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

项目总结/摘要 电子烟（电子烟）的部件和零件，如电池和电子烟液，在《电子烟条例》的范围内。 食品药品监督管理局的监管机构。然而，在对以下问题的理解方面存在重大差距： 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， 包括短期的心血管影响。电子烟功率是气溶胶的重要决定因素 生成，尼古丁输送以及电子烟气溶胶中产生的有毒物质的类型和数量，但 功率对这些心血管效应的影响尚未被描述。此外，E- 香烟液体（电子液体）pH值对全身尼古丁吸收率、尼古丁诱导的交感神经 系统刺激和心率增加是心血管疾病的危险因素，目前尚不清楚。有 对加热烟草的加热非燃烧（HNB）产品对健康的影响也缺乏类似的知识 没有燃烧。预计HNB产品将与传统卷烟和电子烟竞争。 香烟菲利普莫里斯产品公司已经向FDA提交了销售其HNB产品iQOS的申请， 作为一种改良的风险烟草产品在美国之间的心血管疾病风险的差异e- 香烟和HNB产品不详。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的影响，毒性挥发物的全身暴露 有机化合物（VOCs），和短期心血管效应;（2）确定的影响的变化， 液体pH值对尼古丁药代动力学、心血管和电子烟的主观影响;以及（3）比较 尼古丁药理学、毒性VOC全身暴露和短期心血管效应的差异 用于加热而非燃烧烟草产品。这些目标将通过三个学科内 交叉人体药理学研究，每个目的一项研究，将在医院进行 健康的电子烟和/或iQOS使用者的研究病房。功率和电子液体pH值将在 目标1和2，终点将是心血管疾病风险的标志物。第三个目标将 是一个受试者内比较有毒物质暴露和心血管影响的电子烟相比， iQOS。这项对健康影响的研究将有助于了解电子烟特性的影响 关于其短期心血管效应，以及电子烟与iQOS相比的心血管效应， UCSF TCORS综合主题的一部分，即“了解综合健康影响，行为， 影响分析将提供可采取行动的信息，用于监管和公众宣传当前的 和新兴烟草产品。”这些研究将为FDA提供详细和具体的信息， 电子烟的短期心血管效应，以告知电子烟功率水平的调节和特定的 电子液体特性（pH值），以及告知FDA对新兴HNB产品的监管。

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.