数妇女的暴露情况，2)利用井- 在全球环境中表征队列，拥有7年的肺功能和存储的血液样本，使我们能够 进行高级统计分析以表征复杂关系，以及3)一种新的基于生物标记物的 定义生殖年龄的方法，前瞻性地识别接近更年期的妇女。 调查人员：Markella Zanni博士，一位内分泌学家，在非 艾滋病毒携带者中的传染性并存，加入我的导师团队，指导与以下方面相关的方面 生殖衰老。方法：我们将利用储存了7年的血液样本来表征生殖 在父母K23队列中126名感染和未感染HIV的女性中的年龄，并将这些数据与历史肺脏配对 测试以下具体目的的功能数据：1)使用先前收集的人口统计和健康历史 数据，我将确定晚期生殖老化的预测因素；以及2)使用历史肺功能数据，我将 确定晚期生殖衰老是否改变或调节HIV与肺之间的关系 功能衰退。影响：这些数据将为我的K23资助工作提供更深入的 妇女中艾滋病毒和肺部健康的特征，将为未来的R01提案提供信息，旨在测试 干预措施，以减轻更年期相关的肺功能障碍，并将建立一个生殖健康的生物库 老龄化数据，可用于研究性别/性别对撒哈拉以南非洲其他健康结果的影响。

SUMMARY/ABSTRACT Significance: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality, and women are at particular risk. Women who smoke have higher COPD risk, faster disease progression, and rising mortality rates compared to men who smoke, even at similar levels of tobacco exposure. Among those who have never smoked, COPD is more prevalent among women. HIV is an important non-tobacco related driver of COPD risk, and over half the global population with HIV are women and girls, but how HIV-associated COPD risk differs among women is unknown. Mechanisms driving the accentuated COPD risk among women are an area of active investigation, but changes in sex hormones during the menopausal transition may play a key mechanistic role. Women with HIV may have more advanced reproductive aging than women without HIV, which may further compound the COPD risk in this vulnerable population. Women have historically been underrepresented in COPD studies and studies of HIV-associated lung disease, so a deeper understanding of the influence of reproductive aging on lung health among women is essential to ensure the most comprehensive care of women aging with HIV. Our overarching objective is to characterize reproductive aging and its associated effects on lung health among HIV+ and HIV- women in Uganda. Innovation: Distinct advantages include: 1) A strategic focus on women in a resource-limited setting, where most global COPD mortality occurs and most women living with HIV reside, and thus our study cohort is representative of the environmental, occupational, and infectious exposures for most women affected by the confluence of the COPD and HIV epidemics, 2) Leveraging a well- characterized cohort in a global setting with 7 years of lung function and stored blood samples, allowing us to conduct advanced statistical analyses characterizing complex relationships, and 3) A novel biomarker-based approach to defining reproductive aging that prospectively identifies women approaching menopause. Investigators: Dr. Markella Zanni, an endocrinologist with expertise in hormonal mechanisms of non- communicable comorbidities among people with HIV, joins my mentorship team to guide aspects related to reproductive aging. Approach: We will leverage 7 years of stored blood samples to characterize reproductive aging among 126 women with and without HIV in the parent K23 cohort and pair these data with historic lung function data to test the following Specific Aims: 1) Using previously-collected demographic and health history data, I will identify predictors of advanced reproductive aging; and 2) Using historic lung function data, I will determine whether advanced reproductive aging modifies or mediates the relationship between HIV and lung function decline. Impact: These data will complement my K23-funded work by providing a deeper characterization of HIV and lung health among women, will inform future R01 proposals designed to test interventions to mitigate menopause-related lung dysfunction, and will establish a biorepository of reproductive aging data that can be used to study the influence of sex/gender on other health outcomes in sub-Saharan Africa.