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

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• 批准号: 9431238
• 负责人: Engi Farouk Attia
• 金额: $ 18.64万
• 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 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9431238
• 关键词: Accounting; Adolescence; Adolescent; Adult; Advisory Committees; Age; Biological Markers; Biomedical Research; Biometry; Biostatistical Methods; Bronchiolitis; Bronchodilator Agents; C-reactive protein; CD14 gene; Chest; Child; Chronic; Chronic lung disease; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Network; Clinical and Translational Science Awards; Communicable Diseases; Complex; Complication; Coughing; Country; Critical Care; Cystic Fibrosis; Data; Data Base Management; Data Collection; Development; Development Plans; Diagnosis; Diagnostic; Disease; Education; Educational process of instructing; Enrollment; Environment; Epidemiologic Methods; Epidemiology; Etiology; Exposure to; Forced expiratory volume function; Functional disorder; Future; Goals; Growth; Growth and Development function; HIV; HIV Infections; HIV diagnosis; Health; Height; IL6 gene; Immune system; Immunologic Markers; Income; Inflammation; Institutes; Institution; Interleukin-6; International; Intervention; K-Series Research Career Programs; Kenya; Laboratories; Learning; Light; Longitudinal Studies; Lung; Lung diseases; Lung infections; Malnutrition; Measurement; Measures; Medicine; Mentors; Modality; Monitor; Oxygen; Patients; Pattern; Pediatric epidemiology; Persons; Pilot Projects; Population; Positioning Attribute; Prevalence; Preventive Intervention; Procedures; Production; Prospective Studies; Public Health Schools; Publishing; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Pathology; Quality Control; Questionnaires; Records; Research; Research Activity; Research Infrastructure; Research Personnel; Research Training; Resources; Respiratory Signs and Symptoms; Respiratory physiology; Risk; Risk Factors; Role; Serum; Serum Markers; Severities; Site; Smoking; Spirometry; Sputum; Standardization; Structure; Systems Development; Therapeutic Intervention; Time; Training; Universities; University resources; Viremia; Vulnerable Populations; Washington; Work; X-Ray Computed Tomography; Zimbabwe; antiretroviral therapy; base; burden of illness; career; career development; chest computed tomography; cigarette smoking; critical period; design; disorder subtype; experience; global health; immune activation; implementation research; improved; innovation; insight; low and middle-income countries; lung maturation; modifiable risk; novel; pediatric department; programs; sex; skill acquisition; success; therapeutic development; translational health science

PROJECT SUMMARY/ABSTRACT Candidate: Dr. Attia's long-term goal is to improve lung health globally, conducting clinical research and trials in chronic lung diseases, with a focus on the role of HIV and other risk factors in influencing the pathophysiology and clinical course of lung disease. The research proposed in this application builds on her previous work, which found a significantly greater prevalence of chronic respiratory symptoms and abnormal spirometry among HIV+ adolescents compared to adults in a resource-limited setting. This K23 Career Development Award will provide Dr. Attia with essential research training to support her goal of becoming an independent investigator at the intersection of pulmonary disease, HIV and global health. Through this project, Dr. Attia will accomplish her immediate goals of attaining the expertise outlined in the following learning objectives: 1) training in measurement and analysis of lung growth in adolescents; 2) design and implementation of longitudinal studies; 3) quality control and monitoring of prospective studies; 4) advanced biostatistical methods to analyze complex data; and 5) responsible implementation of research activities in an international setting. These objectives will be achieved through a structured career development plan that incorporates formal coursework, mentoring by an advisory committee with collective expertise in pulmonary disease and lung growth, HIV, pediatrics, epidemiology, biostatistics and the use of biospecimens in clinical research, as well as protected time to gain practical research experience. Environment: The rich academic environment at the University of Washington (UW) is an ideal place for Dr. Attia's continued research training. UW is an outstanding biomedical research institution with a strong commitment to promoting the academic careers of promising investigators. The UW Division of Pulmonary and Critical Care Medicine is widely recognized for its Clinical Research Training Track and offers an intellectual environment that supports development of the skills necessary to collaborate with other investigators and achieve academic success. In addition to the resources and support provided within the Division, Dr. Attia will also have full access to the resources of the UW Department of Global Health Teaching, Research and Expert Education (TREE) program (directed by her co-mentor), which provides the administrative, clinical, laboratory and database management infrastructure that supports clinical research at the UW-affiliated Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. Dr. Attia will receive directed training and mentoring in obtaining and analyzing spirometry in adolescents as a measure of lung growth and development through the resources of the UW Department of Pediatrics and the UW-led multi-site cystic fibrosis clinical trials network, Cystic Fibrosis Therapeutics Development Network. Dr. Attia will also have access to clinical research and biostatistical support through the UW School of Public Health and the Institute of Translational Health Sciences program (the Clinical and Translational Science Award program at UW). Research: Dr. Attia will examine differences in the prevalence, subtypes, risk factors and mechanisms of chronic lung disease, detected by baseline and repeat pre- and post-bronchodilator spirometry over 2 years in 150 HIV+ adolescents from the Hope Center compared to 150 HIV- controls, block-matched on age and sex. Among HIV+ adolescents, chronic lung disease will be further characterized with baseline chest CT scans. She will determine the role of HIV infection on the manifestations of chronic lung disease at baseline and the change in lung function over time, considering the complex interplay with other risk factors including malnutrition and indoor biofuel burning. She will also evaluate whether severity of HIV disease, and biomarkers of chronic immune activation and inflammation are associated with an increased prevalence of chronic lung disease and diminished lung function growth over time. The research proposed in this application is innovative because it signifies the first study to 1) directly characterize the epidemiology and pathophysiology of chronic lung disease in HIV+ compared to HIV- adolescents in a resource-limited setting, 2) ascertain risk factors associated with change in lung function over time, assessed by repeated spirometry, in HIV+ compared to HIV- adolescents, and 3) determine whether serum markers of chronic immune activation, inflammation and HIV severity are associated with chronic lung disease, providing potential mechanistic insights. Findings of this research will provide novel insights into the subtypes and pathophysiologic mechanisms of chronic lung disease development and progression in HIV+ adolescents 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 chronic lung disease.

