Project 1: Effects of unventilated filters on pattern of cigarette use, toxicant exposure and uptake of alternative nicotine products

摘要 2014年卫生局局长的报告指出，有提示性证据表明， 过滤器在肺腺癌发病率增加中起作用。在最近的一个重量， 我们对证据进行了审查，包括对生物相容性的深入分析，我们得出结论， 高度提示性的证据表明，过滤器通气反而增加了肺腺癌的风险， 其他肺癌随着吸烟率的下降而下降。这种风险的增加是基于如何 通风改变了香烟燃烧的方式和香烟的弹性， 尼古丁和有害的烟雾成分到肺的外周部分，其中腺癌更多 通常发生。一个强有力的理由可以让FDA考虑规范过滤器通风，包括 禁止，基于腺癌发病率的增加，加强有毒物质暴露，误解 关于这些香烟的相对安全性以及由于香烟的 弹性然而，迄今为止，还没有关于去除过滤器通风对吸烟的影响的研究 行为和由此产生的接触和毒性。因此，本项目的主要目标是评估这一点， 重要的是，这样做的背景下，实验市场，允许和不允许访问， 替代的尼古丁递送系统（ANDS;例如，电子烟、无烟烟草和尼古丁替代品 治疗）。次要目标包括研究暴露的预测因素以及暴露的类型和特征。 是被选中的。研究设计为2 × 2，其中吸烟者将被随机化（4个组中，每个组N=125）。 最终N=400的条件和20%的脱落率）对通风或不通风香烟，有和没有 进入ANDS。经验证的暴露和新的生物标志物（例如，代谢组学和基因表达） 将在研究过程中分析尿液、血液和肺中采集的样本。吸烟行为将是 通过抽吸地形和吸入进行评估。我们假设使用不通风香烟的受试者将 经验：1）吸烟较少; 2）毒物暴露和影响较少; 3）吸烟强度较低， 吸入深度;和4）戒烟天数增加，观察到的效果更大 在那些有机会获得ANDS的吸烟者中。此外，吸烟和接触的预测因素 生物标志物将取决于香烟类型，获得ANDS，消费者的看法和对 吸烟、人口统计学和吸烟史变量。选择的产品类型可能是电子烟 尼古丁含量更高的口味这个项目是创新的，因为它是第一个探索 不通气与通气香烟对广泛生物标志物的影响，包括靶向 特别是在具有ANDS的市场背景下。它的重要性在于它将提供 FDA关于香烟过滤器通风是否可能产生任何意外后果的信息 被淘汰了

ABSTRACT The 2014 Surgeon General's report indicated that there was suggestive evidence demonstrating that ventilated filters have played a role in the increased incidence of lung adenocarcinoma. In a more recent weight of evidence review by us, including an in-depth analysis of biological plausibility, we concluded that there was highly suggestive evidence that filter ventilation paradoxically increased the risk of lung adenocarcinoma, while other lung cancers decreased with decreasing smoking prevalence. This increase in risk is based on how ventilation alters the way the cigarette burns and the elasticity of the cigarette that allows greater delivery of nicotine and harmful smoke constituents to the peripheral parts of the lung, where adenocarcinomas more commonly occur. A strong case can be made for the FDA to consider regulating filter ventilation, including a ban, based on the increasing incidence of adenocarcinoma, enhanced toxicant exposures, misperceptions about the relative safety of these cigarettes and increased abuse liability resulting from the cigarette's elasticity. However, to date, there are no studies on the impact of removing filter ventilation on smoking behavior and resultant exposures and toxicity. Therefore, the primary goal of this project is to assess this, and importantly to do so in the context of an experimental marketplace that allows and does not allow access to alternative nicotine delivery systems (ANDS; e.g., e-cigarettes, smokeless tobacco and nicotine replacement therapy). Secondary aims include studying the predictors of exposure and the type and characteristics of ANDS that are chosen. The study design is a 2 x 2, in which smokers will be randomized (N=125 in each of 4 conditions and 20% dropout rate for final N=400) to ventilated or unventilated cigarettes, with and without access to ANDS. Both validated exposure and novel biomarkers (e.g., metabolomics and gene expression) collected in urine, blood, and lung will be analyzed during the course of the study. Smoking behavior will be assessed by puff topography and inhalation. We hypothesize that subjects using unventilated cigarettes will experience: 1) fewer cigarettes smoked; 2) less toxicant exposure and effect; 3) less smoking intensity and depth of inhalation; and 4) greater number of days abstinent from cigarettes, with greater effects observed among those smokers with access to ANDS. Furthermore, the predictors of cigarette use and exposure biomarkers will be dependent on cigarette type, access to ANDS, consumer perceptions and response to the cigarettes, demographic and smoking history variables. The type of product chosen will likely be e-cigarettes with higher nicotine doses and that are flavored. This project is innovative because it is the first to explore the effects of unventilated vs. ventilated cigarettes on a broad range of biomarkers, including ones that target the lung specifically, and within the context of a marketplace with ANDS. It is significant because it will provide the FDA information on whether or not there might be any unintended consequences if cigarette filter ventilation was eliminated.