The Impact of Acute Smoking on Airway Gene-Expression

Abstract

SESSION TITLE: Hot Topics in COPD SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 27, 2015 at 11:00 AM - 12:15 PM PURPOSE: We have previously reported gene expression changes in the bronchial airway epithelium in active smokers with longterm exposure to tobacco smoke. However, knowledge regarding the acute effects of smoking is still lacking. In this study we sought to describe the acute effects of smoking on airway epithelium gene expression. METHODS: Sixty-three individuals who are occasional light smokers without recent exposure to tobacco smoke (had not smoked a cigarette in at least 10 days) had airway epithelial cells collected from the mainstem bronchus by bronchoscopy, at baseline and at 24 hours after smoking three cigarettes. RNA isolated from the samples were processed and hybridized to Affymetrix Human Gene 1.0 ST microarrays. Gene expression differences between the baseline and post-smoking samples were assessed using a paired t-test. Enrichment of previously published smoking-related gene-expression signatures and biologic pathways were determined using Gene Set Enrichment Analysis (GSEA). RESULTS: We identified 80 genes which were differentially expressed between the baseline and post-smoking samples (FDR < 0.25). Forty-eight of the genes were induced by smoking and were related to cell survival, anti-apoptosis, xenobiotic metabolism, oxidant response, and innate immunity. Furthermore, we found that genes that change with acute exposure to tobacco smoke were enriched among genes that we previously identified as changing among chronic active smokers (GSEA FDR < 0.05). CONCLUSIONS: Acute exposure to as little as three cigarettes induces gene-expression alterations in the bronchial airway epithelium that resemble some of the changes seen in the airway of chronic active smokers. CLINICAL IMPLICATIONS: Understanding the similarity and differences between the biological effects of acute and chronic tobacco smoke exposure may have implications for understanding the pathogenesis of diseases associated with chronic tobacco exposure such as COPD and lung cancer. DISCLOSURE: The following authors have nothing to disclose: Ehab Billatos, Yaron Gesthalter, Nick ten Hacken, Dirkje Postma, Irene Heijink, Wim Timens, Corry-Anke Brandsma, Alen Faiz, Maarten Berge, Marc Lenburg, Avrum Spira No Product/Research Disclosure Information