Project 2: Oxidative Stress and Harmful Constituent Levels Associated with Little Cigars

项目摘要/摘要：项目2 这个项目的总体目标是确定与小雪茄相关的毒性和危害，以及 重点测量主流烟雾排放中的氧化剂及其生物效应。该项目是 对RFA科学领域的“毒性”和“成瘾”的回应。该项目有助于形成 总体TCORS的综合主题，重点是烟草相关氧化剂和 开发可靠的产品测试方法。 小雪茄已经成为一种越来越受欢迎的烟草产品，因为它们提供价格 与传统卷烟相比具有更大的优势。然而，我们小组和烟草公司正在出现的证据 美国疾病控制中心产品实验室称，很少有雪茄比其他香烟有毒 香烟。然而，关于小雪茄的相对危害，仍有许多有待确定的问题，包括 它们对氧化应激、损伤和炎症的影响。我们的具体目标是： 目的：1.测定气相和颗粒相中的自由基和其他有害和 40种最常见的小雪茄烟雾中的潜在有害成分(羰基、多环芳烃、NNK、NNN) 机器烟协议(FTC、CI)下的品牌。产品物理和化学特性的影响 例如过滤器通风水平、棒长和烟草硝酸盐水平，这些都可以由FDA监管 当局，将根据这些选民的水平进行建模。 AIM2.确定小雪茄特征对人体接触烟草烟雾氧化剂的影响。在一个 在不同吸烟者中的平衡随机交叉研究设计，受试者将被分配到6次暴露 组。这些条件包括高氧化剂无味少量雪茄暴露条件，低氧化剂无味少量 雪茄暴露条件下，高氧化剂风味暴露条件下，低氧化剂风味暴露条件下 雪茄暴露条件，自己平时抽的香烟，以及对照条件(未点燃的小雪茄)。在吸烟之后 对于每种产品，呼出的呼吸冷凝液样本将在基线(-15)、30、60、90、120和 150分钟。样本将被分析氧化剂/炎症标志物的水平，包括过氧化氢， 8-异前列腺素和C反应蛋白，以及尼古丁、NNK和NNN。 目的3.确定当前小雪茄消费者潜在危害的生物标记物水平 其他烟草产品，包括香烟和电子烟在人口和烟草健康研究中的作用 (路径)。目标3a。使用第一波和第五波数据，我们将分析和比较潜在危害的生物标记物 包括氧化应激(8-异前列腺素)和炎症(可溶性细胞间黏附分子-1， 白介素6)。次要结果将包括其他烟草烟雾毒物和尼古丁的生物标记物。 代谢物和烟草成瘾的行为测量。目标3b。确定硝酸盐水平的影响和 潜在危害的生物标志物上的杆长。

Project Summary/Abstract: Project 2 The overall goal of this project is to determine the toxicity and harm associated with little cigars, with an emphasis on measuring the oxidants in mainstream smoke delivery and their biological effects. The project is responsive to the RFA Scientific Domains of “Toxicity” and “Addiction.” The project helps form the integrative theme of the overall TCORS that focuses on harm generated from tobacco-related oxidants and the development of reliable methods for product testing. Little cigars have become an increasingly popular tobacco product because they offer price advantages compared to traditional cigarettes. However, emerging evidence by our group and the Tobacco Products Laboratory of the Centers for Disease Control implicate little cigars as more toxic than even cigarettes. However, there is still much to be determined about the relative harm from little cigars including their effects on oxidative stress, damage and inflammation. Our specific aims are: Aim1. Determine the levels of gas phase and particulate phase free radicals and other Harmful and Potentially Harmful Constituents (carbonyls, PAHs, NNK,NNN) in the smoke of the 40 most common little cigar brands under machine-smoked protocols (FTC, CI). The effects of physical and chemical product features such as filter ventilation level, rod length and tobacco nitrate levels, which can be regulated under FDA authority, will be modelled against levels of these constituents. Aim2. Determine the effects of little cigar features on human exposure to tobacco smoke oxidants. In a balanced randomized cross-over study design in diverse smokers, subjects will be assigned to 6 exposure groups. These include a high oxidant unflavored little cigar exposure condition, a low oxidant unflavored little cigar exposure condition, a high oxidant flavored exposure condition, a low oxidant flavored exposure little cigar exposure condition, their usual cigarette, and a control condition (unlit little cigar). Following the smoking of each product, exhaled breath condensate samples will be collected at baseline (-15), 30, 60, 90, 120 and 150 minutes. Samples will be analyzed for levels of oxidant/inflammatory markers including hydrogen peroxide, 8-isoprostanes, and C-reactive protein, as well as nicotine, NNK and NNN. Aim 3. Determine the levels of biomarkers of potential harm in current users of little cigars relative to other tobacco products, including cigarettes and e-cigarettes in the Population and Tobacco Health Study (PATH). Aim 3a. Using Wave 1 and Wave 5 data, we will analyze and compare biomarkers of potential harm including oxidative stress (8-isoprostane) and inflammation (Soluble intercellular adhesion molecule-1, Interleukin 6). Secondary outcomes will include biomarkers of other tobacco smoke toxicants and nicotine metabolites, and behavioral measures of tobacco addiction. Aim 3b. Determine the effect of nitrate levels and rod length on biomarkers of potential harm.