Effects of Nicotine Concentration Levels in E-cigarettes on Biomarkers of Exposure to Toxicants and Tobacco Use Behaviors

项目摘要 电子尼古丁传递系统(Ends，或电子烟)是一种新的烟草产品类别，可能代表着 一种对可燃香烟吸烟者危害较小的替代品。2020年，3.7%(920万)的18岁成年人 和较老的报告目前使用的END。目前的日常或某一天的终端使用是最普遍的 现在吸烟者(13.8%)和以前吸烟者(13.3%)，在成年从不吸烟者中很少见 (2.2%)。E-液态尼古丁浓度水平是尼古丁传递的主要产品水平决定因素之一 和感觉运动特征，并有各种尼古丁浓度水平在末端可用。 现代蒸发产品(例如，像Juul这样的豆荚-mod风格)在盐配方中含有尼古丁，并倾向于 更有效地将尼古丁输送到肺部。最近，美国食品和药物管理局(FDA)批准了 上市前烟草产品营销审查中的几种终端产品尼古丁水平各不相同，如 作为0%(Logic Pro)、1.5%(Vuse Ciro)、3.0%(Vuse Viper)、4.5%(NJOY Daily Rich)和6.0%(NJOY Daily Extra Rich)。与此同时，FDA宣布了拟议规则的计划，以将尼古丁水平降低到最低成瘾性或 香烟中的非成瘾水平(Cig)。电子烟液尼古丁浓度水平影响的研究， 特别是不同的尼古丁水平如何与健康影响、烟草使用行为和尼古丁相关 尼古丁依赖以及尼古丁水平如何在人群水平上与蒸发设备相互作用，可能具有重要的意义 对未来烟草监管科学的影响。这项大规模的人口研究将把人口与 烟草与健康(PATH)波1-6限制性生物标记物的成人访谈评估 调查。在目标1中，我们将分析汇集的路径生物标记物-成人访谈数据，以1)检验- 不同尼古丁浓度水平(如0、低、中)的受试者暴露生物标志物(BOEs)的差异 和高)，以及2)测试尼古丁水平和蒸发产品对来自5个FDA类别的BOEs的交互作用 确定的有害和潜在有害成分(HPHC)：尼古丁代谢物、TSNAs、金属、多环芳烃、VOCs 以及使用加权多变量对尿液和血清中的健康影响(例如，氧化应激)的BOE 回归模型。在目标2中，我们将利用协调的纵波1-6路径成人访谈数据 前瞻性地研究烟头和蒸发设备中的尼古丁水平与烟草使用行为的关系 (例如，随后戒烟或随后再次吸烟)和尼古丁 依赖。这项研究的创新之处在于，它关注了电子液体尼古丁浓度水平和 蒸发设备对人群健康(生物标志物)的影响，结束↔CIG使用转变和尼古丁依赖 利用全国纵向数据。这些信息对未来的烟草有重要的影响。 人口层面的监管科学，并可以指导FDA关于未来烟草产品的上市前 应授权提交高尼古丁产品的申请(PMTA)。 1

Project Summary Electronic Nicotine Delivery System (ENDS, or e-cigarette) is a new class of tobacco products and may represent a reduced harm alternative for combustible cigarette smokers. In 2020, 3.7% (9.2 million) of adults aged 18 years and older reported current use of ENDS. Current everyday or some-day ENDS use is most prevalent among current cigarette smokers (13.8%) and former smokers (13.3%) and is uncommon among adult never smokers (2.2%). E-liquid nicotine concentration level is one of the primary product-level determinants of nicotine delivery and sensorimotor characteristics and there is a variety of nicotine concentration levels available in ENDS. Modern vaping products (e.g., pod-mod style like JUUL) contain nicotine in the salt formulation and tend to deliver nicotine to the lung more efficiently. Most recently, the Food and Drug Administration (FDA) has granted several ENDS products in the Premarket Tobacco Product Marketing review with varying nicotine levels, such as 0% (Logic Pro), 1.5% (Vuse Ciro), 3.0% (Vuse Viper), 4.5% (NJOY Daily Rich), and 6.0% (NJOY Daily Extra Rich). Meanwhile, FDA announced plans for proposed rules to reduce nicotine levels to minimally addictive or non-addictive levels among cigarettes (Cig). The research on the effects of e-liquid nicotine concentration levels, especially how different nicotine levels are related to health effects, tobacco use behaviors, and nicotine dependence and how nicotine levels interplay with vaping devices at the population level, can have important implications for future tobacco regulatory sciences. This large-scale population study will link the Population Assessment of Tobacco and Health (PATH) Waves 1-6 restricted biomarker with the PATH Adult Interview surveys. In Aim 1, we will analyze the pooled PATH biomarker-adult interview data to 1) examine between- subjects differences in biomarkers of exposure (BOEs) by nicotine concentration levels (e.g., zero, low, medium and high), and 2) test interaction effects of nicotine levels and vaping products on BOEs from 5 classes of FDA defined harmful and potentially harmful constituents (HPHC): nicotine metabolites, TSNAs, metals, PAHs, VOCs and the BOE of health effects (e.g., oxidative stress) in urine and serum panels using weighted multivariable regression models. In Aim 2, we will leverage the harmonized longitudinal Waves 1-6 PATH Adult Interview data to prospectively examine associations of nicotine levels in ENDS and vaping devices with tobacco use behaviors (e.g., subsequent abstinence from cigarette smoking or subsequent relapse to cigarette smoking) and nicotine dependence. This study is innovative in its focus on the effects of e-liquid nicotine concentration levels and vaping devices on population health (biomarkers), ENDS ↔ Cig use transitions and nicotine dependence by leveraging the nationally longitudinal data. Such information has important implications for future tobacco regulatory sciences at the population level and can guide FDA as to whether future Premarket Tobacco Product Application (PMTA) submissions for higher nicotine products should be authorized. 1