Influence of nicotine form and nicotine flux on puffing behavior and mouth-level exposure to nicotine from electronic nicotine delivery systems

Background: Nicotine form (freebase/protonated) and nicotine flux (rate at which nicotine is emitted) are two factors that can affect the dose of nicotine inhaled by individuals using electronic nicotine delivery systems (ENDS) because they can influence puffing behavior. The nicotine dose for each puff also is directly proportional to nicotine flux (i.e., dose/puff=nicotine flux*puff duration). This study examines the effect of nicotine form and flux on puffing parameters and mouth-level nicotine exposure. Methods: Thirty-two dual ENDS and combustible cigarette participants completed five visits that differed by nicotine form (freebase or protonated) and nicotine flux (14 or 35 mu g/sec); a zero-nicotine condition was a negative control. Participants used a Subox Mini C ENDS, powered at 20 W, during a 10-puff directed bout (B1) followed by a one-hour ad libitum bout (B2). Puffing parameters and mouth-level nicotine exposure were assessed using the American University of Beirut REALTIME instrument. Results: Relative to protonated nicotine, freebase nicotine was associated with lower total puff duration (puff duration*number of puffs), lower flow rate in B1, lower liquid consumption, and lower mouth-level nicotine exposure. Increasing nicotine flux from 14 to 35 mu g/sec was associated with lower total puff duration in both bouts, as well as lower liquid consumption. Increasing nicotine flux was associated with higher mouth-level nicotine exposure in B1 only. Conclusion: ENDS with protonated nicotine may enhance nicotine exposure by promoting longer puffing and thus greater dose delivered. This work highlights the importance of accounting for interactions between nicotine form and flux when considering nicotine regulation for ENDS.