Sex-specific alterations in pulmonary metabolic, xenobiotic and lipid signalling pathways after e-cigarette aerosol exposure during adolescence in mice

Background E-cigarette use is now prevalent among adolescents and young adults, raising concerns over potential adverse long-term health effects. Although it is hypothesised that e-cigarettes promote inflammation, studies have yielded conflicting evidence. Our previous work showed that JUUL, a popular e-cigarette brand, elicited minimal lung inflammation but induced significant molecular changes in adult C57BL/6 mice. Methods Now, we have profiled immunological and proteomic changes in the lungs of adolescent male and female BALB/c and C57BL/6 mice exposed to a flavoured JUUL aerosol containing 18 mg/mL of nicotine for 14 consecutive days. We evaluated changes in the immune composition by flow cytometry, gene expression levels by reverse transcription-quantitative PCR and assessed the proteomic profile of the lungs and bronchoalveolar lavage (BAL) by tandem mass tag-labelled mass spectroscopy. Results While there were few significant changes in the immune composition of the lungs, proteomic analysis revealed that JUUL exposure caused significant sex-dependent and strain-dependent differences in lung and BAL proteins that are implicated in metabolic pathways, including those related to lipids and atherosclerosis, as well as pathways related to immune function and response to xenobiotics. Notably, these changes were more pronounced in male mice. Conclusions These findings raise the possibility that vaping dysregulates numerous biological responses in lungs that may affect disease risk, disproportionally impacting males and raising significant concerns for the future health of male youth who currently vape. Data are available in a public, open access repository. Data are available on reasonable request. Proteomics data supporting the conclusions of this paper can be found at DOI: 10.6084/m9.figshare.26351740.