High-resistance coils in E-cigarettes increase heavy metals leaching into aerosols to cause oxidants generation in human bronchial epithelial cells at air-liquid interface: A unique non-animal methodological approach on vaping studies

Electronic cigarettes (e-cigs) use electrical resistance (sub-ohm to above-ohm) to heat coils that vaporize e-liquids for the generation of aerosols, which are inhaled directly. The effect of varying coil resistances on the production of toxicants in e-liquid aerosols remains unclear. In this study, we examined how varying coil resistance (0.6 Ω (sub-Ohm), 0.9 Ω (intermediate-Ohm), or 1.4 Ω (above-Ohm)) affects the physicochemical properties of e-cig aerosols, including mass median aerodynamic diameter (MMAD), size distribution, heavy metals, acellular reactive oxygen species (ROS), and volatile organic compounds (VOCs) in PG/VG, PG/VG with nicotine, and commercially available menthol and tobacco-flavored e-liquids. Further, we examined how varying coil resistance affected cytotoxicity and inflammatory mediator (interleukin-6) release by normal human bronchial epithelial cells (NHBE) that were exposed to e-cig aerosols at the air-liquid interface (ALI), a unique non-animal new methodological approach for vaping studies. Sub-ohm coils led to increased MMAD, while above-ohm coils produced finer particles and contained higher levels of aluminium, lead, chromium, and nickel, depending on the e-liquid formulation. Additionally, above-ohm coils significantly increased ROS generation in aerosols from commercially available flavored e-liquids, which in turn led to greater cellular ROS production in ALI-cultured NHBE. Both sub-ohm and above-ohm coils induced similar interleukin-6 release. Conversely, for cytotoxicity, PG/VG and menthol aerosols from sub- and intermediate-Ohm coils significantly raised LDH release. Overall, sub-ohm coils produce larger aerosols, above-ohm coils contain higher concentrations of heavy metals and ROS, whose toxicological impacts are reflected by the physiologically relevant in vitro lung models at the air-liquid interface.