Mechanisms & risk factors of chronic lung disease in HIV+ adolescents in Nairobi

机制

• 批准号: 10467934
• 负责人: Engi Farouk Attia
• 金额: $ 7.91万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10467934
• 关键词: 2019-nCoV; Administrative Supplement; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Aerosols; Air Pollution; Biological Markers; Bronchiolitis; COVID-19; COVID-19 pandemic; COVID-19 testing; COVID-19 vaccination; Catchment Area; Chest; Child; Chronic; Chronic lung disease; Clinical; Clinical Data; Communicable Diseases; Complex; Complication; Coughing; Country; Data; Data Collection; Data Set; Development; Diagnosis; Disease Progression; Exposure to; Forced expiratory volume function; Funding; Future; Geography; Growth; Growth and Development function; HIV; HIV Infections; Immune System Diseases; Immunologic Markers; Impairment; Income; Inflammation; Infrastructure; Inhalation Exposure; Intervention; Kenya; Light; Literature; Longitudinal Studies; Lung; Lung diseases; Lung infections; Machine Learning; Measures; Mosaicism; Natural History; Parents; Participant; Pathway interactions; Pattern; Pediatric HIV/AIDS Cohort Study; Phenotype; Population; Positioning Attribute; Procedures; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Pathology; Research; Resolution; Resources; Respiratory Signs and Symptoms; Risk; Risk Factors; Role; SARS-CoV-2 infection; Safety; Schedule; Serology; Serum; Spirometry; Statistical Data Interpretation; Testing; Therapeutic Intervention; Time; United States National Institutes of Health; Visit; Vulnerable Populations; Work; X-Ray Computed Tomography; antibody test; attenuation; base; chest computed tomography; cohort; environmental tobacco smoke; experience; fine particles; follow-up; immune activation; innovation; insight; low and middle-income countries; lung maturation; novel; perinatal HIV; personal protective equipment; preventive intervention; primary outcome; pulmonary function; respiratory; young adult

PROJECT SUMMARY/ABSTRACT As increasing numbers of children with HIV are surviving to adolescence in low- and middle-income countries, chronic lung disease (CLD) has emerged as an important but poorly understood complication amongst adolescents and young adults living with HIV (ALWH). In the ongoing, longitudinal BREATHE II Study (K23 HL129888, PI Attia) in Nairobi, Kenya, 19% of 162 ALWH have abnormal spirometry compared to 11% of 162 uninfected participants; 59% of ALWH have ≥1 abnormality on high-resolution chest CT scan, with mosaic attenuation among the most common. Chronic respiratory symptoms are also highly prevalent among 62% of ALWH and 49% of uninfected participants. HIV is independently associated with impaired lung function, and risk factors for impaired spirometry among ALWH include inhaled exposures, such as secondhand smoke and ambient fine particulate matter, as well as growth deficits. Objectives of the K23 research include: examining differences in risk factors and mechanisms of CLD progression over time; determining the role of HIV infection on change in lung function over time, considering the complex interplay with other risk factors; and, evaluating whether biomarkers of chronic immune activation and inflammation are associated with diminished lung function growth over time. However, in light of the COVID-19 pandemic, these longitudinal studies have been halted for safety reasons. As these studies can now resume with added precautions, an Administrative Supplement to this K23 will provide essential resources for the following Aims: 1) complete longitudinal lung function and clinical data collection to conduct planned analyses as proposed in the parent K23; 2) add testing for COVID-19 both to mitigate risk of potential spread of SARS-CoV-2 through spirometry (rapid PCR test) and to examine the role of COVID-19 infection on lung function growth and development (serologic antibody test). The indispensable support of this Supplement will maintain the BREATHE II cohort, a unique and innovative resource for understanding CLD progression among ALWH, especially those with perinatal HIV acquisition, compared to demographically similar uninfected participants from the same geographic catchment area in the context of COVID-19. This cohort includes a dataset of chest CTs that is larger than in any published literature to date. Serum for biomarker analysis (currently underway) has the potential to inform mechanistic pathways of CLD. The study infrastructure is already supporting implementation of sub-studies to obtain quantitative measures of air pollution exposure and to compare CLD in BREATHE II to a cohort of ALWH in a high-income setting, and is a well-positioned platform to support future sub-studies. Findings of this research will provide critical data for informing R01-level research to investigate novel insights into the pathophysiologic mechanisms of CLD progression in ALWH in resource-limited settings, shedding light on risk factors and mechanisms that can be targeted by preventative and therapeutic interventions to mitigate the burden of CLD.

项目摘要/摘要 随着艾滋病毒越来越多的儿童在低收入和中等收入国家中生存， 慢性肺病（CLD）已成为重要但知之甚少的并发症 青少年和艾滋病毒（ALWH）的年轻人。在正在进行的纵向呼吸II研究中（K23 肯尼亚内罗毕的HL129888，PI ATTIA），162 ALWH的19％具有异常的肺活量测定法 未感染的参与者；在高分辨率的胸部CT扫描中，有59％的ALWH绝对具有≥1的绝对功率，并带有马赛克 最常见的衰减。慢性呼吸道症状也很普遍 ALWH和49％的未感染参与者。 HIV与肺功能受损独立相关，并且 ALWH中肺活量测量受损的危险因素包括包括暴露，例如二手烟和 环境良好的特定物质以及增长不足。 K23研究的目标包括：检查 随着时间的流逝，CLD进展的危险因素和机制的差异；确定HIV感染的作用 考虑到与其他风险因素的复杂相互作用，肺功能随着时间的变化而变化；并评估 慢性免疫激活和炎症的生物标志物是否与肺部降低有关 随着时间的推移功能增长。然而，鉴于199年的大流行，这些纵向研究已经 出于安全原因停止。由于这些研究现在可以通过额外的预防措施恢复，因此 对此K23的补充将为以下目的提供基本资源：1）完整的纵向肺 功能和临床数据收集以进行父k23中提出的计划分析； 2）添加测试 对于COVID-19，既可以减轻SARS-COV-2通过肺活量测定法（快速PCR测试）和 检查Covid-19感染对肺功能生长和发育的作用（血清学抗体测试）。 这种补充的必不可少的支持将保持呼吸II队列，这是一个独特而创新的 理解ALWH中CLD进展的资源，尤其是那些患有围产期HIV的人， 与来自人口统计学相似的未感染的参与者相比 Covid-19的背景。该队列包含一个比任何已发表文献大的胸部CT数据集 迄今为止。生物标志物分析的血清（目前正在进行）有可能为机械途径提供信息 Cld。研究基础设施已经支持实施子研究以获得定量 空气污染暴露的度量并将呼吸II中的CLD与高收入中的ALWH进行比较 设置，是一个良好的平台，可以支持未来的子培训。这项研究的结果将提供 用于告知R01级研究的关键数据，以研究对病理生理学的新见解 在资源有限的设置中，ALWH中CLD进展的机制，阐明了风险因素和 可以通过预防和治疗干预措施来靶向的机制来减轻CLD的燃烧。