Airway Biomarker Based Assessment of Combusted to Non-Combusted Tobacco Use Transition Effects

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Project Summary The overarching goal of this R21 “Maximizing the Scientific Value of Existing Biospecimen Collections” application is to utilize biobanked bronchoalveolar lavage (BAL) samples of tobacco product users to examine the effects of the transition from combusted to non-combusted tobacco use through biomarker outcomes. Chronic tobacco use is the leading preventable cause of morbidity and mortality in the U.S. While a large body of work has been established on the effects of cigarette smoking very little is known about the consequences of switching to recently popularized electronic nicotine delivery systems (ENDS). These products produce fewer and reduced toxic byproducts and are promoted as safer alternatives to smoking. Whether these reductions in harmful chemical contents lead to reduced airway toxicity effects on a background of a cigarette smoking history is the focus of our study. Our proposed experiments utilize airway secretion samples of ENDS users that switched from cigarette smoking, smokers, never smokers and former smokers to assess the effects of product use transition. This assessment will be based on some established protein biomarker outcomes, and with the potential to identify novel transition specific biomarkers. In fact, one of our previous studies showed that current ENDS users that had given up smoking more than 6 months prior, displayed a unique proteome composition in sputum samples when compared to smokers and non-smokers, pointing to higher rates of neutrophil cell death. This proposal will specifically examine the effects of transitioning from combusted to non-combusted tobacco use on the airways, by examining tobacco use airway biomarkers, such as inflammatory and detoxification proteins to increase the knowledge on the effects of tobacco product transition effects. The specific aims focus on utilizing biobanked tobacco product user bronchoalveolar lavage (BAL) samples collected under the UNC TCORS and the SPIROMICS program under utilization of comprehensive proteomic screening techniques. Aim 1 examines the airway effects of the transition from combusted to non-combusted tobacco product use, using secreted proteome and peptidome profiles as biomarker outcomes. We will determine airway secretion proteome alterations in biobanked BAL samples of smokers that have transitioned to ENDS and dual users in comparison to former smokers, as well as current and never smokers. Aim 2 investigates adducts/modifications in airway secretion samples in the same user groups. Therefore, we will determine protein adducts in the biobanked BAL samples using targeted and untargeted LC-MS/MS based modification proteomics. The approach described in this proposal not only offers a comprehensive airway mucus biomarker screening of tobacco use transition, but also an important opportunity to identify novel biomarkers of product switching or dual use, respectively. Ultimately, our study will help to assess changes in health effects associated with tobacco product transition indicated by airway biomarkers and thereby has the potential to inform future regulations on tobacco product safety.