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.