PROJECT SUMMARY/ABSTRACT This is an application for the K23 Mentored Patient-Oriented Research Career Scientist Award for Trishul Siddharthan M.D. Dr. Siddharthan has shown great promise as a young investigator, and has experience conducting research in epidemiology and chronic disease in low- and middle-income countries (LMICs). However, he is now proposing to gain advanced training in conducting longitudinal analysis and randomized controlled trials requires additional training and mentorship to do so. His overall career goal is to become an independent investigator and expert in evaluating the effectiveness medical therapies for chronic respiratory diseases, and this award will provide Dr. Siddharthan with the support and training to accomplish this goal. He has assembled an experienced mentorship team including: Dr. William Checkley (Primary Mentor, Chronic Respiratory Diseases), Associate Professor (JHU); Dr. Robert Wise (Clinical Trials), Professor (JHU); Dr. James Tonascia (Biostatistics), Professor (JHU); and Dr. David Dowdy (Cost-evaluation), Associate Professor (JHU). Through a combination of close mentorship, formal coursework, and practical experience, Dr. Siddharthan proposes to accomplish the following training goals: 1) Advanced training in longitudinal analysis; 2) Advanced training in randomized controlled trials; and 3) Advanced training in cost-evaluation. Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, and over 90% of COPD-related deaths occurring in low- and middle-income countries (LMICs). Household air pollution (HAP) – from burning solid fuels such as wood, dung, agricultural crop waste, and coal for energy – is the primary risk factor for COPD in these settings. Biomass-related COPD has a distinct histopathology, phenotype and inflammatory profile when compared to tobacco mediated COPD. Despite the high global burden of biomass- related disease, little is known about the effectiveness of pharmacotherapies for biomass-related COPD; to date, no clinical trials have focused specifically on treatment of biomass-related COPD. Dr. Siddharthan proposes to assess the health impact of biomass-related COPD and test the effectiveness of low dose theophylline compared to standard therapy among adults with biomass-related COPD in Peru. He proposes to assess whether low-dose theophylline improves respiratory symptoms, decreases the inflammatory profile of serum biomarkers and whether administration attenuates the effect of HAP on lung function. He additionally aims to assess whether low-dose theophylline is a cost-effective intervention based on the incremental cost- effectiveness ratio and a range of willingness to pay thresholds. Results from this study will generate preliminary data to compete for an R01-level award to conduct an implementation-effectiveness hybrid trial in multiple communities to assess the impact of chronic pharmacotherapy for biomass-related COPD.