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.

PROJECT NARRATIVE Despite increasing awareness of post-tuberculosis respiratory morbidity in adults, there is no data in children yet. An estimated 5-10 million children survived tuberculosis between 2000 and 2017 and are at potential risk of lung sequelae. An improved understanding of the impact of tuberculosis and respiratory virus infections on lung health in children could inform strategies to significantly improve the health of young children.