Host- and pathogen-specific risk factors for post-tuberculosis lung disease among people successfully treated for TB in Lima, Peru: Beat-PTLD

Project Summary An estimated 10 million individuals develop TB disease each year, most of whom live in low-and middle- income countries. In addition to the morbidity and mortality associated with the disease episode itself, TB leads to long-term compromise of lung function and chronic respiratory disability even after successful TB treatment. Although preventive therapy and early TB diagnosis and treatment likely reduce this risk, many tuberculosis patients experience residual lung pathology, with studies demonstrating substantial pulmonary impairment due to obstructive lung disease, restriction, bronchiectasis, and pulmonary hypertension, as well as secondary non-tuberculosis lung infections including aspergillosis. A modeling exercise estimated that among the 122 million disability adjusted life years (DALYs) lost due to TB in 2019, 55 million (47%) resulted from post-TB lung disease (PTLD). Despite the enormous global burden of lung impairment following successful TB treatment, major knowledge gaps in PTLD hinder the identification of high-risk individuals and the development and testing of interventions to mitigate TB's long-term impact on lung function and overall health. These include lack of knowledge of the frequency of PTLD and its subtypes, of the risk factors for PTLD, and of the most efficient ways to screen for the disease. Here we propose to leverage an existing NIH-funded cohort study to evaluate 1000 successfully treated TB patients 2-3 years after their initial TB diagnosis —and 291 community controls—in Lima, Peru for the occurrence of lung impairment. We will use spirometry, high resolution chest CT, and echocardiography to characterize PTLD phenotypes in this cohort. We will estimate the relative risks of putative determinants of PTLD that were measured at the time of TB diagnosis and develop a predictive model that could be used to triage TB patients at high risk for PTLD for interventions. We will also assess the contributions of host and bacterial genetic variation in the etiology of the disease. Finally, we will assess the performance of a battery of functional assays, questionnaires, and biomarkers as screening tests for PTLD. The successful completion of this study will allow us to estimate the frequency of different types of PTLD among TB survivors, describe the host and bacterial factors that lead to PTLD, and identify the tools that enable accurate assessment of the extent of lung impairment.