Understanding tobacco flavor effects on waterpipe smokers' experiences and exposuresAbstract:Waterpipe (WP) tobacco smoking (a.k.a. hookah, shisha, narghile) is increasing rapidly in theUnited States (US), particularly among young people. Time trends of WP smoking among youthin the US, show that WP smoking has become comparable to cigarette smoking among high-school students for the first time ever in 2014. Evidence suggests that WP smoking can lead todependence, other tobacco use, and many of the known smoking-related diseases includingcancer, cardiovascular disease and adverse pregnancy outcomes. These alarming trends led theFood and Drug Administration (FDA) in 2014 to propose including the WP under its regulatoryauthority, allowing the FDA to apply evidence-based regulatory approaches to control WP spreadin the US. Given the salience of flavored tobacco in shaping the “WP experience”, regulating WPtobacco flavor represents a promising approach for the FDA to curb WP use among US youth.This project aims to assist the FDA in these efforts by providing answers to specific questionspertinent to the potential of WP regulation through flavor. These include: - How would flavormanipulation affect the smoking experience and satisfaction of WP users at different stages oftheir smoking trajectory - How would smoking non-preferred flavor or unflavored WP tobaccoreflects on smokers' exposure to nicotine, and dependence; and - How would flavor manipulationinfluence puffing behavior and exposure to toxicants such as carbon monoxide (CO) among WPsmokers. Answers to these questions will help the FDA predict the impact of flavor regulation onWP experimentation and continued use. In this study, we will use clinical laboratory methods toanswer these questions, where we will recruit two groups of WP smokers based on their usefrequency: low (Beginners) vs. high frequency (Experienced) smokers (72/group; total 144; age18-30). Each participant will undergo 3 WP smoking sessions that differ by flavor (preferred flavor;non-preferred flavor; unflavored), while measurement of WP satisfaction, dependence, harmperception, and exposure to nicotine and toxicants will be conducted. The response of WPsmokers at different stages of their WP smoking trajectory (Beginners vs. Experienced) to flavormanipulation, will allow us to predict the effect of limiting flavors on a wide range of WP smokers.This project promises to provide the first evidence to guide the FDA in terms of the potential ofregulating WP flavored tobacco on WP uptake and use in the US.