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JGM, Adolescent, Humans, Smokers, Electronic Nicotine Delivery Systems, Transcriptome, Cross-Sectional Studies, Sputum, Tobacco Products, Tobacco

JAX Source

Respir Res. 2023;24(1):134







(1) Scholars in Medicine – seed grant, Department of Medicine, University of Connecticut. (2) Seed grant Institute for Systems Genomics. (3) Clinical Research Center, University of Connecticut. (4) PRIDE – AIRE, NHLBI small project grant. (5) R01 CA207491 Minority Supplement. (6) NIH NHLBI K24 HL155884 (LCA). (7) NIH NIAID R01 AI141609.


RATIONALE: Electronic (e)-cigarettes are popular among youth and cigarette smokers attempting to quit. Studies to date have focused on the utility of e-cigarettes as a smoking cessation tool, but the biological effects are largely unknown.

OBJECTIVES: To identify transcriptomic differences in the blood and sputum of e-cigarette users compared to conventional cigarettes smokers and healthy controls and describe biological pathways affected by these tobacco products.

METHODS: Cross-sectional analysis of whole blood and sputum RNA-sequencing data from 8 smokers, 9 e-cigarette users (e-cigs) and 4 controls. Weighted gene co-network analysis (WGCNA) identified gene module associations. Ingenuity Pathway Analysis (IPA) identified canonical pathways associated with tobacco products.

MAIN RESULTS: In blood, a three-group comparison showed 16 differentially expressed genes (DEGs); pair-wise comparison showed 7 DEGs between e-cigs and controls, 35 DEGs between smokers and controls, and 13 DEGs between smokers and e-cigs. In sputum, 438 DEGs were in the three-group comparison. In pair-wise comparisons, there were 2 DEGs between e-cigs and controls, 270 DEGs between smokers and controls, and 468 DEGs between smokers and e-cigs. Only 2 genes in the smokers vs. control comparison overlapped between blood and sputum. Most gene modules identified through WGCNA associated with tobacco product exposures also were associated with cotinine and exhaled CO levels. IPA showed more canonical pathways altered by conventional cigarette smoking than by e-cigarette use.

CONCLUSION: Cigarette smoking and e-cigarette use led to transcriptomic changes in both blood and sputum. However, conventional cigarettes induced much stronger transcriptomic responses in both compartments.


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