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

• 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
• 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

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。他们现在正在跟踪 电子烟（EC）的相同剧本，操纵尼古丁浓度和形式的维度， 并且最近已经开始通过使用合成尼古丁来操纵异构体组合物。这些 操作导致EC具有增加的适口性和尼古丁递送，最大化其吸引力， 成瘾，尤其是对年轻人。虽然EC可能是吸烟者的一种危害较小的替代品， 完全转换，年轻人中的EC吸收，使用和成瘾是令人震惊的。 俄亥俄州州立大学烟草监管科学中心的研究报告是：“翻转脚本”：使用 行业的尼古丁剧本，以最大限度地提高公众健康。J 就像烟草业操纵尼古丁 为了创造吸引年轻人的EC，我们认为FDA， 通过尼古丁的调节， 对年轻人没有吸引力，同时仍然为吸烟者提供了具有足够吸引力的危害较小的替代品 和满足感为了验证这一假设，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产品的吸引力、滥用倾向、使用模式和毒性（研究1），以及 确定要求最低水平游离碱（FB）尼古丁（尼古丁形式）的EC产品标准是否 降低了年轻人而不是老年人吸烟者对EC的吸引力（研究2）。在研究1中，使用双- 年轻成年人（21-24岁），无吸烟史/吸烟史极轻微的EC专用者， 老年人吸烟者将vape 8实验室准备的，烟草味的液体，由尼古丁变化 尺寸.结果将包括主观效应、尼古丁药代动力学和抽吸地形图。 盲交叉设计， (25年）的 到 为了评估不同EC尼古丁尺寸的毒理学效应，将在抽吸回放中使用地形数据 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。尼古丁异构体可能有不同的代谢途径和速率，因此我们还将研究 烟碱代谢率在研究2中， 年轻成人专用EC使用者，有极轻微/无吸烟史， 老年吸烟者将完成一项单次访问，双盲，随机交叉试验，以vape电子液体在2 尼古丁浓度和2种异构体比例，以及不同的FB尼古丁分数，以评估上诉结果。 P1 这项研究意义重大，具有创新性，因为它将首次系统地研究尼古丁的影响， 维度（包括异构体组成）对EC滥用倾向的影响，比较药理学，毒理学和 尼古丁异构体在人体中的代谢谱，并确定是否限制FB尼古丁组分的法规 在EC液体中的使用是适当的，以保护公众健康。 与P3-4集成，结果还将告知 营销和产品法规，降低吸引力，劝阻青年和非使用者使用EC，但不包括成年人 烟草使用者P1将解决FDA的科学领域， 产品组成和设计，成瘾， 毒性、健康影响和行为。