Multidimensional exposure architecture shapes vaping-associated transcriptomic dysregulation in oral epithelium

Area of Science:

• Molecular biology
• Transcriptomics
• Public health

Background:

• Electronic cigarette (e-cig) use, or vaping, is linked to gene and molecular pathway dysregulation in epithelial tissues.
• The specific impact of vaping dose and product characteristics on these transcriptomic changes remains unclear.

Purpose of the Study:

• To systematically evaluate the contributions of dose and product characteristics to vaping-associated transcriptomic alterations.
• To compare molecular changes induced by vaping versus traditional cigarette smoking.

Main Methods:

• RNA-sequencing of oral epithelial cells from e-cig users, smokers, and non-users.
• Differential gene expression analysis using limma-voom, controlling for covariates.
• Assessment of dose metrics (e-liquid, e-nicotine, years vaped, cotinine) and product features (device generation, flavor).

Main Results:

• Both vaping and smoking altered gene expression compared to non-users, with some overlapping differentially expressed genes (DEGs).
• Vaping-associated DEGs showed heterogeneous dose-response patterns, with device generation and flavor explaining additional variability.
• Smoking-associated DEGs demonstrated more consistent dose-dependent responses.

Conclusions:

• Vaping-induced transcriptomic dysregulation results from combined dose and product characteristic influences, differing structurally from smoking.
• Multidimensional exposure metrics and product features are crucial for understanding e-cig biological complexity and informing public health policy.