项目概要/摘要 候选人：Attia博士的长期目标是改善全球肺部健康，进行临床研究和试验 慢性肺部疾病，重点关注艾滋病毒和其他危险因素在影响肺部疾病方面的作用 肺部疾病的病理生理学和临床过程。本申请中提出的研究建立在她的基础上 之前的工作发现慢性呼吸道症状和异常的患病率明显更高 与资源有限环境中的成年人相比，艾滋病毒+青少年的肺活量测定。 K23职业生涯 发展奖将为 Attia 博士提供必要的研究培训，以支持她成为一名 肺部疾病、艾滋病毒和全球健康交叉领域的独立调查员。通过这个项目， Attia 博士将实现她的近期目标，即获得以下学习中概述的专业知识 目标：1) 青少年肺部生长测量和分析培训； 2）设计和 实施纵向研究； 3）前瞻性研究的质量控制和监测； 4）高级 分析复杂数据的生物统计方法； 5) 负责任地开展研究活动 国际化的环境。这些目标将通过结构化的职业发展计划来实现，该计划 包含正式的课程作业，由具有肺病集体专业知识的咨询委员会提供指导 疾病和肺部生长、艾滋病毒、儿科、流行病学、生物统计学以及生物样本在临床中的使用 研究，以及获得实际研究经验的保护时间。 环境：华盛顿大学（UW）丰富的学术环境是博士的理想之地。 阿蒂亚的继续研究训练。 UW 是一所杰出的生物医学研究机构，拥有雄厚的实力 致力于促进有前途的研究人员的学术生涯。华盛顿大学肺科和 重症监护医学因其临床研究培训课程而受到广泛认可，并提供知识分子 支持发展与其他研究人员合作所需的技能的环境 取得学术成功。除了该部门提供的资源和支持外，阿蒂亚博士还将 还可以充分利用威斯康星大学全球健康教学、研究和专家系的资源 教育（TREE）计划（由她的共同导师指导），提供行政、临床、实验室 支持威斯康星大学附属科普特希望医院临床研究的数据库管理基础设施 肯尼亚内罗毕传染病中心。 Attia 博士将接受以下方面的定向培训和指导 通过以下方式获取和分析青少年的肺活量测定法，作为肺部生长和发育的衡量标准 华盛顿大学儿科和华盛​​顿大学领导的多站点囊性纤维化临床试验网络的资源， 囊性纤维化治疗开发网络。 Attia 博士还将获得临床研究和 通过华盛顿大学公共卫生学院和转化健康科学研究所提供的生物统计支持 计划（华盛顿大学的临床和转化科学奖计划）。 研究：Attia 博士将研究患病率、亚型、危险因素和机制的差异 慢性肺部疾病，通过基线检测并在 2 年内重复使用支气管扩张剂前和后肺活量测定 来自希望中心的 150 名 HIV 阳性青少年与 150 名 HIV 对照者进行了年龄和性别组块匹配。 在 HIV + 青少年中，慢性肺部疾病将通过基线胸部 CT 扫描进一步表征。她 将确定艾滋病毒感染对基线慢性肺病表现的作用以及 考虑到与其他危险因素的复杂相互作用，肺功能随时间的变化，包括 营养不良和室内生物燃料燃烧。她还将评估艾滋病毒疾病的严重程度和生物标志物是否 慢性免疫激活和炎症的增加与慢性肺病患病率的增加有关 随着时间的推移，疾病和肺功能发育减弱。本申请提出的研究具有创新性 因为它标志着第一项研究 1）直接表征慢性病的流行病学和病理生理学 在资源有限的环境中，与 HIV-青少年相比，HIV+ 青少年的肺部疾病，2) 确定危险因素 与 HIV- 相比，HIV+ 与肺功能随时间的变化相关，通过重复肺活量测定进行评估 青少年，以及 3) 确定是否存在慢性免疫激活、炎症和 HIV 的血清标志物 严重程度与慢性肺病相关，提供了潜在的机制见解。本次调查结果 研究将为慢性肺病的亚型和病理生理机制提供新的见解 资源有限环境中艾滋病毒+青少年的疾病发展和进展，揭示风险 预防和治疗干预措施可以针对的因素和机制，以减轻 慢性肺病的负担。