Adolescent ENDS Use, Nicotine Metabolism and Toxicant Exposure

 描述（由申请人提供）：青少年中电子尼古丁输送系统（ENDS）的使用率呈指数级增长，非传统香烟（TC）吸烟者中使用率较高。我们必须了解ENDS如何影响青少年，因为这些产品含有成瘾成分尼古丁，因此继续使用可能会促进依赖。鉴于ENDS在青少年中的快速吸收，迫切需要了解这些产品在青少年中的安全性，包括1）使用如何导致毒物暴露和2）识别使用和依赖的可能生物介质，如尼古丁代谢率。目的：我们将调查有毒物质的存在，并检查尼古丁代谢率对青少年ENDS使用者的使用行为和尼古丁依赖的影响。具体目标：调查仅使用ENDS的青少年中发现的有毒物质水平，包括环氧丙烷、丙烯醛、环氧乙烷、苯、丙烯酰胺、甲醛和1，3丁二烯（AIM 1）。检查通过唾液3 '羟基可替宁/可替宁比率测量的尼古丁代谢率与ENDS使用频率之间的相关性，并报告仅使用ENDS的青少年依赖性（AIM 2）。研究设计：采用横断面设计，180只ENDS使用青少年（13-17岁），我们将研究如何ENDS的使用有助于毒物暴露。我们还将评估个体的尼古丁代谢率是否可能是ENDS使用和依赖的生物介质。将分析仅ENDS使用者和20名年龄相似的青少年非吸烟者/非ENDS使用者的尿样中的毒木贼碱、NNAL和毒物水平。将进行ENDS行为问卷和尼古丁依赖量表。将采集唾液样本，用于测定尼古丁代谢率。仅ENDS使用将通过可替宁进行验证，并通过测量尿液阿那巴辛和NNAL与TC暴露进行区分。意义：在青少年中，ENDS的使用超过了TC的使用。因为大多数成年人在青少年时期就开始对TC上瘾，所以我们必须了解ENDS在青少年中使用的生物学影响，就像我们对TC所做的那样。拟议的研究是实现这一最终目标的重要一步，原因有几个。首先，确定青少年ENDS使用者体内的毒物负荷可以为潜在的使用者、政策制定者和临床医生提供重要的预防信息。其次，确定生物风险因素，如尼古丁代谢率，可能会促进更严重的ENDS使用和依赖，这是在这个年龄组中成功预防和ENDS戒烟干预措施的发展的一步。这项研究的结果将提供必要的试点数据，以追求纵向调查模式的青少年ENDS的使用，有毒物质的暴露，并发展的依赖。

 DESCRIPTION (provided by applicant): The prevalence of electronic nicotine delivery system (ENDS) use among adolescents is increasing exponentially, with significant use among non-traditional cigarette (TC) smokers. It is imperative that we learn how ENDS affect adolescents because these products contain the addictive ingredient nicotine, so continued use is likely to promote dependence. Given the rapid uptake of ENDS among teens, there is a critical need to understand the safety of these products in adolescents, including 1) how use contributes to toxicant exposure and 2) identification of possible biologic mediators of usage and dependence, such as the nicotine metabolic rate. Objective: We will investigate the presence of toxicants and examine the influence of the rate of nicotine metabolism on use behaviors and nicotine dependence in adolescent ENDS-only users. Specific Aims: Investigate the level of toxicants including propylene oxide, acrolein, ethylene oxide, benzene, acrylamide, formaldehyde, and 1,3, butadiene found in adolescent ENDS-only users (AIM 1). Examine the association between the rate of nicotine metabolism measured by the salivary 3'hydroxycotinine/cotinine ratio and the frequency of ENDS use and reported dependence in adolescent ENDS-only users (AIM 2). Study Design: Using a cross-sectional design with 180 ENDS-only using adolescents (13-17 years of age) we will examine how ENDS use contributes to toxicant exposure. We will also assess whether an individual's rate of nicotine metabolism may be a biologic mediator of ENDS use and dependence. Urine samples will be analyzed for anabasine, NNAL and toxicant levels in ENDS-only users and a control group of 20 similarly aged adolescent non-smokers/non-ENDS users. ENDS behavior questionnaires and nicotine dependence scales will be administered. Saliva samples will be obtained for determination of the nicotine metabolic rate. ENDS-only usage will be verified by cotinine, and differentiated from TC exposure by the measurement of urine anabasine and NNAL. Significance: The use of ENDS has surpassed use of TC among adolescents. Because most adults addicted to TCs began during adolescence, it is essential that we understand the biological impact of ENDS use in adolescents, as we have done with TCs. The proposed study is an important step toward achieving this ultimate objective for several reasons. First, determining the in vivo toxicant load in adolescent ENDS users can provide vital prevention information for prospective users, policy makers and clinicians. Second, identifying biologic risk factors, such as the nicotine metabolic rate, that may promote heavier ENDS use and dependence is a step toward the development of successful prevention and ENDS cessation interventions in this age group. Results from this study will provide the necessary pilot data to pursue longitudinal investigations into patterns of adolescent ENDS use, toxicant exposure, and development of dependence.