1. E-cigarettes (ECs) are projected to exceed combustible cigarette use within two years. Policy makers, health officials, and regulators are concerned that newer nicotine salt-based Ecs that use high concentrations of nicotine in their e-liquids are a major reason for this rapid growth in use. The US Food and Drug Administration (FDA) has regulatory authority to set appropriate tobacco product standards to protect public health and has shown interest in exploring a product standard limiting the level of nicotine in e-liquids. While this regulatory consideration has merit, emerging research suggests it may be misguided, leading to a product that is just as addictive but more harmful. Specifically, among users of earlier, freebase nicotine Ecs (i.e., cig-a-like, tank systems), use of low nicotine e-liquids was associated with a 9-fold increase in e-liquid consumption and all of its related toxicants, likely due to compensatory puffing. The consequences of consuming more e-liquid because of lower nicotine concentration remains an important knowledge gap. Moreover, the National Academies of Science, Engineering, and Medicine have concluded that completely substituting Ecs for cigarettes results in less short-term harm than continued smoking, but the impact of low versus high nicotine concentration e-liquids on a smokers' ability to completely switch to Ecs (versus become 'dual users' or continue smoking) is currently unknown. African American (AA) smokers, who take larger puffs, inhale more intensely, and extract more nicotine and harmful constituents per cigarette smoked, may be particularly impacted by nicotine product standards placed on EC - i.e., greater compensatory puffing and more e-liquid and related toxicant consumption at lower e-liquid concentrations. Unfortunately, the vast majority of information on Ecs and potential product standards come from white populations and have largely ignored African American (AA) smokers who bear a disproportionate burden of tobacco-related morbidity and mortality. As the FDA considers regulatory action to limit the level of nicotine in e-liquids to protect public health, it is critical that research considers vulnerable populations and does not widen disparities.

The long-term goal is to inform a tobacco landscape that will minimize tobacco-related harms and downstream health inequities. The overall objective of this application is to understand the impact of e-liquid nicotine concentration on compensatory puffing, EC and cigarette use patterns (exclusive EC, dual EC-cig, exclusive cig), and resultant exposure to biomarkers of harm among AA and white smokers. Adult AA and white smokers will complete two study phases. In Phase 1, using a randomized crossover design, participants will complete two standardized, 10-puff vaping bouts over 5 mins followed by a 60-minute ad libitum vaping session, using two e-liquids that differ only by nicotine concentration (5% vs. 1.8%) to examine the effect of nicotine concentration on in-lab compensatory puffing, nicotine exposure, and e-liquid consumption. In Phase 2, the same participants will be randomized to 5% or 1.8% nicotine e-liquid and instructed to switch completely for 6 weeks to examine the impact of nicotine concentration on short-term, real-world EC use patterns and related biomarkers of exposure (e.g., exhaled carbon monoxide, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), lung inflammatory markers). The central hypothesis is that, compared to the high nicotine concentration, while vaping the low nicotine concentration, users will engage in compensatory puffing, resulting in greater e-liquid consumption (Phase 1). Moreover, rates of dual use and continued smoking will be higher for the low (versus high) nicotine concentration and will result in greater exposure to toxicants (Phase 2).