Project 1: Translational Studies on Temperature and Solvent Effects on Electronic Cigarette-Derived Oxidants

项目1：温度和溶剂对电子烟氧化剂影响的转化研究

• 批准号: 10665896
• 负责人: JOHN P RICHIE
• 金额: $ 52.66万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665896
• 关键词: Acute; Address; Aerosols; Affect; Animal Model; Animals; Biological; Biological Markers; Blood; Characteristics; Chemicals; Cigarette; Cigarette Smoker; Crossover Design; Data; Development; Devices; Electronic cigarette; Epithelium; Exhalation; Exposure to; Flavoring; Free Radicals; Future; Health; Health Personnel; High temperature of physical object; Home; Human; In Vitro; Individual; Inflammation; Inhalation; Inhalation Exposure; Link; Liquid substance; Lung; Mainstreaming; Marketing; Measures; Mus; Nicotine; Normal Range; Nose; Oxidants; Oxidative Stress; Participant; Perception; Physical condensation; Policy Maker; Population Study; Production; Propylene Glycols; Pulmonary Inflammation; Randomized; Recommendation; Research; Research Personnel; Risk; Safety; Sampling; Site; Smoker; Solvents; Temperature; Testing; Tobacco smoke; Toxic effect; Toxicant exposure; Translating; Urine; Variant; Visit; addiction; animal data; biomarker development; biomarker validation; cold temperature; combustible cigarette; design; e-cigarette aerosols; electronic cigarette user; electronic liquid; in vivo; innovation; lipidomics; mouse model; novel; novel marker; oxidant stress; recruit; specific biomarkers; tobacco exposure; tobacco products; translational approach; translational study

Project Summary / Abstract: Project 1 Electronic cigarettes (EC) have gained increasing popularity due, in part, to the perception of them as a less harmful nicotine delivery device as compared to cigarettes. However, EC aerosols contain a number of harmful or potentially harmful constituents including free radicals and other oxidants that may impact the safety of EC. The diversity of products and rapidly evolving EC market poses a challenge for researchers seeking to understand the potential harms associated with their use, and for regulators who are asked to make determinations regarding their safety and seek data on device characteristics that impact EC harm. Our in vitro data show that EC temperature and e-liquid propylene glycol (PG) concentration are the major factors regulating the production of highly reactive free radicals and other oxidants. Further, our preliminary in vivo animal data suggest that these oxidants increase biomarkers of oxidative stress and inflammation. These data suggest the potential for harm in EC users and a potential link with specific EC design features. This proposed research provides valuable data for regulatory product standard development related to current and future ECs. It addresses our overall TCORS theme to better understand how the physical design and chemical constituents affect the toxicity and addictiveness of tobacco products with a focus on harm generated from oxidants. In Aim 1 we will conduct controlled animal exposure studies to determine the effects of temperature and PG concentration on biomarkers of exposure and harm, focusing on inflammation and oxidant stress. In Aim 2 we will conduct studies of current EC users, performing controlled inhalation exposure studies as well as naturalistic studies to determine the effects of EC temperature and e- liquid PG concentration on biomarkers of exposure and harm. We will use a randomized 4-treatment 4-period crossover design to compare low and high temperature and low and high PG e-liquid concentration. Acute effects including biomarkers of exposure, inflammation, oxidant stress and cardiorespiratory function will be measured before and immediately after rigidly controlled inhalation sessions, after a two-week period of naturalistic use and after on-site ad libitum use. In Aim 3 we will test for associations between solvent PG content and free radical production and biomarkers of exposure & harm in popular commercially available pod- type EC devices. Given the popularity of these devices, it is critical that the impact of important design features on free radical production and oxidative stress-related biomarkers in individuals using these products be investigated. Overall, this project addresses the well-established need for research regarding how variation in EC product design characteristics impact constituent exposure and toxicity and development of biomarkers to assess EC-related exposure and related harm or toxicity. As such, this research directly addresses the Toxicity domain of the TCORS 3.0 RFA.

项目概要/摘要：项目1 电子香烟（EC）已经获得越来越多的普及，部分原因是将它们视为一种电子烟。 与香烟相比，尼古丁输送装置的危害更小。然而，EC气溶胶含有一些 有害或潜在有害的成分，包括自由基和其他氧化剂， EC的安全性。产品的多样性和快速发展的电子商务市场对 寻求了解与其使用相关的潜在危害的研究人员，以及 被要求就其安全性做出决定，并寻求有关器械特征的数据， 影响EC危害。我们的体外数据表明，EC温度和电子液体丙二醇（PG） 浓度是调节高活性自由基和其他 氧化剂此外，我们初步的体内动物数据表明，这些氧化剂增加了生物标志物， 氧化应激和炎症。这些数据表明，EC使用者可能会受到伤害， 与特定EC设计功能相关联。这项研究为监管提供了有价值的数据。 与当前和未来EC相关的产品标准开发。它涉及我们的整体TCORS主题 为了更好地了解物理设计和化学成分如何影响毒性， 烟草制品的成瘾性，重点是氧化剂产生的危害。在目标1中， 进行受控动物暴露研究，以确定温度和PG的影响 集中在暴露和伤害的生物标志物，重点是炎症和氧化应激。在Aim中 2我们将对目前的EC使用者进行研究，并进行受控吸入暴露研究。 作为自然研究，以确定EC温度和电子液体PG浓度对 暴露和伤害的生物标志物。我们将使用随机化4治疗4阶段交叉设计， 比较低温和高温以及低PG电子液体浓度和高PG电子液体浓度。急性影响包括 将测量暴露、炎症、氧化应激和心肺功能的生物标志物 在严格控制的吸入治疗之前和之后，经过两周的自然主义治疗 使用和现场随意使用后。在目标3中，我们将测试溶剂PG含量之间的关联 和自由基的生产和生物标志物的暴露和伤害，在流行的市售豆荚， EC型装置。鉴于这些设备的普及，重要设计的影响至关重要。 使用这些药物的个体中自由基产生和氧化应激相关生物标志物的特征 产品进行调查。总的来说，这个项目解决了已经确立的研究需求， 关于EC产品设计特征的变化如何影响成分暴露和毒性 以及开发生物标志物以评估EC相关暴露和相关危害或毒性。因此，在本发明的一个方面， 本研究直接针对TCORS 3.0 RFA的毒性领域。