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

项目 1：不通风滤嘴对卷烟使用模式、毒物暴露和替代尼古丁产品吸收的影响

• 批准号: 10246919
• 负责人: DOROTHY K HATSUKAMI
• 金额: $ 48.21万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246919
• 关键词: Adenocarcinoma; Affect; Age; Air; Alternative Nicotine Delivery Systems; Aromatic Polycyclic Hydrocarbons; Biological; Biological Markers; Blood; Bronchoscopy; Burn injury; Carcinogens; Characteristics; Cigarette; Cigarette Smoker; Clinical Trials; Complement; DNA Adducts; Dependence; Dose; Dropout; Elasticity; Electronic cigarette; Environment; Ethnic group; Evaluation; Excision; Exposure to; Fibrinogen; Fostering; Future; Gene Expression; Goals; Health; Incidence; Inflammation; Inhalation; Inhalation Exposure; Intake; Lung; Lung Adenocarcinoma; Malignant neoplasm of lung; Methods; Monitor; Mutagens; Nicotine; Nitrosamines; Outcome; Pattern; Perception; Peripheral; Play; Price; Randomized; Regulation; Reporting; Research; Research Design; Risk; Role; Safety; Severities; Smoke; Smokeless Tobacco; Smoker; Smoking; Smoking Behavior; Smoking History; Suggestion; Surgeon; Tars; Temperature; Time; Tobacco; Toxic effect; Toxicant exposure; Urine; Weight; base; cigarette smoke; cigarette smoking; combustible cigarette; design; experience; innovation; metabolomics; nicotine replacement; novel; novel marker; racial and ethnic; response; sex; smoking cessation; smoking prevalence; tobacco products; uptake; ventilation; voucher

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.

抽象的 2014年外科医生的报告表明，有暗示的证据表明通风 过滤器在肺腺癌的发病率增加中发挥了作用。在最近的重量 我们的证据审查，包括对生物合理性的深入分析，我们得出的结论是 极具启发性的证据表明，过滤通风矛盾地增加了肺腺癌的风险，而 其他肺癌随着吸烟率降低而减少。这种风险增加是基于如何 通风改变了香烟燃烧的方式和允许更多输送的香烟的弹性 肺部周围部分的尼古丁和有害烟雾成分，腺癌更多 通常发生。可以为FDA考虑考虑调节过滤通风的强烈案例，包括 禁止，基于腺癌的发病率不断增加，毒性暴露，误解 关于这些香烟的相对安全性以及增加了香烟造成的滥用责任 弹性。但是，迄今为止，尚无关于去除过滤通风对吸烟的影响的研究 行为和结果暴露和毒性。因此，该项目的主要目标是评估这一点，并 重要的是在实验市场的背景下这样做，该市场允许并且不允许访问 替代性尼古丁输送系统（和例如电子烟，无烟烟草和尼古丁替代品 治疗）。次要目的包括研究暴露的预测因素以及 和选择的。研究设计是2 x 2，其中吸烟者将被随机化（4个中的n = 125 条件和最终n = 400的辍学率为20％），用于通风或未发泄的香烟，有和没有 访问和。曾经验证的暴露和新型生物标志物（例如代谢组学和基因表达） 在研究过程中，将分析尿液，血液和肺部的收集。吸烟行为将是 通过泡芙地形和吸入评估。我们假设使用无通烟的受试者将 经验：1）抽烟较少； 2）毒物的暴露和影响较小； 3）更少的吸烟强度和 吸气深度； 4）戒烟的天数更大，观察到更大的影响 在那些吸烟者中，可以使用和使用。此外，香烟使用和暴露的预测因素 生物标志物将取决于香烟类型，访问和对消费者的看法以及对 香烟，人口统计学和吸烟史变量。选择的产品类型可能是电子烟 具有较高的尼古丁剂量，并具有调味剂。该项目具有创新性，因为它是第一个探索 未通风与通风卷烟对广泛的生物标志物的影响，包括针对的生物标志物 特别是在带有AND的市场的背景下进行肺。这很重要，因为它将提供 FDA信息有关是否会产生任何意外后果，如果香烟过滤通风会产生任何意外后果 被淘汰。