Measured and modelled nicotine emissions predict systemic nicotine exposure across sub-ohm and pod-based ENDS

BACKGROUND: Electronic nicotine delivery systems (ENDS) can deliver nicotine at levels that rival or exceed cigarettes, shaping both smoking cessation outcomes and the emergence of nicotine dependence in previously nicotine-naïve users. We evaluated whether systemic nicotine exposure is associated with emitted nicotine dose measured in the laboratory and estimated from ENDS device physics. METHODS: Across two clinical studies, we compared plasma nicotine boost following ad libitum ENDS puffing sessions with nicotine doses derived by two complementary approaches: (1) analysis of nicotine content in puffing-machine-generated aerosols and (2) physics-based computer simulations. RESULTS: Across both clinical datasets and three device types, plasma nicotine boost was associated with emitted nicotine dose measured in the laboratory (~40% of variance explained) and with that predicted by a first-principles model of coil heating and liquid vaporisation (~33%), despite not incorporating individual-participant physiological differences. CONCLUSIONS: These results support a mechanistic link between ENDS device parameters and systemic nicotine exposure. Physics-based models may support prospective population-level evaluation of nicotine delivery, including for hypothetical products, for which emissions data are not yet available.