PROJECT SUMMARY This application is designed to provide me with the mentoring experience, training and access to resources from expert modeling groups that will allow me to achieve my long-term career goal to become an independent investigator with expertise in conducting population simulation modeling science for tobacco regulatory policy based on a systems thinking approach. My planned training and research activities will be guided by my mentors, Drs. David T Levy and Rafael Meza, well-known experts in the area of tobacco simulation modeling and regulatory science, and a team of expert collaborators and are intended to: increase my knowledge about the pathophysiology of pulmonary diseases, epidemiology and association between tobacco and respiratory diseases (i.e. Chronic Obstructive Pulmonary Disease COPD); acquire technical skills for the development and implementation of simulation modeling for impact analysis of tobacco regulatory policies; and develop specialized knowledge in the translation of tobacco simulation modeling results to inform policies. The objective of this research project is to build a COPD natural history model based on individual smoking (cigarette use) histories, that will be used to predict the long-term population impact of two FDA tobacco regulatory actions on COPD disease burden. COPD is one of the principal causes of morbidity and mortality in the US. The majority of the COPD cases could be prevented by reducing cigarette use. However, it is not yet clear the long-term impact of emergent regulations on recent cigarette use behaviors and chronic respiratory diseases like COPD. Understanding the long-term health respiratory effects of tobacco products is one of the FDA-Center for Tobacco Products' (CTP) highest priority. This study will produce evidence, using a public health standard, about the impact of cigarette-oriented control policies on COPD trends to inform FDA tobacco regulations. The project has three aims. Aim 1: Determining the impact of longitudinal changes in smoking behavior on lung function and COPD mortality: a Markov Model Analysis. Using data from the COPDGene cohort, I will assess how changes in smoking behaviors impact the lung function decline and mortality of tobacco associated COPD. Aim 2 Develop a COPD Natural History microsimulation model (COPD-NHM) to estimate the future COPD incidence, prevalence and COPD associated respiratory and lung cancer deaths dependent on individual smoking histories (baseline scenario). Aim 3. Predict potential US future trends in COPD under two FDA tobacco regulatory scenarios. The validated COPD-NHM will be used to estimate the population impact of 1. cigarette pack graphic health warnings and 2. menthol cigarettes ban on COPD morbidity and mortality. The proposed research will lead to the submission of an R01 award to expand the COPD-NHM to include other non-cigarette products, and other relevant behavioral, sociodemographic and biological characteristics to encompass the various ways in which novel tobacco or ENDS regulatory policies could impact COPD and COPD associated cancer progression.