Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model

Area of Science:

• Pulmonary Medicine
• Toxicology
• Immunology

Background:

• Electronic nicotine delivery systems (ENDS) use is widespread, raising public health concerns, particularly after the 2019 EVALI outbreak.
• Research on the chronic pulmonary effects of ENDS delivery vehicles (vegetable glycerin and propylene glycol) is limited.
• Vitamin E acetate has been linked to EVALI, but the impact of base e-liquid components requires further investigation.

Purpose of the Study:

• To investigate the effects of inhaling common electronic-cigarette (e-cig) aerosol constituents, vegetable glycerin (VG) and propylene glycol (PG), on lung function and immune responses.
• To determine if VG/PG aerosols, with or without flavoring, induce lung inflammation and alter pulmonary physiology.
• To assess the impact of VG/PG aerosol exposure on immune cell populations and bioactive lipid mediators in the lungs.

Main Methods:

• Adult female mice were exposed to filtered air, 70%/30% VG/PG aerosol, or 70%/30% VG/PG with vanilla flavoring for 6 weeks.
• Lung function was assessed before sacrifice.
• Broncho-alveolar lavage fluid and lung tissue were analyzed for immune cell profiles, lipid mediators, gene expression, and histopathology.

Main Results:

• Exposure to VG/PG aerosols, with or without vanilla flavoring, increased lung tidal and minute volumes and tissue damping.
• Immunophenotyping revealed increased dendritic cells, CD4+ T cells, and CD19+ B cells in VG/PG exposed mice compared to controls.
• Bioactive lipid analysis showed increased levels of the anti-inflammatory mediator 2-AG and the inflammatory mediator 12-HETE, indicating altered immunoregulatory pathways.

Conclusions:

• The primary constituents of e-liquids, vegetable glycerin (VG) and propylene glycol (PG), are not inert when aerosolized and inhaled.
• VG/PG aerosols disrupt lung immune homeostasis by altering immune cell populations and bioactive lipid mediator levels.
• These findings demonstrate that e-cig delivery vehicles can negatively impact lung health, contributing to inflammation and altered physiological function.