Abstract 4030: Nasal gene expression reflects the physiologic response to alternate tobacco products.
Authors: Hijazi Kahkeshan , Malyszko Bozena , Steiling Katrina , Zhang Xiaohui , Liu Gang , Alekseyev Yuriy , Xiao Ji , Dumas Martine , Hertsgaard Louise , Jenson Joni , Rohde Cindy , Isaksson Rachel , Hatsukami Dorothy , Hecht Stephen , Brooks Daniel , Lenburg Marc , Spira Avrum 
Published: August 2014

Abstract
Rationale:
Potentially reduced exposure products (PREPs) are tobacco-based products that may reduce exposure to the toxins found in tobacco and thereby potentially reduce tobacco-exposure related harm. There is an urgent need to develop approaches for evaluating the biological impact of these products to determine their potential health risks. We have shown that gene expression profiling of intra- and extra-thoracic airway epithelium can serve as an indicator of physiological responses to cigarette smoke exposure. Our goal here is to establish whether this same approach might identify similarities and differences in the response to reduced exposure tobacco products. We therefore sought to determine whether the gene-expression alterations upon switching from traditional cigarettes to reduced nicotine product (0.09 mg nicotine yield XODUS) could be detected in readily collected nasal epithelium.
Methods:
Nasal epithelial brushings were obtained from 13 active smokers who switched to XODUS cigarettes for 6 weeks and then became cigarette free for the remaining 18 weeks. Nasal brushings were obtained at baseline and at 4, 6, 16, and 24-weeks. Self-report was used to determine cigarette use at baseline, 4 and 6 weeks,and self-report and alveolar CO verified cigarette abstinence at 16 and 24 weeks. RNA from the nasal brushings was processed and hybridized to Gene 1.0 ST Arrays. Gene expression alterations at each time point were identified using a linear mixed effects model among a set of 78 genes that we previously found to be altered following smoking cessation.
Results:
The expression levels of 17 of the 78 smoking cessation-associated genes changed when individuals switched from usual brand cigarettes to Xodus for 6 weeks (P&lt;0.05). XODUS usage resulted in expression levels intermediate between the normal smoking and no smoking time points for several of these genes including CYP1A1 and CYP1B1. These genes were enriched in biological categories including steroid hormone biosynthesis.
Conclusion:
Our data suggests that some of the gene expression differences induced by switching to the PREP product are intermediate between normal cigarette smoking and cigarette abstinence, consistent with the idea that these products result in reduced exposure. Our study further demonstrates that the nasal epithelium can serve as a minimally invasive tool to measure the responses to alternative tobacco products and can be leveraged to understand the underlying biological mechanisms that are similar and different from smoking-cessation.
Citation Format: Kahkeshan Hijazi, Bozena Malyszko, Katrina Steiling, Xiaohui Zhang, Gang Liu, Yuriy Alekseyev, Ji Xiao, Martine Dumas, Louise Hertsgaard, Joni Jenson, Cindy Rohde, Rachel Isaksson, Dorothy Hatsukami, Stephen Hecht, Daniel Brooks, Marc Lenburg, Avrum Spira. Nasal gene expression reflects the physiologic response to alternate tobacco products. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4030. doi:10.1158/1538-7445.AM2013-4030