Lung mitochondrial DNa copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers.

Introduction:
This text provides an analysis of a study examining the relationship between tobacco use and mitochondrial DNa (mtDNa) copy number (mtCN) in the lungs of young adults. The study compares mtCN in smokers, never-smokers, and electronic cigarette (EC) users, and explores the association of mtCN with nuclear biomarkers, including immune responses, genome-wide DNa methylation, and gene expression. The study also compares EC-specific mtCN associated signatures with respiratory diseases.

Key Points:

* The study found that smoking was associated with increased mtCN in the lungs, while EC use was intermediate between smoking and never-smoking.
* EC use, but not smoking or never-smoking, was significantly associated with mtCN and the cytokines IL-2 and IL-4.
* The study identified mtCN-associated methylation and gene expression in the lungs of EC users that were differentially expressed in respiratory diseases, including genes involved in cellular movement, inflammatory response, metabolism, and airway hyperresponsiveness.
* The study used bronchoscopy biospecimens from healthy EC users, smokers, and never-smokers and assessed associations of mtCN with mtDNa point mutations, immune responses, nuclear DNa methylation, and gene expression using linear regression.
* Ingenuity pathway analysis was used to identify enriched pathways.
* GEO and TCGa respiratory disease datasets were used to explore the involvement of mtCN-associated signatures.
* The study was supported by the National Cancer Institute, the National heart, Lung, and Blood Institute, the Food and Drug administration Center for Tobacco Products, the National Center For advancing Translational Sciences, and Pelotonia Intra-mural Research Funds.

Main Message:
The study suggests that smoking may elicit a lung toxic effect through mtCN, and while the impact of EC is not clear, EC-specific associations of mtCN with nuclear biomarkers indicate that exposure may not be harmless. Further research is needed to understand the role of smoking and EC-related mtCN on lung disease risks.

Mori KM, McElroy JP, Weng DY, et al. Lung mitochondrial DNa copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers. EBioMedicine. 2022;85:104301. doi:10.1016/j.ebiom.2022.104301