Project 1: Manipulating E-cigarette Nicotine to Promote Public Health

项目一：操控电子烟尼古丁促进公众健康

基本信息

批准号：
10666067
负责人：
Theodore Lee Wagener
金额：
$ 59.8万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-14 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10666067
关键词：
21 year old Acclimatization Address Adult Air Behavior Behavioral Blood specimen Cardiovascular Diseases Cardiovascular system Cell Culture Techniques Cell Cycle Cell Proliferation Chemicals Cigarette Cigarette Smoker Cotinine Cross-Over Trials Crossover Design Data Dimensions Double-Blind Method Drug Kinetics Elderly Electronic cigarette Endothelial Cells Epithelium Exposure to Fostering Health Hour Human In Vitro Industry Inhalation Isomerism Liquid substance Malignant Neoplasms Malignant neoplasm of lung Manufacturer Marketing Measures Metabolic Metabolism Methods Modeling Modernization Nicotine Ohio Outcome Outcome Assessment Participant Pattern Persons Population Public Health Randomized Reactive Oxygen Species Regulation Research Respiratory Disease Risk Route Salts Science Smoker Smoking Smoking History Stereoisomer Surrogate Markers Testing Tobacco Tobacco Industry Toxic effect Toxicology Universities Visit Youth abuse liability addiction animal data base blind cancer biomarkers cancer risk cardiovascular endothelium combustible cigarette cytotoxicity design e-cigarette aerosols electronic cigarette use electronic cigarette user electronic liquid human data hydroxycotinine innovation metabolic profile metabolic rate nicotine use pharmacologic respiratory satisfaction senescence stem tobacco flavor tobacco products tobacco user toxicant transcriptome sequencing uptake vaping young adult

项目摘要

PROJECT SUMMARY – PROJECT 1 Historically, the tobacco industry manipulated nicotine in cigarettes to promote smoking. They are now following the same playbook for e-cigarettes (ECs), manipulating the nicotine dimensions of concentration and form, and more recently have begun manipulating isomer composition through the use of synthetic nicotine. These manipulations have led to ECs with increased palatability and nicotine delivery, maximizing their appeal and addictiveness, particularly to young people. While ECs may be a less harmful alternative for smokers who completely switch, EC uptake, use, and addiction among young people is alarming.The overall integrative theme of The Ohio State University Tobacco Center for Regulatory Science is: “Flipping the Script”: Using the Industry's Nicotine Playbook to Maximize Public Health. J ust as the tobacco industry manipulates nicotine to create ECs that appeal to young people, we posit that the FDA, through nicotine regulation, can make products unappealing to young people while still providing smokers with a less harmful alternative with sufficient appeal and satisfaction. To test this hypothesis, Project 1 (P1) will examine the unique and combined effects of nicotine form, concentration, and isomer on EC product appeal, abuse liability, use patterns, and toxicity (Study 1), and determine if an EC product standard requiring a minimum level of free-base (FB) nicotine (nicotine form) would reduce the appeal of ECs for young adults but not older adult smokers (Study 2). In Study 1, using a double- young adult (21-24 years) exclusive EC users with no/minimal history of smoking and older adult cigarette smokers will vape 8 lab-prepared, tobacco-flavored liquids varied by nicotine dimensions. Outcomes will include subjective effects, nicotine pharmacokinetics, and puffing topography. blind crossover design, (25 years) To assess the toxicological effects of varying EC nicotine dimensions, topography data will be used in puff-playback toxicology studies with in vitro air-liquid interface exposures for cancer, cardiovascular and respiratory disease surrogate markers. Nicotine isomers may have different metabolic routes and rates, so we will also examine nicotine metabolism rate. In Study 2, young adult exclusive EC users with minimal/no history of smoking and older adult smokers will complete a single-visit, double-blind, randomized crossover trial to vape e-liquids at 2 nicotine concentrations and 2 isomer ratios, with varying FB nicotine fractions to assess outcomes of appeal. P1 is significant and innovative because it will be the first to systematically examine the impact of nicotine dimensions (including isomer composition) on EC abuse liability, compare pharmacological, toxicological, and metabolic profiles of nicotine isomers in humans, and determine whether regulations limiting FB nicotine fraction in EC liquids are appropriate for the protection of public health. Integrated with P3-4, results will also inform marketing and product regulations that reduce appeal and dissuade EC use in youth and non-users but not adult tobacco users. P1 will address the FDA scientific domains of Product Composition and Design, Addiction, Toxicity, Health Effects, and Behavior.

项目摘要 – 项目 1 从历史上看，烟草业操纵香烟中的尼古丁来促进吸烟，现在他们正在效仿。与电子烟（EC）相同的剧本，操纵尼古丁的浓度和形式，最近开始通过使用合成尼古丁来操纵异构体组成。操作导致 EC 的适口性和尼古丁释放量增加，最大限度地提高了它们的吸引力和成瘾性，尤其是对年轻人来说，而电子烟对于吸烟者来说可能是一种危害较小的替代品。彻底转变，年轻人对EC的吸收、使用和成瘾令人震惊。整体整体主题俄亥俄州立大学烟草监管科学中心的研究成果是：“翻转脚本”：使用业界最大限度提高公众健康的尼古丁手册。就像烟草业操纵尼古丁一样为了创建吸引年轻人的 EC，我们认为 FDA，通过尼古丁调节，可以使产品对年轻人没有吸引力，但仍然为吸烟者提供了一种危害较小且具有足够吸引力的替代品为了检验这一假设，项目 1 (P1) 将研究尼古丁的独特和综合作用形式、浓度和异构体对 EC 产品吸引力、滥用倾向、使用模式和毒性的影响（研究 1），以及确定要求游离碱 (FB) 尼古丁（尼古丁形式）最低水平的 EC 产品标准是否会降低 EC 对年轻人的吸引力，但不会降低老年吸烟者的吸引力（研究 2）。没有/极少吸烟史的年轻成人（21-24 岁）专属 EC 用户老年吸烟者将吸食 8 种实验室制备的烟草味液体，其中尼古丁各不相同结果将包括主观效果、尼古丁药代动力学和抽吸地形。盲目交叉设计， (25岁) 到评估不同 EC 尼古丁尺寸的毒理学效应，地形数据将用于抽吸回放癌症、心血管和呼吸系统疾病的体外气液界面暴露毒理学研究替代标记物。尼古丁异构体可能具有不同的代谢途径和速率，因此我们还将进行检查。在研究 2 中，尼古丁代谢率。具有极少/无吸烟史的年轻成人专属 EC 用户，并且老年吸烟者将在 2 点完成一项针对电子烟液体的单次访问、双盲、随机交叉试验尼古丁浓度和 2 种异构体比率，以及不同的 FB 尼古丁分数来评估上诉结果。 P1 具有重要意义和创新性，因为它将是第一个系统地研究尼古丁影响的项目 EC滥用倾向的维度（包括异构体组成），比较药理学、毒理学和人类尼古丁异构体的代谢特征，并确定是否限制调节 FB 尼古丁分数 EC 液体中的含量适合保护公众健康。与 P3-4 集成，结果还将告知营销和法规产品可降低吸引力并劝阻青少年和非使用者而非成年人使用 EC P1 将涉及 FDA 的科学领域。产品成分和设计、成瘾、毒性、健康影响和行为。