Available online 2 December 2023, 111052

Author links open overlay panel, , , , , , , , , , , , ABSTRACTBackground

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 users of 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 users completed five visits that differed by nicotine form (freebase or protonated) and nicotine flux (14 or 35 µg/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 µg/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.

Section snippetsINTRODUCTION

ENDS use in the U.S. has increased rapidly in the last decade, including among youth.(Dai and Leventhal, 2019) According to the National Youth Tobacco Survey (NYTS), approximately 2.5 million U.S. adolescents used ENDS in 2022. The widespread adoption by ENDS manufacturers of protonated (salt) nicotine liquids (Duell et al., 2019) has been associated with the rapid increase in the number of young ENDS users.(Glantz et al., 2022; Pierce et al., 2022) Nicotine salt products are found to be more

Participants and recruitment

This study was approved by the Institutional Review Board at the American University of Beirut (AUB). Written, informed consent was obtained from each participant and all participants were financially compensated for their time. Participants were recruited via flyers distributed at AUB and through social media channels. Eligible participants were healthy, above 18 years of age, and dual users of ENDS and combustible cigarettes. Smoking status was confirmed via an initial screening

RESULTS

Thirty-two participants were enrolled in this study. Participants had a mean age of 24(SD=6) years, ranging from 18-42 years. Of these, 23(72%) were male and 9(28%) were female. All participants met the CO threshold confirming smoking abstinence. The average CO level at baseline was 3 ppm (SD=2 ppm). Fifteen participants (47%) reported their usual nicotine strength, and none reported their nicotine form. The average history of use of any tobacco product among the participants was 6.2(SD=6)

DISCUSSION

In this study we sought to test how ENDS nicotine form and flux influence puffing behavior and mouth-level exposure to nicotine. Experienced ENDS users were recruited for five clinical laboratory visits which differed by nicotine flux and nicotine form. Each visit involved a 10-puff directed bout followed by 1-hour ad lib use. We measured puffing topography, ENDS liquid consumed, and mouth-level nicotine exposure for each use session. We found that nicotine form and flux strongly influenced

CONCLUSION

We found that ENDS with protonated nicotine elicit longer puffs and greater mouth-level exposure to nicotine. We also found that greater nicotine flux resulted in shorter puffs in both directed and ad lib bouts, fewer puffs in the ad lib bouts, and greater mouth-level nicotine exposure in the directed bouts only. This work highlights the importance of taking into consideration interactions between nicotine form and flux when considering nicotine regulation for ENDS. Research is needed on how

Role of Funding Source

Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Numbers R01DA052565 and U54DA036105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Uncited reference

(Allain et al., (2015))

CRediT authorship contribution statement

Conception: Soha Talih, Ahmad El-Hellani, Farid Talih, Stephen Baldassari, Martine Elbejjani, Thomas Eissenberg, Alan Shihadeh. Data Acquisition: Eliana Hanna, Rola Salman, Sally Salam, Rachel El-Hage, Nareg Karaoghlanian. Data Analysis: Soha Talih, Martine Elbejjani, Alan Shihadeh. Drafting, Critical Revision, and Final Approval: Soha Talih, Eliana Hanna, Sally Salam, Rola Salman, Rachel El-Hage, Nareg Karaoghlanian, Martine Elbejjani, Farid Talih, Najat Saliba, Stephen Baldassari, Ahmad

CRediT authorship contribution statement

Karaoghlanian Nareg: Methodology, Resources, Software, Supervision, Writing – review & editing. Talih Farid: Conceptualization, Investigation, Methodology, Writing – review & editing. Baldassari Stephen: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Writing – review & editing. Saliba Najat: Investigation, Methodology, Resources, Writing – review & editing. Elbejjani Martine: Data curation, Formal analysis, Investigation, Methodology, Validation, Writing –

Declaration of Competing Interest

The authors declare the following competing financial interest: Drs. Shihadeh and Eissenberg are paid consultants in litigation against the tobacco industry and the ENDS industry and are named on one patent for a device that measures the puffing behavior of ENDS users and on a patent application for a smoking cessation intervention. Dr. Eissenberg is also named on another patent application for a smartphone app that determines ENDS device and liquid characteristics.

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