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; 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，烟草行业在香烟中操纵尼古丁以促进吸烟。他们现在正在关注 电子烟（ECS）的同一本剧本，操纵集中和形式的尼古丁维度， 最近，通过使用合成尼古丁开始操纵异构体组成。这些 操纵导致ECS的可口性和尼古丁的递送增加，使其外观最大化和 额外的，特别是对年轻人。虽然EC可能是吸烟者的危害较小的替代方案 年轻人中完全切换，EC吸收，使用和成瘾令人震惊。总体综合主题 俄亥俄州立大学烟草监管科学中心的位置是：“翻转脚本”：使用 行业的尼古丁剧本，以最大化公共卫生。 j UST作为烟草行业操纵尼古丁 为了创建对年轻人出现的EC，我们的海报是FDA， 通过尼古丁法规可以制造产品 对年轻人没有吸引力，同时仍可为吸烟者提供较小的有害替代品，外观足够 和满意。为了检验这一假设，项目1（P1） 将检查尼古丁的独特效果 EC产品外观，滥用责任，使用模式和毒性的形式，集中和异构体（研究1）和 确定EC产品标准是否需要最低水平的自由碱（FB）尼古丁（尼古丁形式） 减少年轻人而不是老年吸烟者的EC出现（研究2）。在研究1中，使用双重 年轻成人（21-24岁）独家EC用户，没有/最小的吸烟史和 老年人吸烟者将vape 8实验室准备，烟草味的液体因尼古丁而变化 方面。结果将包括主观效果，尼古丁药代动力学和浮肿地形。 盲人跨界设计， （25年） 到 评估不同EC尼古丁维度的毒理学效应，地形数据将用于Puff-playback 毒理学研究，用于癌症，心血管和呼吸系统疾病的体外空气界面暴露 替代标记。尼古丁异构体可能具有不同的代谢路线和速率，因此我们还将检查 尼古丁代谢率。在研究2中 年轻成人独家EC使用者，吸烟的历史最小/无历史 老年人吸烟者将完成一次单访，双盲的，随机的跨界试验，以vape e-liquids 2 尼古丁浓度和2个异构体比率，具有不同的FB尼古丁级分，以评估外观结果。 P1 具有重要意义和创新性，因为它将是第一个系统地检查尼古丁的影响的人 关于EC滥用责任的维度（包括异构体组成），比较药物，毒理学和 尼古丁异构体在人类中的代谢谱，并确定法规是否限制了FB尼古丁分数 在EC中，液体适合保护公共卫生。 与P3-4集成，结果还将告知 营销和产品法规减少外观并劝阻青年和非用户的EC使用，但不是成人 烟草用户。 P1将解决FDA科学领域 产品组成和设计，成瘾， 毒性，健康影响和行为。