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

项目摘要 尽管烟草使用仍然是美国主要的可预防的疾病和死亡原因， 烟草制品不会对公众健康构成类似的风险。具体来说，燃烧产物往往被视为 比未燃烧的产品更有害。食品和药物管理局的一项优先研究 (FDA)更好地了解产品毒性，包括开发和验证新的生物标志物 与非香烟烟草接触、危害或毒性有关。生物标志物能够区分 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 与产品使用有关的影响。本研究的目的是测量尼古丁，一种次要的烟草生物碱 与吸烟者颗粒物相关，来自第1波人群的尿液生物标本 烟草与健康评估研究（PATH）目的包括验证尼可特灵及其效用（单独或联合给药） 与烟草暴露的其它生物标志物组合）来区分燃烧产品的使用（即，香烟） 来自非燃烧产物的使用（即，无烟烟草[香烟]和电子香烟[电子香烟]）。 先前的研究表明，当与其母体化合物（anatalline）按比例服用时， 在区分烟草使用和燃烧烟草使用方面显示出希望。因此，我们建议扩大 通过测量这些化合物在大样本（N= 140）的独家每日服用， 使用者、完全每日吸烟者和双吸+吸烟者：（1a）验证anatalline/nicotelline 比例，以区分排他性吸烟者和排他性吸烟者，以及（1b）确定 阿那他林/尼可泰林比率分界点，以区分排他性吸烟、双重吸烟+吸烟和排他性吸烟 香烟使用此外，我们建议探索这种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，从燃烧产品的使用。我们建议增加具体的 电子烟专用者（N= 140）和电子烟+香烟两用者（N= 140）的目标： (2a)测量尼古丁，以区分独家电子烟使用者和独家香烟吸烟者， (2b)确定尼古丁的分界点和尼古丁与传统烟草生物标志物的比率（即，4- （甲基亚硝胺）-1-（3-吡啶基）-1-丁醇[NNAL]）来区分专属电子烟、双重电子烟+ 香烟使用和专用香烟使用。所有目标都将通过比较暴露水平进行评估， 非参数Kruskal-Wallace方差分析（目标1a，2a）和计算接受者工作曲线 (ROC)烟草制品的特性（目标1b、2b），以确定区分不同烟草制品用途的分界点。 基于在线生物样本可用性，https://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/pathstudy- biospec-index.html，这些标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使用一个 烟草产品的区别，并确定混合烟草的使用模式。

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.