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

项目摘要 本R21的总体目标是“最大限度地发挥现有生物标本采集的科学价值” 应用是利用烟草制品使用者的生物库支气管肺泡灌洗（BAL）样品来检查 通过生物标志物结果，从燃烧烟草使用过渡到非燃烧烟草使用的影响。 长期吸烟是美国发病率和死亡率的主要可预防原因，而大量人群 关于吸烟的影响，人们已经做了大量的工作，但对吸烟的后果却知之甚少。 转向最近流行的电子尼古丁输送系统（ENDS）。这些产品生产的 并减少有毒副产物，并被推广为吸烟的更安全的替代品。这些减少是否 有害的化学成分导致在吸烟史的背景下降低气道毒性作用 是我们研究的重点。我们提出的实验利用ENDS使用者的气道分泌物样本， 从吸烟者、吸烟者、从不吸烟者和既往吸烟者转换，以评估产品的影响 使用transition。该评估将基于一些已建立的蛋白质生物标志物结果， 有可能鉴定新的过渡特异性生物标志物。事实上，我们之前的一项研究表明， 戒烟超过6个月的ENDS使用者，显示出独特的蛋白质组组成， 痰样本相比，吸烟者和非吸烟者，指出更高的比率的中性粒细胞死亡。 该提案将具体审查从燃烧烟草过渡到非燃烧烟草的影响 通过检查烟草使用气道生物标志物，如炎症和解毒， 蛋白质，以增加对烟草产品过渡效应的认识。具体目标聚焦 使用生物库烟草产品使用者支气管肺泡灌洗（BAL）样本， TCORS和SPIROMICS计划利用综合蛋白质组学筛选技术。目的 第1章研究了从燃烧型烟草产品使用到非燃烧型烟草产品使用的过渡对气道的影响， 分泌的蛋白质组和肽组谱作为生物标志物结果。我们将确定气道分泌蛋白质组 已转换为ENDS的吸烟者和双重使用者的生物库BAL样本的变化 吸烟者，以及目前和从未吸烟者。目的2研究气道中的加合物/修饰物 分泌物样本在相同的用户组。因此，我们将测定生物样本库BAL中的蛋白加合物 使用基于靶向和非靶向LC-MS/MS的修饰蛋白质组学分析样品。中描述的方法 该建议不仅提供了烟草使用过渡的全面气道粘液生物标志物筛查， 也是一个重要的机会，以确定新的生物标志物的产品转换或双重用途。 最终，我们的研究将有助于评估与烟草产品转型相关的健康影响变化 因此有可能为未来的烟草产品法规提供信息 安全为代价的

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.