Inflammation, Aging, Microbes, Obstructive Lung Disease, and Diffusion Abnormalities (I AM OLD-DA): Pulmonary function in females, evaluating the menopausal transition and immune activation (pFEMI).

摘要 尽管感染艾滋病毒的妇女在发展和健康方面具有更高的风险， 与男性HIV感染者相比，HIV相关合并症的进展。代表一个主要的 是造成全球寿命损失年数和艾滋病毒感染者第二大常见并发症的因素， 阻塞性肺疾病（OLD）是PWH全球重要的健康优先事项。老承诺增加 随着艾滋病毒感染者年龄的增长以及吸烟和生物质燃料暴露等老年人风险因素的增加， 继续与肺结核等疾病发生冲突。感染艾滋病毒的妇女特别容易受到 老年人;不仅艾滋病毒血清阴性妇女表现出对老年人发展的易感性增加， 但感染艾滋病毒的女性的免疫激活标志物水平总体上有所增加，其中许多标志物已经被 与肺功能障碍有关然而，在老年痴呆症患者中是否存在性别差异， 被很好地描述了。明确PWH患者肺功能障碍的性别差异， 性别特异性机制在老年人的风险，我们提出了一个补充NHLBI资助的炎症，衰老， 微生物、阻塞性肺疾病和弥散抑制（I AM OLD-DA）研究。在当前的I AM OLD-DA研究，我们正在进行一系列肺功能测试，以测量肺功能和弥散量 一氧化碳（DLco）随着时间的推移，以及分析12个炎症生物标志物，在我们建立的 在弗朗西斯科、加州和乌干达坎帕拉的队列中， 疾病，并阐明其潜在机制。到目前为止，我们已经发现了一个独特的生物标志物签名， PWH中的肺功能障碍。此外，在我们的试点数据分析中，我们发现， 与感染艾滋病毒的男子相比，感染艾滋病毒的妇女的老年人比例更高，这一差异在男女之间并不存在 没有艾滋病毒，这表明一个潜在的艾滋病毒特异性的性别差异，对我们的研究有重要意义。 了解艾滋病毒感染者和非艾滋病毒感染者中的老年人。在这份补充文件中，我们将讨论是否有 在我们的乌干达队列中，通过添加性激素和 性别分层生物标志物。该项目将是第一个此类项目：（1）评估基于性别的差异， 在国际环境中PWH的肺功能测定和DLco（目标1）;（2）将肺功能测定和DLco与性别进行比较- 分层生物标志物（目标2）;（3）通过研究性别和生育年龄对老年性痴呆的作用， 测量性激素（目标3）。本补充提案涉及ORWH战略中的三个 目标（战略目标1、2和4），通过增加侧重于性别差异的样本。应该 某些生物标志物、生育年龄和艾滋病毒感染妇女的老年痴呆症之间存在关系，这可能 为女性肺功能障碍的性别差异的潜在机制提供关键见解 有和没有艾滋病毒，并可用于确定性别特异性筛选和治疗目标的妇女 国际吧

Abstract Women with HIV remain underrepresented in research despite possessing a higher risk for the development and progression of HIV-associated comorbidities compared to men with HIV. Representing one of the major contributors to global years of life lost and the second most common comorbidity in people with HIV (PWH), obstructive lung disease (OLD) is an important health priority for PWH worldwide. OLD promises to increase in importance as the HIV population ages and as OLD risk factors such as smoking and biomass fuel exposure continue to collide with medical conditions such as tuberculosis. Women with HIV are particularly vulnerable to OLD; not only have HIV seronegative women demonstrated increased susceptibility for the development of OLD, but women with HIV have overall increased levels of immune activation markers, many of which have been linked to pulmonary dysfunction. However, whether sex-based differences in OLD exist among PWH has not been well characterized. To define sex-based differences in pulmonary dysfunction in PWH and to investigate sex-specific mechanisms in OLD risk, we propose a supplement to the NHLBI funded Inflammation, Aging, Microbes, Obstructive Lung Disease, and Diffusion Abnormalities (I AM OLD-DA) study. Under the current I AM OLD-DA study, we are performing serial pulmonary function tests to measure spirometry and diffusing capacity for carbon monoxide (DLco) over time as well as analyzing 12 inflammatory biomarkers in our established cohorts in San Francisco, California and Kampala, Uganda to better characterize HIV-associated pulmonary disease and to elucidate its underlying mechanisms. Thus far, we have found a distinct biomarker signature for pulmonary dysfunction in PWH. Further, in our pilot data analysis, we found over a four-fold increase in odds of OLD in women with HIV as compared to men with HIV, a disparity that was not seen between women and men without HIV, indicating a potential HIV-specific sex-based difference that has important implications for our understanding of OLD in persons with and without HIV. With this supplement, we will address whether there are sex-specific drivers for pulmonary dysfunction in our Ugandan cohort through the addition of sex hormones and sex-stratified biomarkers. This project would be the first of its kind in: (1) evaluating sex-based differences in spirometry and DLco in PWH in an international setting (Aim 1); (2) comparing spirometry and DLco to sex- stratified biomarkers (Aim 2); and (3) examining the role of sex and reproductive age on OLD through the measurement of sex hormones (Aim 3). This supplement proposal addresses three of the ORWH Strategic Goals (Strategic Goals 1, 2, and 4) through the addition of samples that focus on sex-based differences. Should there be a relationship between certain biomarkers, reproductive age, and OLD in women with HIV, this could provide key insights into underlying mechanisms in sex-based differences in pulmonary dysfunction for women with and without HIV and could be used to identify sex-specific screening and therapeutic targets for women worldwide.