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

基于气道生物标志物的燃烧型烟草向非燃烧型烟草使用过渡效果的评估

• 批准号: 10506004
• 负责人: Boris Reidel
• 金额: $ 19.44万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-29 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10506004
• 关键词: 2-butenal; Acetaldehyde; Acrolein; Aldehydes; Bioinformatics; Biological Markers; Bronchoalveolar Lavage; Cell Death; Cells; Chemicals; Chronic; Chronic lung disease; Cigarette; Collection; Cysteine; Data; Disease; Drug Metabolic Detoxication; Electronic Nicotine Delivery Systems; Exposure to; Future; Goals; Health; Human; Hydration status; Impairment; In Vitro; Inflammation; Inflammatory; Innate Immune Response; Knowledge; Lead; Liquid Chromatography; Liquid substance; Lung; Measurement; Migration Inhibitory Factor; Modification; Morbidity - disease rate; Mucous body substance; Nasal Epithelium; Nicotine; Outcome; Oxidation-Reduction; Palate; Pathway Analysis; Peptides; Post-Translational Protein Processing; Property; Protein Secretion; Proteins; Proteome; Proteomics; Regulation; Safety; Sampling; Smoke; Smoker; Smoking; Smoking History; Sputum; Stress; Surface; Techniques; Testing; Tissues; Tobacco use; Toxic effect; Uncertainty; United States; adduct; airway epithelium; airway inflammation; antimicrobial; base; biobank; bronchial mucus; cigarette smoke; cigarette smoking; cytokine; experimental study; former smoker; mortality; neutrophil; never smoker; non-smoker; novel; novel marker; programs; protein biomarkers; respiratory health; screening; specific biomarkers; tandem mass spectrometry; tobacco products; tobacco screening; toxicant; vapor

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.

项目概要 R21 的总体目标是“最大限度地提高现有生物样本收藏的科学价值” 该应用程序是利用烟草产品使用者的生物库支气管肺泡灌洗液 (BAL) 样本来检查 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。 慢性吸烟是美国发病率和死亡率的主要可预防原因。 关于吸烟的影响已经开展了很多工作，但人们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 (ENDS)，这些产品的产量较少。 并减少有毒副产品，并被推广为更安全的吸烟替代品。 有害化学成分可减少有吸烟史背景的气道毒性影响 是我们研究的重点，我们提出的实验利用了 ENDS 用户的气道分泌物样本。 从吸烟者、吸烟者、从不吸烟者和前吸烟者转变为评估产品的效果 该评估将基于一些已建立的蛋白质生物标志物结果以及 识别新的转变特异性生物标志物的潜力事实上，我们之前的一项研究表明，目前 戒烟超过 6 个月的 ENDS 用户在 与吸烟者和非吸烟者相比，痰样本显示中性粒细胞死亡率更高。 该提案将专门研究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（例如炎症和解毒）来在气道上使用 蛋白质以增加对烟草产品转型效应的了解。具体目标重点是。 关于利用根据 UNC 收集的烟草产品生物库用户支气管肺泡灌洗 (BAL) 样本 TCORS 和 SPIROMICS 计划利用综合蛋白质组筛选技术。 1 检查从燃烧烟草制品使用过渡到使用非燃烧烟草制品对气道的影响，使用 分泌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。 相比之下，已转为 ENDS 和双重使用者的吸烟者生物库 BAL 样本的变化 目标 2 调查气道中的添加物/修饰。 因此，我们将蛋白质测定生物库 BAL 中的加合物。 使用基于靶向和非靶向 LC-MS/MS 的修饰蛋白质组学方法对样品进行分析。 该提案不仅提供了烟草使用转变的全面气道粘液生物标志物筛查，而且 这也是分别识别产品转换或双重用途的新型生物标志物的重要机会。 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的变化 由气道生物标志物指示，因此有可能为未来的烟草产品法规提供信息 安全。