Pulmonary effects of inhaled e-cigarette aerosol in mouse models of pregnancy, asthma, and EVALI
Creators: name: Ng, Vingie
Publisher: name: University of Iowa
Year: 2024
Subjects: e-cigarette
ENDS
EVALI
JUUL
menthol
vaping
Public Health

description: Electronic cigarettes (e-cigarettes) are nicotine delivery devices that became popular with youth who never smoked. This eventually grew into a “youth vaping epidemic.” When this precipitated a public health crisis in 2019 as cases of “e-cigarette or vaping product use associated lung injury” (EVALI) befell the U.S., it highlighted how little was known about these products. Our overall goal was to investigate a popular brand of e-cigarette (JUUL) for its potential to contribute to pulmonary inflammation. We used mouse models that translate into young never-smokers, pregnant women, asthmatic individuals, and EVALI patients. The experiments herein used a nose-only inhalation system to minimize non-inhalational routes of exposure. For the two flavors we tested in these studies, high concentrations (&gt;100 million/cm3 ) of both fine and ultrafine particles were measured in the aerosols, with Virginia Tobacco and Menthol particles having similar aerodynamic diameters of 108 (2.1) nm and 113 (2.2) nm, respectively. This is a concern because these small particles penetrate deeper into the lungs.
description: Overall, both subacute and subchronic exposures to 5% nicotine strength Virginia Tobacco and Menthol flavors did not yield significant findings of overt lung inflammation nor cytotoxicity nor impaired lung function. However, in the subacute exposure with male mice, both flavors significantly increased glutathione disulfide while only Menthol significantly increased total reduced glutathione in lung tissue, altogether suggesting alterations in redox homeostasis.
description: In the preconception/prenatal exposure (pregnancy model), there was no increased lung inflammation, but liver and placenta data suggested altered lipid and estrogen metabolism and signaling. Compared to pregnant sham-exposed mice, liver expression of Fasn, Scd1, Sts, Esr1, and Cyp2a5 were upregulated in Virginia Tobacco-exposed pregnant mice. Fasn was also upregulated in placentas, but more so in Menthol-exposed mice. Reproductive fitness and fetal vi outcomes were suboptimal in Virginia Tobacco-exposed mice, in comparison to sham and Menthol groups. Altogether, the flavors exerted differential effects, and the impact of pregnancy made these effects more pronounced for some endpoints.
description: In the asthma model combined with Menthol exposure, airway inflammation and airway hyperreactivity (AHR) were differentially impacted according to sex. Whereas the male asthma model exhibited increased cellular infiltration in the lungs and trended towards mucus hypersecretion with the addition of vaping, females did not. However, the female asthma model with vaping displayed an increase in baseline respiratory resistance and altered AHR, whereas males did not. Neither Th2 cytokines nor total IgE (both measures of asthma severity) significantly increased with the addition of vaping. Together, these data suggest alterations in airway inflammation, mucus hypersecretion, and AHR in response to subacute exposure to Menthol, which could potentially exacerbate asthma symptoms in a sex-specific manner.
description: In the EVALI model, inhaled aerosolized vitamin E acetate (VEA) induced clinical features consistent with EVALI, such as profound lung inflammation and impaired lung function. In the lungs, VEA exposure significantly increased pro-inflammatory cytokines and cytotoxicity and worsened AHR. Findings were consistent across inbred and outbred mouse strains and correspond to symptoms seen in patients (i.e., lipid-laden macrophages). We also found a systemic increase of 4-HNE, a marker of lipid peroxidation. Altogether, this provides additional evidence to support VEA as a culprit in the EVALI crisis.
description: The exposure studies undertaken herein used mouse models to address gaps about pregnancy, asthma, and EVALI. Although the public health potential for e-cigarettes has yet to be established, the health ramifications for young never-smokers have become clearer, but more independent research on e-cigarette toxicity is still needed to fill the current knowledge gaps.