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

项目总结 候选人：范德扎尔姆博士非常积极地寻找创新的可行解决方案来改善长期 结核病和其他疾病高负担环境中易受感染儿童的肺部健康结果 呼吸道传染病。她的整个职业发展目标是成为一名独立的临床医生 在翻译临床研究的设计、实施和分析方面具有专业知识的科学家，以便 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 (LMIC)。她的总体目标得到了三个具体培训目标的支持：1)设计和实施研究 重点关注儿童结核病临床研究的一个独特且尚未解决的方面。这包括一个In- 深入了解纵向数据分析和高级生物统计学，以分析这一丰富和 具有长期效果的独特队列，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)培养将关键研究成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型临床研究的影响，特别是在LMICs中， 传染病导致了重大的发病率，包括长期的肺部健康后果。范德博士 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 在儿科结核病和肺健康研究的所有关键方面都有经验。 研究项目：尽管人们对成人结核病后呼吸道发病率的认识不断提高，但没有 孩子们。据估计，在2000至2017年间，有500-1000万儿童在结核病中存活下来，处于潜在的危险之中 结核病后的肺部后遗症。出生前和出生后早期是肺发育最关键的时期。 因此，由于这种慢性疾病，肺结核在生命早期发生的事件，可能会产生破坏性的长期后果 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，该研究 提供了一个独特的机会来描述肺结核和其他常见呼吸道疾病的长期影响 研究肺结核病原体对儿童肺部健康的影响，并设特征明确的对照组。特定目标 1将调查长期呼吸道发病率和评估不良呼吸结局的危险因素。 儿童接受肺结核调查。《特定目标2》将描述南非儿童的肺功能轨迹 已就肺结核进行调查。我提出的研究旨在定义和描述呼吸系统的光谱 肺结核存活者的发病率。更好地了解结核病和其他疾病的影响 改善儿童肺部发育的因素，例如病毒合并感染，将为未来的战略提供信息 在以后的生活中预防呼吸道疾病。通过这次研究，我将获得相关的研究技能，建立 作为一名独立研究人员，我将使用这一独特的数据集来申请未来的R01拨款。

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.