Urinary tobacco and nicotine exposure biomarkers as predictors of transitions between cigarette and e-cigarette use in the Exhale longitudinal cohort study

Abstract Introduction Urinary tobacco and nicotine exposure biomarkers may be predictive of subsequent transitions in product use. Methods We used data from an observational study of 371 adults who smoked cigarettes daily, some of whom also used e-cigarettes, and who were followed every two months for up to two years (Wisconsin, US, 2015–19). Using a multistate transition model, we assessed continuous associations between transition propensities and urinary tobacco biomarker concentrations, namely 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL) and NE-2 (cotinine + trans-3'-hydroxycotinine), the nicotine metabolite ratio (NMR; trans-3'-hydroxycotinine:cotinine), and NNAL:NE-2, measured every 4 months. Results The biomarkers were generally more predictive of transitions from dual use, but not from cigarette-only use, than self-reported product use was. Propensity to stop smoking cigarettes decreased with increasing concentrations of NNAL and NE-2, for both participants who smoked only cigarettes and those who used both cigarettes and e-cigarettes. For example, we estimated that, at 20 pg NNAL per mg creatinine, 30.2% (95%CI, 14.6%, 47.0%) of those who only smoke cigarettes and 26.6% (95% CI, 11.3%, 42.5%) who dual use would transition to non-current cigarette use and e-cigarette use in one year, while at the 200 pg/ng, we estimate these probabilities to be 3.2% (95%CI, 1.7%, 5.8%) and 3.9% (95% CI, 1.9%, 8.5%), respectively. The ratio NNAL:NE-2 was predictive of transitions from dual use to cigarette-only (higher ratio) or e-cigarette-only (lower ratio) use. Conclusions Urinary tobacco biomarkers were non-linearly associated with transitions in tobacco product use and may guide the development of clinical interventions to promote harm-reducing product use transitions.