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-cig_tank), pod e-cig (e-cig_pod), 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-cig_tank particles were lognormally distributed with similar count median diameters (cig: 178 ± 2, e-cig_tank: 200 ± 34nm), while e-cig_pod 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-cig_tank (45.2 ± 9.2 mL/min) and e-cig_pod 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-cig_pod group ($$ = 14.5; $$ = 51.9 min), whereas cotinine was absorbed (cig: 50.4, e-cig_tank: 40.1 min) and eliminated (cig: 104.6, e-cig_tank: 94.1 min) similarly in the cig and e-cig_tank groups. For exposure times which equate the area under the cotinine-concentration curve, ∼6.4× (e-cig_tank) and 4.6× (e-cig_pod) 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.