Pharmacological and physiological response in Apoe−/− mice exposed to cigarette smoke or e-cigarette aerosols

Electronic cigarettes (e-cigs) are popular nicotine delivery devices, yet the health effects remain unclear. To determine equivalent biomarkers, we characterized the immediate response in Apoe-/- mice exposed to tank/box-mod e-cig (e-cigtank), pod e-cig (e-cigpod), or cig smoke.Reproducible puff profiles were generated for each aerosol and delivered to Apoe-/- mice via a nose-only exposure system. Serum cotinine levels were quantified at various time points through ELISA and utilized to model cotinine pharmacokinetics. In addition, particle size measurements and mouse respiratory function were characterized to calculate particle dosimetry.Cig and e-cigtank particles were lognormally distributed with similar count median diameters (cig: 178 ± 2, e-cigtank: 200 ± 34nm), while e-cigpod particles were bimodally distributed and smaller (116 ± 13 and 13.3 ± 0.4 nm). Minute volumes decreased with cig exposure (5.4 ± 2.7 mL/min) compared to baseline (90.8 ± 11.6 mL/min), and less so with e-cigtank (45.2 ± 9.2 mL/min) and e-cigpod exposures (58.6 ± 6.8 mL/min), due to periods of apnea in the cig exposed groups. Cotinine was absorbed and eliminated most rapidly in the e-cigpod group (tmax = 14.5; t1/2' = 51.9 min), whereas cotinine was absorbed (cig: 50.4, e-cigtank: 40.1 min) and eliminated (cig: 104.6, e-cigtank: 94.1 min) similarly in the cig and e-cigtank groups. For exposure times which equate the area under the cotinine-concentration curve, ∼6.4× (e-cigtank) and 4.6× (e-cigpod) more nicotine deposited in e-cig compared to cig exposed mice.This study provides a basis for incorporating cotinine pharmacokinetics into preclinical exposure studies, allowing for longitudinal studies of structural and functional changes due to exposure.This study highlights that pod e-cigs deliver smaller particles than tank/box-mode e-cigs and cig smoke. Minute volumes were substantially reduced in cig smoke-exposed mice, due to periods of apnea, whereas only expiration times increased in the e-cig-exposed groups. More particles deposit in e-cig exposed mice, compared to the cig group, for equivalent daily area under the cotinine concentration curve.