MACS/WIHS -CCS-Supplement

项目摘要 2022财年OAR战略基金被要求对以下关系进行详细调查： 口腔微生物组、免疫反应和HIV对慢性阻塞性肺疾病（COPD）的影响。 COPD，包括气道阻塞和肺气肿，是一个日益严重的健康问题， 艾滋病毒（PWH），即使在抗逆转录病毒治疗（ART）的当前时代。我们的初步数据表明， 口腔微生物组与肺功能相关，但我们缺乏对口腔微生物组作用的详细了解。 特别是微生物群落和潜在的机制支撑的协会， 目前阻碍了干预战略的制定。我们将利用口腔数据，微生物组 分析，血液标本和肺功能测量已经收集了整个 在访视102和103中进行MWCCS，以分析口腔健康与口腔 微生物组对肺功能的影响我们还将测量外周细胞因子、炎症因子、 反应和口腔环境，以评估微生物组与 肺健康这些研究将在所有完成肺功能检查的个体中进行。 跨MWCCS的功能测试。然后，我们将进行详细的口腔评估，并收集微生物 从参与者的一个子集中的多个口腔龛中提取样本，以更好地描绘特定的 口腔健康成分和肺功能。使用一种新技术来识别 免疫球蛋白结合的细菌和真菌，我们将确定驱动宿主反应的关键微生物， 与COPD有关。这些调查将确定可能改变的目标， PWH中的COPD。 我们将讨论NIH高优先级艾滋病指定的主题：1）一个共同的和高负担的艾滋病毒- 2）肺部疾病专家之间的跨学科合作， 微生物组，牙科医学和分析; 3）艾滋病毒的差异，考虑到社会决定因素的影响， 健康对肺功能和口腔健康的影响; 4）交叉科学的基本发现;以及5） 培养下一代艾滋病研究人员。 这些调查将建立在MWCCS以前进行的研究的基础上， HIV相关肺部疾病的新机制，有可能开发新的干预措施， 调节口腔微生物组以改善肺功能。

PROJECT ABSTRACT FY 2022 OAR Strategic Funds are requested to perform a detailed investigation of the relationship of the oral microbiome, immune response, and HIV to chronic obstructive pulmonary disease (COPD). COPD, including airway obstruction and emphysema, is an increasing health problem in people with HIV (PWH) even in the current era of antiretroviral therapy (ART). Our preliminary data suggest that the oral microbiome is associated with lung function, but we lack a detailed understanding of the role of particular microbial communities and the potential mechanisms underpinning the association, which currently impedes development of intervention strategies. We will utilize oral data, microbiome analyses, blood specimens, and pulmonary function measures already being collected throughout MWCCS in visits 102 and 103 in order to analyze the relationship of oral health and the oral microbiome to lung function. We will also perform measurements of peripheral cytokines, inflammatory responses, and the oral cavity environment to assess potential mechanisms linking the microbiome to lung health. These investigations will be performed in all individuals who have completed pulmonary function testing across MWCCS. We will then perform detailed oral evaluations and collect microbial samples from multiple oral niches in a subset of participants to better delineate relationships of specific oral health components and lung function at Pitt and UNC. Using a novel technique to identify immunoglobulin-bound bacteria and fungi, we will identify key microbes that drive host response and are related to COPD. These investigations will identify potentially modifiable targets contributing to COPD in PWH. We will address NIH high priority AIDS-designated topics of: 1) a common and high-burden HIV- associated comorbidity; 2) interdisciplinary collaborations among experts in pulmonary disease, microbiome, dental medicine, and analytics; 3) disparities in HIV given impact of social determinants of health on both lung function and oral health; 4) fundamental discovery in cross-cutting science; and 5) training the next generation of HIV investigators. These investigations will build on the previous research conducted by the MWCCS and provide insight into a novel mechanism of HIV-associated lung disease with potential to develop new interventions to modulate the oral microbiome to improve pulmonary function.