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

描述青年艾滋病毒感染者慢性肺部疾病的特征：定量胸部 CT 分析

• 批准号: 10402042
• 负责人: Engi Farouk Attia
• 金额: $ 8.84万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402042
• 关键词: Adolescence; Air; Area; Asthma; Biological Markers; Bronchiectasis; Bronchiolitis; Bronchodilator Agents; CD8B1 gene; Categories; Cells; Characteristics; Chest; Child; Chronic lung disease; Clinical; Clinical Data; Clinical Research; Complication; Data; Data Science; Disease Progression; Dose; Ensure; Epidemiology; Evaluation; Evidence based practice; Forced expiratory volume function; Genomics; Glass; Goals; Growth; HIV; Heterogeneity; Image; Impairment; Inflammation; Inflammatory; Interleukin-6; Intervention; Intervention Studies; Kenya; Knowledge; Lung; Lung diseases; Measures; Methods; Modeling; Mosaicism; Persons; Population; Positioning Attribute; Proteomics; Pulmonary Function Test/Forced Expiratory Volume 1; Questionnaires; Research; Running; Scanning; Serum; Serum Markers; Severities; Severity of illness; South Africa; Spirometry; Structure of parenchyma of lung; Symptoms; Texture; Thick; Time; Visual; Vital capacity; Work; X-Ray Computed Tomography; Youth; airway obstruction; antiretroviral therapy; attenuation; base; chest computed tomography; cohort; comorbidity; density; disorder subtype; emerging adult; epidemiologic data; imaging study; immune activation; improved; innovation; insight; lung health; metabolomics; novel; outcome prediction; patient oriented; prognostication; pulmonary function; radiological imaging; radiologist; respiratory; tool; ventilation

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.

项目摘要 慢性肺疾病（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疗法时代，艾滋病毒感染青年（YLWH）的人数。在YLWH、CLD 包括多种亚型，包括闭塞性细支气管炎、支气管扩张和哮喘。这 异质性增加了使用临床数据（如症状和 肺量测定可能会重叠在正在进行的纵向BREATHE II研究（K23 HL 129888）中， 在YLWH的161例胸部CT和YLWH的其他胸部CT成像研究中，胸部CT异常是 共同的并且经常是伴随的。在YLWH中的研究没有完全纳入这种异质性程度 在检查或鉴定CLD亚型时，限制了对YLWH中CLD类型的理解。胸部 用于CLD评估的定量CT方法（quantCT）作为临床和 研究工具。与胸部CT和临床特征的视觉评估相比，quantCT可以改善 CLD的亚型特征、分类和结果预测。呼吸II研究，结合 与早期的试点工作，提供了一个独特的机会，应用quantCT扩大和完善CLD亚型， YLWH迄今为止最大的胸部CT成像队列。QuantCT指标包括静态和功能性肺 密度，按纹理类别划分的实质受累百分比（例如，毛玻璃样、透亮、网状）， 气道壁厚度本研究的总体目标是确定与此相关的临床特征， 在YLWH中由quantCT指标定义的肺部异常，并确定这些quantCT指标是否 可以识别CLD的亚型，这些亚型与肺功能随时间的增长轨迹相关。除了 整个肺野的低剂量吸气和呼气CT扫描，可用数据包括重复的术前和 使用支气管扩张剂后的肺功能测定、以治疗为重点的问卷调查和体格检查数据，以及基线 血清炎症生物标志物。该项目将有效地利用这些严格收集的数据， quantCT分析，以提供新的，创新的，客观的指标，以改善CLD表征在YLWH。 该研究小组在艾滋病毒相关肺部疾病、流行病学、数据科学和quantCT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 肺功能测定、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 2）使用无监督聚类方法识别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表征 使用客观的、独立于操作者的定量测量可以改善CLD亚型的识别 在YLWH中。研究结果可以提供深入了解CLD在YLWH的病理生理机制， 为有针对性的、以患者为中心的干预研究提供信息，以在这一人群中实施循证实践。