Tobacco-Related Alterations in Airway Gene Expression are Rapidly Reversed Within Weeks Following Smoking-Cessation

Abstract

The physiologic response to tobacco smoke can be measured by gene-expression profiling of the airway epithelium. Temporal resolution of kinetics of gene-expression alterations upon smoking-cessation might delineate distinct biological processes that are activated during recovery from tobacco smoke exposure. Using whole genome gene-expression profiling of individuals initiating a smoking-cessation attempt, we sought to characterize the kinetics of gene-expression alterations in response to short-term smoking-cessation in the nasal epithelium. RNA was extracted from the nasal epithelial of active smokers at baseline and at 4, 8, 16, and 24-weeks after smoking-cessation and put onto Gene ST arrays. Gene-expression levels of 119 genes were associated with smoking-cessation (FDR < 0.05, FC ≥1.7) with a majority of the changes occurring by 8-weeks and a subset changing by 4-weeks. Genes down-regulated by 4- and 8-weeks post-smoking-cessation were involved in xenobiotic metabolism and anti-apoptotic functions respectively. These genes were enriched among genes previously found to be induced in smokers and following short-term in vitro exposure of airway epithelial cells to cigarette smoke (FDR < 0.05). Our findings suggest that the nasal epithelium can serve as a minimally-invasive tool to measure the reversible impact of smoking and broadly, may serve to assess the physiological impact of changes in smoking behavior.

Immune modulation by chronic exposure to waterpipe smoke and immediate-early gene regulation in murine lungs

“…We adopted previous approaches to show that IEGs may potentially quantify and predict harmful effects in humans, known as biomarkers of potential harm, based on the magnitude and direction of expression 140–142. Furthermore, IEG testing in the nasal epithelium and gingiva (the gums) is a promising and non-invasive alternative with clinical relevance 143 144. These results emphasise the importance of policies that support the research and development of IEGs as novel non-traditional biomarkers of newly modified tobacco products.…”

Smoking induces sex-specific changes in the small airway proteome

“…In addition, analysis of lung epithelium gene expression has shown that whereas most smoking-related changes reverse following smoking cessation, some appear to be permanent, even in long-term former smokers [17][18][19].…”

Current Smoking Alters Gene Expression and DNA Methylation in the Nasal Epithelium of Patients with Asthma

“…GSEA used datasets analyzing airway epithelial cells from patients exposed to cigarette smoke for 30 minutes four times (GSE30660) before gene expression analysis and bronchial epithelium air-liquid interface (ALI) cultures exposed cigarette smoke for 24 hours before gene expression analysis (GSE82137) (21). We conducted GSVA on a dataset that analyzed nasal epithelium gene expression from smokers who had quit smoking, over a 6-month period (GSE83364) (22). We also conducted GSVA on datasets that analyzed changes gene expression in A549 cells in which NRF2 (GSE113519) and AHR (GSE109576) (23) are inhibited.…”

“…To explore the effect of smoking cessation on genes that change with smoke exposure, we performed a GSVA using an independent in vivo nasal smoking cessation dataset (22). A subset of the 25 top significantly increased and a second subset of the 25 top significantly decreased genes in the nasal epithelium were analyzed for changes associated with smoking cessation.…”