The Role of Alcohol Use in Lung Disease After Treatment for Active TB Disease Among Persons Living with HIV

修改项目摘要/摘要部分 结核病（TB）是单一传染源导致死亡的主要原因，也是艾滋病毒感染者（PWH）死亡的主要原因。据估计，每年有850万结核病患者被治愈，但许多人没有恢复完全健康。在完成肺结核治疗的人中，多达一半的人患有结核病后肺部疾病，这是一组诊断不足的肺功能缺陷。肺结核治疗完成时的肺功能缺损是肺结核后一年内肺部疾病严重程度的最强预测因子。酒精和艾滋病毒与肺免疫功能障碍有关，酒精使用与结核病诊断延迟有关，增加了活动性结核病期间肺损伤的风险。然而，目前尚不清楚饮酒是否与PWH的结核病后肺部疾病有关。我们假设危险饮酒增加了PWH患者对结核病后肺部疾病的易感性。我们的目的是调查危险饮酒（酒精使用障碍识别测试[AUDIT] ≥8）作为PWH患者结核病后肺部疾病的可改变风险因素。为了实现这一目标，我们提出了一个为期18个月的观察研究，200 PWH完成肺结核治疗在姆巴拉拉，乌干达。我们将评估以下结核病后肺部疾病结局：功能性运动能力（通过6分钟步行距离评估的主要结局）、肺生理学（肺功能检查）、解剖学（CT扫描）和肺部感染。主要接触是过去一年的危险饮酒。二级酒精测量将包括30天时间轴随访（基于酒精使用回忆的方法）和磷脂酰乙醇（PEth;近期酒精使用的生物标志物）。我们的专业知识涵盖酒精使用，艾滋病毒，结核病，肺病，流行病学和生物统计学。我们的主要目标（目标1a）是确定过去一年危险饮酒与结核病后肺部疾病之间的关系。在目标1b中，我们评估了过去一个月大量饮酒与结核病后肺部疾病随时间进展的关系。在目标1c中，我们探讨了吸烟是否改变了过去一个月大量饮酒与结核病后肺部疾病随时间进展的关系。目标1b和1c中的重度饮酒通过时间轴随访定义为每周饮酒≥7次（女性）或每周饮酒≥14次（男性）或PEth>200 ng/mL。在目标2中，我们将定性评估可以改善接受结核病治疗的PWH的药物行为酒精和吸烟干预措施的因素。我们会在结核病治疗期间或之后，深入访问24名威尔斯亲王医院的病人，以及12名结核病医护人员。影响：我们将确定PWH中酒精使用与结核病后肺部疾病的关系。我们的定量和定性数据将为未来的工作奠定基础，以定制酒精和吸烟干预措施，以改善艾滋病毒/结核病合并感染的长期健康状况。

Modified Project Summary/Abstract Section Tuberculosis (TB) is the leading cause of death from a single infectious agent and the leading cause of death in people with HIV (PWH). An estimated 8.5 million people with TB are cured every year but many do not return to full health. Up to half of those completing treatment for pulmonary TB have post-TB lung disease, a disabling under-diagnosed group of lung deficits. Lung deficits at TB treatment completion are the strongest predictors of post-TB lung disease severity up to a year later. Alcohol and HIV are associated with lung immune dysfunction and alcohol use is associated with delayed TB diagnosis, increasing the risk of lung injury during active TB disease. However, it is not known whether alcohol use is associated with post-TB lung disease in PWH. We hypothesize that hazardous drinking increases susceptibility to and worsens post-TB lung disease in PWH. Our objective is to investigate hazardous drinking (Alcohol Use Disorders Identification Test [AUDIT] ≥8) as a modifiable risk factor for post-TB lung disease in PWH. To achieve this, we propose an 18- month observational study of 200 PWH completing pulmonary TB treatment in Mbarara, Uganda. We will evaluate the following post-TB lung disease outcomes: functional exercise capacity (primary outcome assessed by 6-minute walk distance), lung physiology (pulmonary function tests), anatomy (CT scan), and lung infections. The primary exposure is past-year hazardous drinking. Secondary alcohol measures will include 30- day Timeline Followback (calendar-based method of alcohol use recall) and phosphatidylethanol (PEth; a biomarker of recent alcohol use). Our expertise spans alcohol use, HIV, TB, pulmonology, epidemiology, and biostatistics. Our primary aim (Aim 1a) is to determine the relationship between past-year hazardous drinking and post-TB lung disease. In Aim 1b we assess the association of past-month heavy drinking and post-TB lung disease progression over time. In Aim 1c we explore whether smoking modifies the association of past- month heavy drinking and post-TB lung disease progression over time. Heavy drinking in Aims 1b and 1c is defined by Timeline Followback as ≥7 drinks/week (women) or ≥14 drinks/week (men) or PEth>200 ng/mL. In Aim 2, we will qualitatively evaluate factors that can improve tailoring of pharmaco-behavioral alcohol and smoking interventions in PWH receiving TB treatment. We will conduct in-depth interviews with 24 PWH during or after TB treatment and 12 TB healthcare providers. IMPACT: We will determine the association of alcohol use and post-TB lung disease in PWH. Our quantitative and qualitative data will lay the foundation for future work to tailor alcohol and smoking interventions to improve long-term health in HIV/TB co-infection.