Measuring Anatalline and Nicotelline to Differentiate Non-combusted Tobacco Use Using the PATH Study

使用 PATH 研究测量 Anatalline 和 Nicotelline 以区分非燃烧烟草的使用

• 批准号: 10220009
• 负责人: Kathryn Claire Edwards
• 金额: $ 22.68万
• 依托单位: WESTAT, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220009
• 关键词: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; Address; Adult; Alkaloids; Analysis of Variance; Behavior; Biological Markers; Cessation of life; Cigarette; Cigarette Smoker; Communities; Data; Development; Disease; Distal; Electronic cigarette; Exposure to; Family Smoking Prevention and Tobacco Control Act; Goals; Health; House Dust; Human; Literature; Measures; Minor; Mission; Nicotine; Nitrosamines; Oral Tobacco; Parents; Particulate Matter; Pattern; Pilot Projects; Population Assessment of Tobacco and Health; Public Health; Publishing; ROC Curve; Regulation; Research; Research Priority; Respondent; Risk; Sampling; Smokeless Tobacco; Smoker; Specimen; Time; Tobacco; Tobacco smoke; Tobacco use; Toxic effect; United States; United States Food and Drug Administration; Urine; Validation; aged; anatalline; authority; base; carcinogenicity; cigarette smoke; cigarette smoking; cigarette user; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; environmental tobacco smoke exposure; indexing; non-smoker; novel marker; polytobacco; polytobacco use; programs; smokeless tobacco use; smokeless tobacco user; snuff; snus; tobacco exposure; tobacco products; tobacco regulation; tobacco smokers; tobacco user; tool

PROJECT SUMMARY Although tobacco use remains the leading preventable cause of disease and death in the United States, all tobacco products do not confer similar public health risk. Specifically, combusted products tend to be viewed as more harmful than non-combusted products. One research priority for the Food and Drug Administration (FDA) is to better understand product toxicity including the development and validation of new biomarkers related to non-cigarette tobacco exposure, harm, or toxicity. Biomarkers that are able to distinguish between types of product use are vital to track the impact of regulatory action and associated proximal and distal health effects related to product use. The goal of this study is to measure nicotelline, a minor tobacco alkaloid associated with tobacco smoker particulate matter, in urine biospecimens from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study. Aims include to validate nicotelline and its utility (alone or in combination with other biomarkers of tobacco exposure) to distinguish combusted product use (i.e., cigarettes) from non-combusted product use (i.e., smokeless tobacco [SLT] and electronic cigarettes [e-cigarettes]). Previous research has shown when taken as a ratio with its parent compound (anatalline), nicotelline has shown promise in distinguishing SLT use from combusted tobacco use. Therefore, we propose to expand on this existing literature by measuring these compounds in a large sample (N= 140 each) of exclusive daily SLT users, exclusive daily cigarette smokers, and dual SLT + cigarette users to: (1a) validate anatalline/nicotelline ratio to distinguish exclusive SLT users from exclusive cigarette smokers, and (1b) determine anatalline/nicotelline ratio cut-points to distinguish exclusive SLT, dual SLT + cigarette use, and exclusive cigarette use. In addition, we propose exploring if this biomarker may also be able to differentiate other non- combusted product use, specifically e-cigarettes, from combusted product use. We propose additional specific aims among exclusive e-cigarette users (N= 140), and dual e-cigarette + cigarette users (N= 140): (2a) measure nicotelline to distinguish exclusive e-cigarette users from exclusive cigarette smokers, and (2b) determine cut-points of nicotelline and ratios of nicotelline-to-traditional tobacco biomarkers (i.e., 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) to distinguish exclusive e-cigarette, dual e-cigarette + cigarette use, and exclusive cigarette use. All aims will be evaluated by comparing levels of exposure using nonparametric Kruskal-Wallace analysis of variance (Aim 1a, 2a) and calculating Receiver Operating Curve (ROC) characteristics (Aim 1b, 2b) to determine cut-points for distinguishing different tobacco product use. Based on biospecimen availability online, https://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/pathstudy- biospec-index.html, these specimens should be available in sufficient quantities. Given the diversity of tobacco products and the different patterns of product use, new tools are needed to help discriminate use of one tobacco product from another and also to identify patterns of polytobacco use.

项目概要 尽管烟草使用仍然是美国疾病和死亡的主要可预防原因，但所有 烟草制品不会带来类似的公共卫生风险。具体来说，燃烧的产物往往被视为 比未燃烧的产品更有害。美国食品药品监督管理局的一项研究重点 （FDA）是为了更好地了解产品毒性，包括新生物标志物的开发和验证 与非香烟烟草接触、伤害或毒性有关。能够区分的生物标志物 产品使用类型对于跟踪监管行动的影响以及相关的近端和远端健康至关重要 与产品使用相关的影响。本研究的目的是测量尼古丁碱（一种次要烟草生物碱） 第一波人口的尿液生物样本中与吸烟者颗粒物相关 烟草与健康（PATH）研究评估。目的包括验证尼古丁及其效用（单独或联合使用） 与烟草暴露的其他生物标志物相结合）来区分燃烧产品的使用（即香烟） 来自非燃烧产品的使用（即无烟烟草 [SLT] 和电子烟 [电子香烟]）。 先前的研究表明，当以其母体化合物（anatalline）的比例计算时，尼古丁碱具有 在区分无烟烟草的使用和燃烧烟草的使用方面显示出了希望。因此，我们建议扩大 该现有文献通过在独家每日 SLT 的大样本（每个 N = 140）中测量这些化合物 用户、每日吸烟者和双 SLT + 香烟用户：(1a) 验证 anatalline/nicotelline 区分专门的 SLT 使用者和专门的吸烟者的比率，以及 (1b) 确定 anatalline/nicotelline 比例切点来区分独家 SLT、双重 SLT + 香烟使用和独家 香烟的使用。此外，我们建议探索该生物标志物是否也能够区分其他非 燃烧产品的使用，特别是电子烟，来自燃烧产品的使用。我们建议额外的具体 针对纯电子烟用户（N= 140）和双重电子烟+香烟用户（N= 140）的目标： (2a) 测量尼古丁碱以区分专门的电子烟使用者和专门的卷烟吸烟者，以及 (2b) 确定尼古丁碱的切点以及尼古丁碱与传统烟草生物标志物的比率（即 4- (甲基亚硝基氨基)-1-(3-吡啶基)-1-丁醇[NNAL])区分专属电子烟、双电子烟+ 吸烟和专门吸烟。所有目标都将通过比较暴露水平来评估 非参数 Kruskal-Wallace 方差分析（目标 1a、2a）并计算接收者操作曲线 （ROC）特征（目标 1b、2b）以确定区分不同烟草产品使用的切点。 基于在线生物样本的可用性，https://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/pathstudy- biospec-index.html，这些样本应该有足够的数量。鉴于烟草的多样性 产品和产品使用的不同模式，需要新的工具来帮助区分一种产品的使用 还可以识别多种烟草的使用模式。