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: 10541238
• 负责人: Engi Farouk Attia
• 金额: $ 8.15万
• 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/10541238
• 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; 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; Intervention; Intervention Studies; Kenya; Knowledge; Lung; Lung diseases; Measures; Methods; Modeling; 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; chest computed tomography; cohort; comorbidity; density; disorder subtype; emerging adult; imaging study; immune activation; improved; innovation; insight; lung health; metabolomics; mosaic; 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 慢性肺病（CLD）在全球范围内出现是一种重要但尚不完全理解的合并症 在当代抗逆转录病毒疗法时代的艾滋病毒（YLWH）的青年中。在YLWH中，Cld 包括多种亚型，包括闭塞性支气管炎，支气管扩张和哮喘。这 异质性增加了使用临床数据（例如症状和）表征CLD亚型的复杂性 肺活量测定法可能重叠。在正在进行的纵向呼吸II研究（K23 HL129888）中 YLWH和其他胸部CT成像研究中的161个胸部CT在YLWH中，胸部CT异常是 常见且经常伴随的。 YLWH中的研究尚未完全纳入此程度的异质性 在检查或识别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）迅速成为临床和 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中的亚型表征，预后和结果预测。呼吸II研究，合并 借助早期的飞行员工作，提供了一个独特的机会，可以应用Quontct扩展和完善CLD亚型 迄今为止，最大的胸部CT成像队列。量定指标包括静态和功能性肺 密度，质地类别（例如地面玻璃，超韧性，网状）的密度，实质受累％和 气道壁厚。这项研究的总体目标是确定相关的临床特征 用YLWH中的量定指标定义的肺异常，并确定这些量定指标是否是 可以识别随着时间的推移，与肺功能生长轨迹相关的CLD的亚型。此外 整个肺场的低剂量灵感和呼气CT扫描，可用数据包括重复前和 支气管扩展器的肺活量测定法，以呼吸道为重点的问卷和身体检查数据以及基线 血清炎症生物标志物。该项目将有效利用这些严格收集的数据，并添加 量定分析可提供新颖，创新的客观指标，以改善YLWH中的CLD表征。 研究团队在与HIV相关的肺部疾病，流行病学，数据科学和Quontct方面具有集体专业知识， 确保成功完成以下目的：1）确定基线临床特征，包括 肺活量测定法，与肺异常相关的HIV疾病严重程度和血清生物标志物的定义 通过YLWH中的量定指标； 2）使用无监督的聚类方法识别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的表征 使用目标，与操作员无关，定量测量可以改善CLD亚型的识别 在ylwh中。发现可以提供有关YLWH中CLD病理生理机制的见解，并且可以 告知有针对性的，以患者为中心的干预研究，以在该人群中实施基于证据的实践。