Impact of e-cigarette nicotine concentration on compensation, cigarette use, and biomarkers of exposure and harm among adults who smoke

Electronic cigarette (EC) use is projected to exceed cigarette smoking within two years. Nicotine salt-based ECs have raised concerns due to their high concentrations of nicotine, potentially contributing to their rapidly increasing popularity. The US Food and Drug Administration (FDA) has regulatory authority over ECs and has shown interest in exploring a product standard to limit the allowable level of nicotine in EC e-liquids. While the proposed product standard has merit, emerging research suggests that it could lead to a product that is just as addictive but more harmful. As more smokers switch to ECs, it is not known how they will use these products. No studies have investigated how rates of compensatory puffing when using ECs differ as a function of nicotine concentration among adults who smoke or how the nicotine concentration of e-liquids could influence their rates of compensation, substitution, and EC-related toxicant exposure. The proposed study will provide this scientific evidence to inform regulation and to maximize public health benefit and limit potential harm to users. Adults who smoke (N = 48) will complete two study phases. In Phase 1, participants will complete two standardized, 10-puff vaping bouts followed by a 60-minute ad libitum vaping session, using two e-liquids that differ only by nicotine concentration (5% vs. 1.8%). Phase 1 will provide objective data regarding rates of compensation as a function of nicotine concentration. In Phase 2, the same participants will be randomized to 5% or 1.8% nicotine e-liquid and instructed to switch to them completely for 6 weeks. The randomized trial will allow us to understand the comparative efficacy of 1.8% vs. 5% nicotine e-liquid on substitution rates and adverse health outcomes, including exposure to non-nicotine constituents, in the short-term under real-world use conditions. If reduced nicotine ECs were to result in greater e-liquid consumption via compensation, reduced substitution rates, and/or greater exposure to toxicants, then this would suggest that a nicotine product standard placing a limit on allowable levels of nicotine in e-liquid would lead to a product that is just as addictive but possibly more harmful. This innovative study will provide the scientific foundation needed to establish effective regulatory strategies for nicotine product standards that optimize public health. The project will serve as an incredibly valuable training experience and will establish the K01 candidate, Dr. Eleanor Leavens, as an independent tobacco regulatory scientist and launch Dr. Leavens’ career in substantial and measurable ways.