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，烟草行业通过操纵香烟中的尼古丁来促进吸烟。他们现在紧随其后 同样的策略也适用于电子烟(ECs)，操纵尼古丁浓度和形态的维度， 最近开始通过使用合成尼古丁来操纵同分异构体的组成。这些 操纵导致ECs具有更好的适口性和尼古丁输送，最大限度地提高它们的吸引力和 上瘾，特别是对年轻人。而对于吸烟者来说，ECS可能是一个危害较小的选择 在年轻人中完全改变，EC的吸收，使用和上瘾是令人震惊的。 俄亥俄州立大学烟草管制科学中心的最新研究成果是：“翻转剧本”：使用 行业尼古丁攻略，最大限度地促进公共健康。J UST：烟草业操纵尼古丁 为了创造吸引年轻人的ECS，我们假设FDA， 通过尼古丁调节，可以使产品 对年轻人没有吸引力，同时仍为吸烟者提供危害较小的、有足够吸引力的替代方案 和满足感。为了检验这一假设，项目1(P1) 将研究尼古丁的独特和联合作用 形态、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 确定要求最低游离基(FB)尼古丁(尼古丁形式)含量的EC产品标准是否 减少ECS对年轻人的吸引力，但不是老年人吸烟者的吸引力(研究2)。在研究1中，使用双倍- 年轻人(21-24岁)专属EC吸毒者，无/最少吸烟史和 年长的成年吸烟者会吸出实验室准备的、不同尼古丁的烟草味液体。 尺寸。结果将包括主观效应、尼古丁药代动力学和吞噬地形。 盲目交叉设计， (25年) 至 评估不同EC尼古丁维度的毒理学影响，地形数据将用于喷烟回放 体外气液界面暴露对癌症、心血管和呼吸系统疾病的毒理学研究 代孕标记。尼古丁异构体可能有不同的代谢途径和速率，所以我们还将检查 尼古丁代谢率。在研究2中， 青少年专属EC吸烟者，吸烟史最少/没有吸烟史 老年吸烟者将在2岁时完成一次访问、双盲、随机交叉试验，服用电子烟液体 尼古丁浓度和2个异构体比率，用不同的FB尼古丁组分来评估上诉的结果。 第一节 具有重大意义和创新性，因为它将是第一个系统地研究尼古丁的影响 各维度(包括同分异构体组成)对EC滥用责任的影响，比较药理学、毒理学和 尼古丁同分异构体在人体内的代谢情况，并确定限制FB尼古丁成分的法规 在欧共体中，液体适用于保护公众健康。 与P3-4整合，结果也将通知 降低吸引力并劝阻年轻人和非使用者但不是成年人使用EC的营销和产品法规 吸烟者。P1将涉及FDA的科学领域 产品组成和设计，成瘾， 毒性、对健康的影响和行为。