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

项目摘要 R21的首要目标是“最大化现有生物样品的科学价值” 应用是利用烟草制品使用者的生物库支气管肺泡灌洗(BAL)样本来检测 从燃烧烟草使用过渡到非燃烧烟草使用的影响通过生物标记物的结果。 在美国，长期吸烟是导致发病率和死亡率的主要可预防原因，而一个庞大的身体 关于吸烟的影响的工作已经建立起来，对吸烟的后果知之甚少 改用最近流行的电子尼古丁输送系统(完)。这些产品生产的产品较少 并减少有毒副产品，并作为吸烟的更安全替代品进行推广。这些削减是否会 有害化学成分可降低吸烟史背景下的呼吸道毒性效应 是我们研究的重点。我们建议的实验利用终端用户的呼吸道分泌物样本 改用吸烟者、吸烟者、从不吸烟者和曾经吸烟者评估产品的效果 使用过渡。这项评估将基于一些已建立的蛋白质生物标记物结果，并与 识别新的过渡特异性生物标记物的可能性。事实上，我们之前的一项研究表明，目前 超过6个月前戒烟的终端用户，在 与吸烟者和不吸烟者相比，痰样本表明中性粒细胞死亡率更高。 该提案将具体审查从燃烧烟草向非燃烧烟草过渡的影响。 通过检查烟草使用的呼吸道生物标志物，如炎症和解毒，在呼吸道上的使用 增加对蛋白质影响的认识，对烟草产品过渡效果的影响。具体目标和重点 关于利用生物库烟草产品使用者的支气管肺泡灌洗(BAL)样本的研究 TCORS和SPIROMICS计划利用全面的蛋白质组筛选技术。目标 1研究了从燃烧烟草制品到非燃烧烟草制品使用的转变对呼吸道的影响，使用 分泌的蛋白质组和多肽组图谱作为生物标志物的结果。我们将测定呼吸道分泌物蛋白质组 相比较而言，转变为吸烟者和双重吸烟者的生物库BAL样本的变化 给以前吸烟者，以及现在和从不吸烟者。目标2研究呼吸道中的加合物/修饰 同一用户组的分泌物样本。因此，我们将测定生物库中的蛋白质加合物 使用靶向和非靶向LC-MS/MS修饰蛋白质组学的样品。中描述的方法 这项建议不仅为烟草使用过渡提供了一个全面的呼吸道粘液生物标志物筛查，而且 也是识别产品转换或两用的新生物标记物的重要机会。 最终，我们的研究将有助于评估烟草产品转型对健康影响的变化。 由呼吸道生物标志物指示，因此有可能为未来的烟草产品法规提供信息 安全。

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.