Clinical Pharmacology of Electronic Cigarettes

项目概要/摘要 本提案是我们研究“临床药理学”的竞争性更新申请的重新提交。 电子烟”。FDA认为电子烟（EC）是烟草产品， 根据2009年《家庭吸烟预防和烟草控制法》，中 与FDA法规相关的特征是EC的成瘾性和潜在危害，两者都是 基本上取决于尼古丁的作用。EC的监管可能包括器械的监管 功率、线圈和芯的性质以及EC液体的组成。一个尚未解决的关键监管问题是 是否应该限制电子烟液的尼古丁含量。 根据尼古丁滴定在EC用户的证据，我们质疑的主张，设置上限为 电子烟液的尼古丁含量将有益于正在转向EC以帮助戒烟的吸烟者的健康 smoking.我们假设相反-即EC用户将滴定他们的尼古丁摄入量， 使用高浓度的尼古丁，会吸入相若的尼古丁量，但较少吸入有毒的气溶胶，对健康的危害亦较少。 与尼古丁含量较低的电子烟相比。因此，我们建议研究全身尼古丁暴露;尼古丁相关 主观、心血管（CV）和激素效应;暴露于非尼古丁毒物（挥发性有机 化合物，如丙烯醛和苯）;以及转换EC使用者中CV疾病（CVD）风险的生物标志物 从低尼古丁含量到高尼古丁含量的电子烟。如果我们假设使用高尼古丁会降低潜在风险， 如果证实了ECs浓度，这将表明联邦法规没有对尼古丁设定上限 在某些情况下，监管机构可能会促进使用更高而不是更低的尼古丁液体， 安全的原因。

PROJECT SUMMARY/ABSTRACT This proposal is a resubmission of a competing renewal application for our study, “Clinical Pharmacology of Electronic Cigarettes”. The FDA has deemed electronic cigarettes (EC) to be tobacco products that are to be regulated as such under the 2009 Family Smoking Prevention and Tobacco Control Act. Among the characteristics that are relevant to FDA regulation are the addictiveness and potential harm of ECs, both of which are determined in substantially by effects of nicotine. Regulations of ECs could include regulation of the device power, nature of coils and wicks, and the composition of EC liquids. A critical unresolved regulatory issue is whether there should be limit on the nicotine content of e-liquids. Based on evidence of nicotine titration in EC users, we question the proposition that setting an upper limit for nicotine content of e-liquids will benefit the health of smokers who are switching to EC to aid quitting cigarette smoking. We hypothesize the opposite – namely that EC users will titrate their intake of nicotine such that they will inhale similar amount of nicotine but fewer aerosol toxicants and suffer less harm to health when using higher vs lower nicotine content e-liquids. Thus, we propose to study systemic nicotine exposure; nicotine-related subjective, cardiovascular (CV) and hormonal effects; exposure to non-nicotine toxicants (volatile organic compounds, such as acrolein and benzene); and biomarkers of CV disease (CVD) risk in EC users switched from low to high nicotine content e-liquids. If our hypothesis of lower potential risk with use of high nicotine concentration ECs is confirmed, it would suggest that federal regulation not place an upper limit on nicotine content, and that regulators might in some cases promote the use of higher rather than lower nicotine liquids for reasons of safety.