Project Details

Defining the Role of Polymorphonuclear Neutrophils in Post-Tuberculosis Lung Disease in Children

Ye jin Kang, MD, MSc, MPP

Summary

BACKGROUND: Nearly two-thirds of pulmonary TB patients have respiratory sequelae after standard four drug anti-TB treatment. Mechanisms driving post-TB lung disease pathology are unknown; however, I hypothesized that polymorphonuclear neutrophils (PMNs) also known as neutrophils, which induce TB pathology and contribute to airway injury in other pulmonary disease, play a central role in driving post-TB lung disease in children. GAP: The majority of pediatric TB patients have post-TB lung disease, but little is known about the drivers of inflammation leading to long-term TB pulmonary outcomes. HYPOTHESIS: There will be increased prevalence of obstructive lung disease, primarily due to bronchiectasis, with increased cough frequency. Elevated neutrophil biomarkers at time of TB diagnosis will be associated with greater post-TB obstructive lung impairment through inflammation in the airways. METHODS: Through a prospective study leveraging banked sample in addition to newly enrolled patients through a collaboration with the Baylor College of Medicine TB Center for Clinical Excellence in Eswatini and UT Southwestern Medical Center, we will investigate how the acute inflammatory neutrophilic reaction in TB disease relates to lung function after TB treatment completion. We will comprehensively profile lung function by spirometry, symptom scoring, and x-ray imaging. RESULTS: Pending. IMPACT: The project may identify biomarker targets as well as develop mechanistic insight for future trials of host-directed therapy to improve long-term lung function outcomes in children with TB. No host-directed therapy currently exists and defining these pathological mechanisms may offer insight into therapeutic pathways that mitigate disease pathology and lead to lifelong benefits for children.