Characterizing chronic lung disease in youth living with HIV: quantitative chest CT analyses

项目总结 慢性肺病(CLD)已成为全球范围内一种重要但尚未完全了解的合并症 在当代抗逆转录病毒治疗时代，青年艾滋病毒携带者(YLWH)。在YLWH、CLD 包括多种亚型，包括闭塞性毛细支气管炎、支气管扩张症和哮喘。这 异质性增加了使用临床数据来表征CLD亚型的复杂性，例如症状和 可以重叠的肺活量测定仪。在正在进行的纵向呼吸II研究(K23 HL129888)中，获得了 161例青少年儿童胸部CT检查及青少年儿童医院其他胸部CT检查中， 常见的，经常伴随的。青瓦台的研究还没有完全纳入这种程度的异质性。 在检查或鉴定CLD亚型时，限制了YLWH对CLD类型的了解。胸部 定量CT方法(QuantCT)用于CLD的评估正迅速获得重视，因为临床和 研究工具。与胸部CT的视觉评估和临床特征相比，QuantCT可以提高 慢性腰椎病的亚型特征、预后和预后预测。呼吸II研究，合并 通过早期的试点工作，提供了一个独特的机会来应用QuantCT来扩展和完善CLD子类型 YLWH迄今为止最大的胸部CT成像队列。QuantCT指标包括静态肺和功能肺 密度，按纹理类别划分的实质受累百分比(例如，磨砂玻璃、高透明度、网状结构)和 气道壁厚度。这项研究的总体目标是确定相关的临床特征 YLWH的QuantCT指标定义的肺部异常并确定这些QuantCT指标 可以识别与肺功能随时间增长轨迹相关的慢性阻塞性肺疾病的亚型。除了……之外 低剂量吸气和呼气CT扫描整个肺野，可用的数据包括重复前和 支气管扩张剂治疗后的肺活量、以呼吸为重点的问卷调查和体检数据，以及基线 血清炎性生物标志物。该项目将有效地利用这些严格收集的数据并添加 QuantCT分析，提供新颖、创新、客观的指标，以改善青光眼的CLD特征。 研究小组在艾滋病毒相关肺部疾病、流行病学、数据科学和量子CT方面拥有集体专业知识， 确保成功完成以下目标：1)确定基线临床特征，包括 肺活量测定、HIV疾病严重程度标志物和与肺部异常相关的血清生物标志物 通过YLWH中的QuantCT指标；2)使用非监督聚类方法识别CLD亚型，并确定 这些亚型是否与肺功能生长轨迹相关。胸部CT的特征分析 使用客观的、不依赖于操作员的定量措施可能会改善CLD亚型的识别 其中YLWH。这些研究结果可以为青光眼和CAN的CLD的病理生理机制提供深入的认识 告知有针对性的、以患者为中心的干预研究，以便在这一人群中实施循证实践。

PROJECT SUMMARY Chronic lung disease (CLD) has emerged globally as an important but incompletely understood comorbidity among youth living with HIV (YLWH) in the contemporary antiretroviral therapy era. Among YLWH, CLD encompasses multiple subtypes, including obliterative bronchiolitis, bronchiectasis and asthma. This heterogeneity adds complexity to characterizing CLD subtypes using clinical data such as symptoms and spirometry that can overlap. In the ongoing, longitudinal BREATHE II Study (K23 HL129888), which obtained 161 chest CTs among YLWH and in other chest CT imaging studies in YLWH, chest CT abnormalities are common and often concomitant. Studies among YLWH have not fully incorporated this degree of heterogeneity in examining or identifying CLD subtypes, limiting understanding of the types of CLD among YLWH. Chest quantitative CT methods (quantCT) for CLD assessment are rapidly gaining importance as clinical and research tools. Compared to visual assessment of chest CT and clinical characteristics, quantCT can improve subtype characterization, prognostication and outcome prediction in CLDs. The BREATHE II Study, combined with earlier pilot work, provides a unique opportunity to apply quantCT to expand and refine CLD subtyping in the largest chest CT imaging cohort in YLWH to date. QuantCT metrics include static and functional lung density, % parenchymal involvement by texture categories (e.g., ground glass, hyperlucency, reticulation) and airway wall thickness. Overall objectives of this research are to determine clinical characteristics associated with lung abnormalities defined by quantCT metrics in YLWH and determine whether these quantCT metrics can identify subtypes of CLD that are associated with lung function growth trajectories over time. In addition to low-dose inspiratory and expiratory CT scans of the entire lung fields, available data include repeat pre- and post-bronchodilator spirometry, respiratory-focused questionnaires and physical exam data, and baseline serum inflammatory biomarkers. This project will efficiently leverage these rigorously collected data and add quantCT analyses to provide novel, innovative, objective metrics to improve CLD characterization in YLWH. The study team has collective expertise in HIV-related lung disease, epidemiology, data science and quantCT, ensuring successful completion of the following Aims: 1) Determine baseline clinical characteristics, including spirometry, markers of HIV disease severity and serum biomarkers associated with lung abnormalities defined by quantCT metrics in YLWH; 2) Identify CLD subtypes using unsupervised clustering methods, and determine whether these subtypes are associated with lung function growth trajectories. Characterization of chest CT using objective, operator-independent, quantitative measures may improve identification of CLD subtypes among YLWH. Findings can provide insights into pathophysiologic mechanisms of CLD in YLWH and can inform targeted, patient-centered intervention studies to implement evidence-based practices in this population.