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).

炎症、衰老、微生物、阻塞性肺疾病和扩散异常 (I AM OLD-DA)：女性肺功能，评估绝经过渡和免疫激活 (pFEMI)。

• 批准号: 10556269
• 负责人: LAURENCE HUANG
• 金额: $ 15.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556269
• 关键词: Address; Age; Aging; Applications Grants; Automobile Driving; Biological Markers; Body mass index; California; Carbon Monoxide; Categories; Cessation of life; Data; Data Analyses; Development; Diffuse; Diffusion; Disease; Female; Frequencies; Functional disorder; Funding; Future; General Population; Goals; Gonadal Steroid Hormones; HIV; HIV Seronegativity; Health Priorities; Immune; Inflammation; Inflammatory; International; Link; Lung; Lung diseases; Measurement; Measures; Medical; Menopausal Status; Menopause; Microbe; National Heart, Lung, and Blood Institute; Obstructive Lung Diseases; Pathway interactions; Persons; Phenotype; Population; Positioning Attribute; Predisposition; Publishing; Pulmonary function tests; Reporting; Research; Risk; Risk Factors; Role; Sampling; San Francisco; Sex Differences; Smoking; Smoking History; Spirometry; Time; Tuberculosis; Uganda; Woman; advanced maternal age; age related; base; biomarker evaluation; biomarker signature; biomass fuel; cigarette smoking; cohort; comorbidity; comparative; disorder risk; experience; high risk; immune activation; insight; men; mullerian-inhibiting hormone; premature; pulmonary function; reproductive; screening; sex; specific biomarkers; therapeutic target; tobacco smoke exposure; years of life lost

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.

抽象的 尽管女性感染艾滋病毒的风险较高，但在研究中的代表性仍然不足。 与感染艾滋病毒的男性相比，艾滋病毒相关合并症的进展。代表主要之一 导致全球寿命损失的因素以及艾滋病毒感染者 (PWH) 中第二常见的合并症， 阻塞性肺病（OLD）是全世界感染者健康的一个重要优先事项。 OLD承诺增加 随着艾滋病毒人口老龄化以及吸烟和生物质燃料暴露等老年风险因素的重要性 继续与结核病等疾病发生冲突。感染艾滋病毒的妇女特别容易受到感染 老的;艾滋病毒血清阴性的女性不仅更容易患上老年痴呆症， 但感染艾滋病毒的女性的免疫激活标记物水平总体升高，其中许多已被 与肺功能障碍有关。然而，PWH 中 OLD 是否存在基于性别的差异尚不清楚。 得到了很好的表征。定义 PWH 肺功能障碍的性别差异并进行调查 OLD 风险中的性别特异性机制，我们建议对 NHLBI 资助的炎症、衰老、 微生物、阻塞性肺疾病和扩散异常 (I AM OLD-DA) 研究。在当前的 I AM 下 OLD-DA 研究，我们正在进行系列肺功能测试以测量肺量测定和弥散能力 随时间变化的一氧化碳 (DLco) 以及分析我们建立的 12 种炎症生物标志物 加利福尼亚州旧金山和乌干达坎帕拉的队列研究，以更好地描述与艾滋病毒相关的肺部疾病 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特征 PWH 中的肺功能障碍。此外，在我们的试点数据分析中，我们发现发生这种情况的几率增加了四倍多 与感染艾滋病毒的男性相比，感染艾滋病毒的女性年龄较大，这一差异在女性和男性之间未见 没有艾滋病毒，表明潜在的艾滋病毒特异性性别差异，这对我们的研究具有重要影响 对感染艾滋病毒和未感染艾滋病毒的人的老年的了解。通过本补充，我们将解决是否存在 在我们的乌干达队列中，通过添加性激素和 性别分层的生物标志物。该项目将是此类项目中的第一个：（1）评估性别差异 在国际环境下，肺活量测定法和 DLco 在 PWH 中的应用（目标 1）； (2) 将肺活量测定法和 DLco 与性别进行比较 分层生物标志物（目标 2）； (3) 通过 性激素的测量（目标 3）。该补充提案涉及 ORWH 战略中的三个 通过添加关注性别差异的样本来实现目标（战略目标 1、2 和 4）。应该 感染艾滋病毒的女性的某些生物标志物、生育年龄和老年之间存在关系，这可能 为女性肺功能障碍性别差异的潜在机制提供重要见解 无论是否患有艾滋病毒，均可用于确定女性的性别特异性筛查和治疗目标 全世界。