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

项目总结 尽管烟草使用仍然是美国可预防的疾病和死亡的主要原因，但所有 烟草产品不会带来类似的公共健康风险。具体地说，燃烧的产品往往会被查看 比未燃烧的产品更有害。美国食品和药物管理局的一项研究重点 (FDA)是为了更好地了解产品毒性，包括开发和验证新的生物标记物 与非香烟烟草接触、危害或毒性有关的。生物标记物能够区分 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 与产品使用相关的效果。这项研究的目的是测量尼古丁，一种次要的烟草生物碱。 与烟草吸烟者颗粒物有关的第一波人群中的尿液生物检疫 烟草与健康评估(PATH)研究。目的包括验证尼古丁及其效用(单独或在 与烟草暴露的其他生物标志物相结合)，以区分燃烧产品的使用(即香烟) 非燃烧产品的使用(即无烟烟草[SLT]和电子烟[电子烟])。 先前的研究表明，当尼古丁与其母化合物(纳米晶)的比例时，尼古丁 在区分SLT使用和燃烧烟草使用方面显示出希望。因此，我们建议在以下方面进行扩展 这一现有文献通过在独家每日SLT的大样本(每个样本N=140)中测量这些化合物 吸烟者、独家每日吸烟者和双SLT+吸烟者：(1A)验证鼻烟/尼古丁 区分非吸烟者和吸烟者的比率，以及(1b)确定 区分单纯性SLT、双重SLT+香烟和独占性SLT的鼻咽癌/尼古丁比率切点 香烟的使用。此外，我们建议探索这一生物标志物是否也能够区分其他非 燃烧的产品使用，特别是电子烟，来自燃烧的产品使用。我们提出了额外的具体建议 针对纯电子烟使用者(N=140)和双重电子烟+香烟使用者(N=140)： (2a)测量尼古丁含量，以区分电子烟专用用户和专用香烟吸烟者；以及 (2B)确定尼古丁的切点和尼古丁与传统烟草生物标记物的比率(即4- (甲基亚硝氨基)-1-(3-吡啶)-1-丁醇[NNAL])区分独家电子烟、双电子烟+ 香烟的使用，和专属的香烟使用。所有目标将通过比较暴露水平来评估，使用 非参数Kruskal-Wallace方差分析(目标1a、2a)和计算接收器工作曲线 (ROC)特征(目标1b、2b)，以确定区分不同烟草产品用途的切入点。 基于在线可获得的生物胺，https://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/pathstudy- Biospec-index.html，这些标本应该有足够数量。鉴于烟草的多样性 产品和不同的产品使用模式，需要新的工具来帮助区分其中一种 从另一种烟草产品中获得烟草产品，并确定多种烟草的使用模式。

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.