The long-term consequences of pulmonary tuberculosis and respiratory viruses on lung health in young South African children

项目摘要 候选人：货车德Zalm博士是高度积极性，以寻找创新的可行的解决方案，以改善长期 肺结核（TB）和其他疾病高负担环境中弱势儿童的肺部健康结果 呼吸道传染病她的总体职业发展目标是成为一名独立的临床医生 具有转化临床研究设计、实施和分析专业知识的科学家， 有效解决生活在低收入和中等收入国家的儿童的高度优先的肺部健康问题 （中低收入国家）。她的总体目标由三个具体的培训目标支持：1）设计和实施研究 重点关注儿童临床结核病研究中一个独特的、尚未解决的方面。其中包括一个在- 深入了解纵向数据分析和先进的生物统计学，需要分析这一丰富的， 具有长期结果的独特队列，2）发展成为儿科结核病的内容专家和思想领袖 和肺部健康评估，以及3）发展将关键研究结果转化为相关临床研究的技能 对政策和实践产生影响的准则。这种分析，临床和翻译技能的结合是 需要最大限度地发挥儿童转化临床研究的影响，特别是在中低收入国家， 传染病导致显著发病率，包括长期肺健康结果。货车德医生 Zalm拥有强大的机构支持，并组建了一支强大的美国和国际指导团队， 在儿科结核病和肺部健康研究的所有关键方面都有丰富的经验。 研究项目：尽管对成人结核病后呼吸道疾病发病率的认识不断提高， 孩子据估计，2000年至2017年间，有500万至1000万儿童在结核病中幸存，并处于潜在风险之中。 肺结核后遗症出生前和出生后早期是肺发育的最关键时期。 因此，由于这种慢性疾病，生命早期的PTB事件可能具有毁灭性的长期影响。 对幼儿肺部健康的影响。 我建议使用一项已建立的队列研究“Umoya”来调查结核病对肺部健康的影响， 提供了一个独特的机会来表征PTB和其他常见呼吸道疾病的长期影响， 病原体对肺结核儿童肺部健康的影响，以及良好的特征对照组。具体目标 1将调查长期呼吸系统发病率，并评估呼吸系统不良结局的风险因素， 调查儿童肺结核。具体目标2将描述南非儿童的肺功能轨迹 调查PTB。我提议的研究旨在定义和表征呼吸系统疾病的频谱， PTB幸存儿童的发病率。更好地了解结核病和其他疾病的影响 改变因素，如病毒合并感染，对儿童肺部发育的影响将为未来的战略提供信息， 预防呼吸道疾病在以后的生活。通过这项研究，我将获得相关的研究技能，建立 我自己作为一个独立的研究人员，并将使用这个独特的数据集申请未来的R 01赠款资金。

PROJECT SUMMARY Candidate: Dr. van der Zalm is highly motivated to find innovative feasible solutions to improve the long-term lung health outcomes in vulnerable children in settings with high burden of tuberculosis (TB) and other respiratory infectious diseases. Her overall career development goal is to become an independent clinician scientist with expertise in the design, implementation and analysis of translational clinical research, in order to effectively address high-priority lung health issues in children living in low- and middle- income countries (LMICs). Her overall goal is supported by three specific training aims: 1) designing and implementing research focused on a unique and as yet unaddressed aspect of clinical TB research in children. This includes an in- depth understanding of longitudinal data analysis and advanced biostatistics required to analyse this rich and unique cohort with long-term outcomes, 2) to develop into a contents expert and thought leader in pediatric TB and lung health assessment, and 3) to develop the skills to translate key research findings into relevant clinical guidelines to impact on policies and practice. This combination of analytical, clinical and translational skills is required to maximize the impact of translational clinical research in children, especially those in LMICs, where infectious disease contribute to significant morbidity including long-term lung health outcomes. Dr. van der Zalm has strong institutional support and has assembled a strong US and international mentoring team highly experienced in all critical aspects of pediatric TB and lung health research. Research project: Despite increasing awareness of post-TB respiratory morbidity in adults, there is no data in children. An estimated 5-10 million children had survived TB between 2000 and 2017 and are at potential risk of post-TB lung sequelae. The pre- and early postnatal years are the most critical period of lung development. Therefore, PTB events early in life due to this chronic disease, could have devastating long-term consequences on lung health of young children. I propose to investigate the impact of TB on lung health using an established cohort study, “Umoya,” which provides a unique opportunity to characterize the long-term effect of PTB and other common respiratory pathogens on lung health in children investigated for PTB, with well-characterized control groups. Specific aim 1 will investigate the long-term respiratory morbidity and evaluate risk factors for poor respiratory outcomes in children investigated for PTB. Specific aim 2 will describe lung function trajectories in South African children investigated for PTB. My proposed research aims to define and characterize the spectrum of respiratory morbidity in children who have survived PTB. An improved understanding of the impact of PTB and other modifying factors, e.g. viral co-infections, on lung development in children will inform future strategies to prevent respiratory illness later in life. Through this research I will obtain relevant research skills, establishing myself as an independent researcher and will use this unique dataset to apply for future R01 grant funding.