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

项目总结/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 在慢性肺部疾病中，重点关注HIV和其他危险因素在影响病理生理学中的作用 和肺部疾病的临床过程。在她的K23职业发展的资助扩展中提出的研究 该奖项建立在她以前和正在进行的工作基础上，这些工作证明了慢性肺部疾病的巨大负担。 在资源有限的环境中，艾滋病毒感染青少年中的艾滋病毒/艾滋病。这个扩展将提供阿提亚博士 有必要的保护时间来完成她的K23研究目标2和3的纵向分析，提交 R 01申请，并继续培训，以支持她成为一名独立调查员的目标， 肺部疾病、艾滋病毒和全球健康的交叉点。在延期期间，阿提亚医生将继续巩固 她的专长：1）青少年肺部生长分析培训; 2）先进的生物统计方法， 分析复杂的相关和缺失数据。这些目标将通过职业发展来实现 计划包括课程和由具有肺专业知识的咨询委员会持续指导 疾病和肺生长，艾滋病毒，流行病学，生物统计学，以及临床研究中生物标本的使用。 环境：华盛顿大学（UW）丰富的学术环境是博士的理想场所。 阿提亚的持续研究训练。UW是一个优秀的生物医学研究机构，具有强大的 致力于促进有前途的研究人员的学术生涯。UW肺科和 重症监护医学因其临床研究培训轨道而得到广泛认可，并提供了一个知识分子 环境，支持实现学术成功所需的技能的发展。作为 全球卫生教学，研究和专家教育计划的UW部门，Attia博士将有 全面访问支持行政、临床、实验室和数据库管理的资源 内罗毕的华盛顿大学附属科普特希望传染病中心的临床研究基础设施， 肯尼亚.她还将通过UW CTSA和公共卫生学院获得生物统计支持。 研究：在此扩展期间，Attia博士将研究亚型，风险因素和机制的差异 慢性肺部疾病，基于3-4年内获得的重复使用支气管扩张剂前后肺功能测定， 来自希望中心的161名艾滋病毒感染者与174名未感染艾滋病毒的青少年进行了比较。她将： 1)确定艾滋病毒对肺功能随时间变化的作用，考虑到与其他疾病的复杂相互作用， 风险因素，包括营养不良和室内生物燃料燃烧; 2）评估艾滋病毒的严重程度， 免疫激活和炎症与随着时间的推移肺功能增长减弱有关。结果 将为慢性肺部疾病进展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感染艾滋病毒的青少年中， 可以通过预防和治疗干预来减轻慢性肺病的负担。

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. Research proposed in this funded extension of her K23 Career Development Award builds on her previous and ongoing work, which demonstrates a substantial burden of chronic lung disease among adolescents living with HIV in a resource-limited setting. This extension will provide Dr. Attia with essential protected time to complete longitudinal analyses for Aim 2 and 3 of her K23 research, submit R01 applications, and continue training to support her goal of becoming an independent investigator at the intersection of pulmonary disease, HIV and global health. During the extension, Dr. Attia will continue to solidify her expertise in: 1) training in analysis of lung growth in adolescents; 2) advanced biostatistical methods to analyze complex correlated and missing data. These objectives will be achieved through a career development plan that incorporates coursework and continued mentoring by an advisory committee with expertise in lung disease and lung growth, HIV, epidemiology, biostatistics, and the use of biospecimens in clinical research. 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 achieve academic success. As co-director of the UW Department of Global Health Teaching, Research and Expert Education program, Dr. Attia will have full access to resources that support the administrative, clinical, laboratory and database management infrastructure for clinical research at the UW-affiliated Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. She will also have access to biostatistical support through the UW CTSA and School of Public Health. Research: During this extension, Dr. Attia will examine differences in subtypes, risk factors and mechanisms of chronic lung disease, based on repeat pre- and post-bronchodilator spirometry obtained over 3-4 years in 161 adolescents living with HIV from the Hope Center compared to 174 HIV-uninfected adolescents. She will: 1) determine the role of HIV on change in lung function over time, considering the complex interplay with other risk factors including malnutrition and indoor biofuel burning; 2) evaluate whether HIV severity, and biomarkers of immune activation and inflammation are associated with diminished lung function growth over time. Findings will provide novel insights into subtypes and pathophysiologic mechanisms of chronic lung disease progression in adolescents living with HIV 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.