119 - The impact of nicotine metabolism on e-cigarette use and nicotine dependence in hospitalized youth

Publication Number: 119.6870

Stephani Stancil, Children's Mercy Hospitals and Clinics, Kansas City, MO, United States; Delwyn Catley, San Diego State University, San Diego, CA, United States; Nikki Nollen, University of Kansas School of Medicine, Kansas City, KS, United States; Erin C. Boone, Children's Mercy Hospital, Kansas City, MO, United States; Wendy Y. Wang, Children's Mercy Hospitals and Clinics, Kansas City, MO, United States; John Tumberger, Children's Mercy Hospitals and Clinics, Kansas City, MO, United States; Anna E. Burns, Children's Mercy Hospitals and Clinics, Leawood, KS, United States; Mariah Brewe, Children's Mercy Hospitals and Clinics, Kansas City, MO, United States; Hung-Wen Yeh, Children's Mercy Hospitals and Clinics, Kansas City, MO, United States; Abbey Masonbrink, Children's Hospital Los Angeles, Los Angeles, CA, United States

Background: E-cigarette use has risen drastically among youth and is linked with substance use disorders and worsened mental health outcomes. Varied nicotine metabolism in adults is linked to cessation success. Despite high rates of e-cigarette use, research on personalized nicotine dependence treatment in youth is lacking.

Objective: Our study objective is to evaluate the impact of variation in nicotine metabolism on e-cigarette use and nicotine dependence among hospitalized youth.

Design/Methods: Cross-sectional study of hospitalized youth aged 14-21 years with current e-cigarette use. Confidential self-report data included demographics, e-cigarette use (occasional [1-5 days], intermittent [6-19 days], frequent [≥20 days in the past month]), nicotine dependence [not, low, medium, high]). DNA was extracted for CYP2A6 Sanger sequencing. Nicotine, cotinine, and trans-3-hydroxycotinine were quantified in saliva using validated UPLC-MS/MS method and nicotine metabolism ratio (NMR) calculated (slow [1st quartile], normal [2nd-4th quartile]). CYP2A6 genotype-phenotype was grouped by activity score (AS) using functional data available in PharmVar (slow [AS < 1.25], normal [AS≥1.5]). Bivariate associations were evaluated by Fisher’s exact and Wilcoxon rank-sum tests.

Results: Among a diverse sample (n=106, Table 1) with a mean age 161.3 years, 40 (38%) reported frequent e-cigarette use and nicotine dependence scored high in 28% and medium in 22%. E-cigarette use varied by nicotine dependence categories (p < 0.001). CYP2A6 genotype-predicted phenotype was associated with NMR (p < 0.001), but not e-cigarette use (p=0.55) or nicotine dependence (p=0.82; Table 2). NMR phenotype (slow vs. normal) showed a significant association with nicotine dependence, but not with e-cigarette use (p=0.36; Table 3). More occasional (51%) and no/low dependent users (63%) had undetectable NMR.

Conclusion(s): In hospitalized youth with e-cigarette use, more than 1/3 reported frequent use and half were medium to highly nicotine dependent. CYP2A6 genotype was associated with altered nicotine metabolism, which was associated with nicotine dependence, such that slow metabolizers were less nicotine dependent.
Associations with e-cigarette use were limited by undetectable NMR in occasional users. National guidelines recommend nicotine replacement therapy for medium to highly nicotine dependent youth yet these are largely based on expert opinion rather than evidence. Critical future work includes fully powered trials to evaluate precision treatment for youth with nicotine dependence based on individual factors that influence nicotine metabolism.

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