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.

项目摘要 R21的总体目标“最大化现有的生物循环收集的科学价值” 应用是利用烟草产品用户的生物群体支气管肺泡灌洗（BAL）样品 通过生物标志物结果从燃烧到未燃烧的烟草的过渡的影响。 慢性烟草使用是美国发病率和死亡率的主要预防原因 关于吸烟的影响，已经建立了工作的工作很少。 切换到最近普及的电子尼古丁输送系统（末端）。这些产品的产生较少 并减少了有毒的副产品，并被晋升为吸烟的安全替代品。这些减少 有害化学含量导致气道毒性在吸烟史的背景下降低 是我们研究的重点。我们提出的实验利用气道分泌样本，目的是用户 从吸烟，吸烟者，从不吸烟者和前吸烟者中转换出来评估产品的影响 使用过渡。该评估将基于一些已建立的蛋白质生物标志物结果，并与 识别新型过渡特定生物标志物的潜力。实际上，我们以前的一项研究表明 结束了在6个月前放弃吸烟的用户，在 与吸烟者和非吸烟者相比，痰液样品表明嗜中性粒细胞死亡率更高。 该提案将专门研究从燃烧到未燃烧的烟草的过渡的影响 通过检查烟道使用气道生物标志物（例如炎症和排毒），在气道上使用 蛋白质增加有关烟草产品过渡效应影响的知识。具体目的重点 在使用UNC下收集的生物群烟草产品用户支气管肺泡灌洗（BAL）样品 TCORS和螺旋学计划在利用全面的蛋白质组学筛选技术下。目的 1检查了从燃烧到未燃烧的烟草产品使用的过渡的气道效应， 分泌的蛋白质组和胡椒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 对于以前的吸烟者以及目前，从未吸烟的人。 AIM 2调查气道中的加合物/修改 在同一用户组中的分泌样本。因此，我们将确定生物群体中的蛋白质加合物 使用靶向和未靶向的LC-MS/MS修饰蛋白质组学的样品。描述的方法 该建议不仅提供了烟道使用过渡的全面气道粘液生物标志物筛查，而且还提供 这也是分别识别产品切换或双重使用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过渡相关的健康影响的变化 气道生物标志物表示 安全。