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

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• 批准号: 9270386
• 负责人: Engi Farouk Attia
• 金额: $ 18.88万
• 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/9270386
• 关键词: Accounting; Adolescence; Adolescent; Adult; Advisory Committees; Age; Award; 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 Sciences; Clinical Trials; Clinical Trials Network; 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; Infection; Inflammation; Institutes; Institution; Interleukin-6; International; Intervention; K-Series Research Career Programs; Kenya; Laboratories; Learning; Light; Longitudinal Studies; Lung; Lung diseases; 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; Translational Research; 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.

项目摘要/摘要 候选人：阿蒂亚博士的长期目标是在全球范围内改善肺部健康，进行临床研究和试验 在慢性肺部疾病中，重点是艾滋病毒的作用和其他风险因素影响 肺部疾病的病理生理和临床过程。本申请中提出的研究基于她 先前的工作，发现慢性呼吸症状和异常的患病率明显更高 在资源有限的环境中，与成年人相比，艾滋病毒+青少年之间的肺活量测定法。这个K23职业 发展奖将为阿蒂亚博士提供基本的研究培训，以支持她成为 肺部疾病，艾滋病毒和全球健康交叉点的独立研究者。通过这个项目， 阿蒂亚博士将实现她获得以下学习中概述的专业知识的直接目标 目标：1）在青少年的肺部生长测量和分析中培训； 2）设计和 纵向研究的实施； 3）对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学方法； 5）负责执行研究活动 国际环境。这些目标将通过一个结构化的职业发展计划来实现 纳入正式课程，由咨询委员会指导，并具有肺部集体专业知识 疾病和肺部生长，HIV，儿科，流行病学，生物统计学以及在临床中的使用 研究以及获得实践研究经验的保护时间。 环境：华盛顿大学（UW）的丰富学术环境是博士博士的理想场所 阿蒂亚（Attia）继续进行研究培训。 UW是一家杰出的生物医学研究机构 致力于促进有前途的研究人员的学术职业。 UW肺部和 重症监护医学以其临床研究培训轨道广泛认可，并提供智力 支持开发与其他调查人员合作所需技能的环境以及 取得学术成就。除了部门内提供的资源和支持外，Attia博士还将 也可以完全访问UW全球健康教学和专家的资源 教育（Tree）计划（由她的同事指导），该计划提供行政，临床，实验室 以及支持UW隶属于Coptic Hope的临床研究的数据库管理基础架构 肯尼亚内罗毕的传染病中心。阿蒂亚博士将在 通过该青少年获得和分析肺活量法作为衡量肺部生长和发育的量度 大学儿科和大学领导的多站点囊性纤维化临床试验网络的资源， 囊性纤维化疗法开发网络。阿蒂亚博士还将获得临床研究和 大学公共卫生学院和转化健康科学研究所的生物统计学支持 计划（UW的临床和转化科学奖计划）。 研究：阿蒂亚博士将研究患病率，亚型，风险因素和机制的差异 慢性肺部疾病，通过基线检测，并在2年内重复支气管扩张剂肺活量测定法 来自希望中心的150名HIV+青少年，而年龄和性别匹配的150个HIV控制。 在HIV+青少年中，将通过基线CT扫描进一步表征慢性肺部疾病。她 将确定HIV感染在基线和基线时慢性肺疾病表现的作用 随着时间的推移，肺功能的变化，考虑到与其他风险因素的复杂相互作用，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和生物标志物的严重程度是否 慢性免疫激活和炎症与慢性肺的患病率增加有关 疾病和肺功能随着时间的推移而降低。本应用程序中提出的研究是创新的 因为它表示第一项研究至1）直接表征慢性的流行病学和病理生理学 与在资源有限的环境中相比 与HIV+相比 青少年和3）确定慢性免疫激活，炎症和HIV的血清标记是否是否 严重程度与慢性肺部疾病有关，提供了潜在的机械见解。这一点 研究将为慢性肺的亚型和病理生理机制提供新的见解 在资源有限的环境中，艾滋病毒+青少年的疾病发展和进展，阐明了风险 可以通过预防和治疗干预措施来针对的因素和机制来减轻 慢性肺部疾病的负担。