Abstract Rationale The rapid rise in nicotine and cannabis vaping, along with dual use of vapes with combustible tobacco or cannabis, has raised concerns about their health effects. The biological effects of nicotine and cannabis vaping, particularly in the context of dual use with combustible products, remain poorly defined. Plasma-based metabolomic and proteomic profiling enables identification of systemic molecular alterations associated with inhalant exposure, with the goal of identifying new reactive biomarkers. This integrative approach provides new insight into the metabolic and inflammatory pathways affected by chronic vaping and smoking behaviors. Method A longitudinal study of human subjects ages 18-35 was conducted. Subjects were recruited and enrolled, underwent informed consent, and were categorized into inhalant groups based on self-report: non-vaper/non-smoker control, nicotine vaper, cannabis vaper, both nicotine and cannabis vaper (dual vaper), and vaping of nicotine or cannabis along with combustible smoking of tobacco and/or cannabis (dual vaper and smoker). Data was collected from 25 controls, 36 nicotine vapers, 2 cannabis vapers, 9 dual vapers, and 23 dual vapers and smokers. Plasma samples from 78 subjects underwent NULISAseq proteomic profiling as well as broad metabolomic analysis. Results Out of 250 proteins in the NULISAseq panel, 32 proteins were found to be significantly altered in nicotine vapers relative to non-vaping/non-smoking controls in a t-test after adjusting for multiple comparisons with Benjamin-Hochberg corrections. Overrepresentation analysis revealed activation of interleukin receptor steroid receptor coactivators (Src) homology and collagen homologous protein (SHC) signaling, tumor necrosis factor (TNF) binding to physiological receptors, and interleukin (IL)-2 family signaling. A total of 18594 metabolites were measured across all subjects. Further analysis comparing inhalant groups is pending. Conclusion Young healthy vapers of nicotine e-cigarettes had distinct alterations in their circulating proteins compared to non-vaping/non-smoking controls, suggesting broad, systemic effects of e-cigarette exposure. These proteomic changes indicate activation of multiple inflammatory pathways. IL-2 signaling was particularly affected, suggesting dysregulated cytokine-mediated immune signaling in nicotine vapers. These pathways will be further defined when coupled with the finished metabolomic analysis. Additionally, further studies with larger sample sizes may be needed to elucidate proteomic and metabolomic changes explicitly associated with cannabis vaping, dual vaping, and/or dual vaping and smoking. This abstract is funded by: NIH NHLBI, R01 HL137052 NIH NHLBI, K24 HL155884 TRDRP T30IP0965 TRDRP T34IR8251 VA Merit Award, 1I01BX006447
Kasaraneni et al. (Fri,) studied this question.