PROJECT 2: SHORT-TERM CARDIOVSCULAR EFFECTS OF E-CIGARETTES: INFLUENCE OF DEVICE POWER AND E-LIQUID pH AND HOW E-CIGARETTES COMPARE WITH HEAT-NOT-BURN PRODUCTS

项目 2：电子烟的短期心血管影响：设备功率和电子烟液 pH 值的影响以及电子烟与加热不燃烧产品的比较

• 批准号: 10259837
• 负责人: Gideon St.Helen
• 金额: $ 42.76万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259837
• 关键词: Acceleration; Acrolein; Acute; Aerosols; Affect; Aldehydes; Area; Atomizer; Behavior; Biological Markers; Blood Circulation; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Characteristics; Cigarette; Communication; Controlled Environment; Cross-Over Studies; Dangerousness; Deposition; Devices; Drug Kinetics; Electronic cigarette; Emerging Tobacco Products; Event; Exposure to; Flavoring; Generations; Goals; Health; Heart Rate; Heating; Hospitals; Human; Inflammatory; Kinetics; Knowledge; Lung; Modified Risk Tobacco Product; Nicotine; Oral cavity; Oxidative Stress; Pharmacology; Pharmacology Study; Pharyngeal structure; Poison; Power Sources; Process; Reactive Oxygen Species; Regulation; Research; Risk; Risk Factors; Science; Sensory; Smoke; Sympathetic Nervous System; Tobacco; Tobacco Industry; Tobacco smoke; Toxicant exposure; Toxicology; United States Food and Drug Administration; absorption; alkalinity; authority; base; behavioral economics; cardiovascular disorder risk; cardiovascular effects; cardiovascular risk factor; combustible cigarette; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; electronic liquid; heated tobacco products; hemodynamics; human study; particle; thrombogenesis; tobacco products; toxicant; volatile organic compound; ward

PROJECT SUMMARY/ABSTRACT Components and parts of electronic cigarettes (e-cigarettes), such as batteries and e-liquids, are within the Food and Drug Administration's regulatory authority. There are, however, significant gaps in understanding of how specific aspects of these components and parts influence the overall health effects of e-cigarettes, including short-term cardiovascular effects. E-cigarette power is an important determinant of aerosol generation, nicotine delivery, and the type and amount of toxicants generated in e-cigarette aerosols, but the influence of power on these cardiovascular effects has not been described. In addition, the influence of e- cigarette liquid (e-liquid) pH on rate of systemic nicotine absorption, nicotine-induced sympathetic nervous system stimulation, and heart rate increase, a risk factor for cardiovascular disease, is not understood. There is a similar lack of knowledge about the health effects of heat-not-burn (HNB) products, which heat tobacco without combustion. It is expected that HNB products will compete with conventional cigarettes and e- cigarettes. Philip Morris Products S.A. has filed an application with the FDA to market its HNB product, iQOS, as a modified risk tobacco product in the U.S. Differences in the cardiovascular disease risks between e- cigarettes and HNB products are unknown. This project has three specific aims to fill these gaps: (1) Determine the impact of e-cigarette power on nicotine pharmacology, systemic exposure to toxic volatile organic compounds (VOCs), and short-term cardiovascular effects; (2) Determine the impact of changes in e- liquid pH on nicotine pharmacokinetics, cardiovascular, and subjective effects of e-cigarettes; and (3) Compare differences in nicotine pharmacology, systemic exposure to toxic VOCs, and short-term cardiovascular effects of e-cigarettes to heat-not-burn tobacco products. These aims will be achieved through three within-subject crossover human pharmacology studies, one study for each aim, which will be conducted on a hospital research ward with healthy users of e-cigarettes and/or iQOS. Power and e-liquid pH will be manipulated in aims 1 and 2, respectively, and the endpoints will be markers of cardiovascular disease risk. The third aim will be a within-subject comparison of toxicant exposure and the cardiovascular effects of e-cigarettes compared to iQOS. This study of health effects will contribute to knowledge of the influence of e-cigarette characteristics on their short-term cardiovascular effects, and the cardiovascular effects of e-cigarettes compared to iQOS as part of the UCSF TCORS integrated theme that “understanding combined health effects, behavior, and impact analysis will provide actionable information for regulation of and public communications about current and emerging tobacco products.” These studies will provide the FDA with detailed and specific information on short-term cardiovascular effects of e-cigarettes to inform regulation of e-cigarette power levels and a specific e-liquid characteristic (pH), as well as inform FDA regulation of emerging HNB products.

项目概要/摘要 电子烟（电子烟）的零部件，例如电池和烟油，均属于 然而，食品药品监督管理局的监管机构对此的认识存在重大差距。 这些组件和部件的具体方面如何影响电子烟的整体健康影响， 包括短期心血管影响。电子烟的威力是气溶胶的一个重要决定因素。 电子烟气溶胶中产生的尼古丁释放量以及有毒物质的类型和数量，但是 此外，尚未描述功率对这些心血管效应的影响。 卷烟液体（电子液体）pH值对全身尼古丁吸收率、尼古丁引起的交感神经紧张的影响 系统刺激和心率增加（心血管疾病的危险因素）尚不清楚。 对于加热烟草的加热不燃烧 (HNB) 产品的健康影响也同样缺乏了解 预计加热不燃烧产品将与传统卷烟和电子烟竞争。 Philip Morris Products S.A. 已向 FDA 提交了销售其 HNB 产品 iQOS 的申请， 在美国作为一种改良风险烟草产品 电子烟和烟草之间心血管疾病风险的差异 卷烟和加热不燃烧产品尚不清楚，该项目有三个具体目标来填补这些空白：(1) 确定电子烟功率对尼古丁药理学、有毒挥发物全身暴露的影响 有机化合物（VOC）和短期心血管影响；（2）确定电子变化的影响； 液体 pH 值对电子烟尼古丁药代动力学、心血管和主观影响的影响；以及 (3) 比较 尼古丁药理学、有毒挥发性有机化合物的全身暴露和短期心血管影响的差异 这些目标将通过三个主题内实现。 交叉人类药理学研究，每个目标一项研究，将在医院进行 电子烟和/或 iQOS 健康用户的研究病房的功率和电子液体 pH 值将被操纵。 分别是目标 1 和 2，终点将是心血管疾病风险的标志。 对电子烟的毒物暴露和心血管影响进行受试者内比较 iQOS 对健康影响的研究将有助于了解电子烟特性的影响。 其短期心血管影响，以及电子烟与 iQOS 相比的心血管影响 UCSF TCORS 综合主题的一部分是“了解健康影响、行为和健康的综合影响” 影响分析将为当前的监管和公众交流提供可操作的信息 这些研究将为 FDA 提供有关以下方面的详细且具体的信息： 电子烟的短期心血管影响，为电子烟功率水平和具体的监管提供信息 电子液体特性 (pH)，以及告知 FDA 对新兴 HNB 产品的监管。