Electronic cigarette cardiotoxicity varies by flavorings: What can we learn from mice?

电子烟的心脏毒性因香料而异：我们可以从老鼠身上学到什么？

• 批准号: 10219729
• 负责人: Gabriele Grunig
• 金额: $ 21.19万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219729
• 关键词: A/J Mouse; Adolescence; Adolescent; Adult; Adverse effects; Aerosols; Age; Americas; Apple; Area; Belief; Blood Vessels; Brain; Cardiopulmonary; Cardiotoxicity; Cardiovascular system; Categories; Cessation of life; Chronic; Cigarette; Cinnamon - dietary; Climacteric; Communication; Data; Development; Devices; Diacetyl; Disease; Education; Electronic Nicotine Delivery Systems; Electronic cigarette; Emerging Tobacco Products; Exposure to; Family Smoking Prevention and Tobacco Control Act; Female; Flavoring; Genus Vanilla; Glycerol; Health; High School Student; Hospitalization; Human; Individual; Inflammation; Inflammatory; Inflammatory Response; Ingestion; Inhalation; Inhalation Exposure; Knowledge; Label; Laboratories; Lead; Learning; Life; Liquid substance; Lung; Marketing; Measurable; Measures; Menthol; Molecular; Morphology; Mouse Strains; Mus; Nicotine; Outcome; Outcome Measure; Peach; Plasma; Poison; Policies; Propylene Glycols; Public Health; Publishing; Pulmonary Emphysema; Pulmonary Heart Disease; Pulmonary Hypertension; Regulation; Research; Research Priority; Risk; Sales; Science; Serum Markers; Smokeless Tobacco; Smoking Behavior; Structure; System; Testing; Time; Tobacco; Tobacco smoking behavior; Tobacco use; Toxic effect; Translating; Vaporizer; Youth; addiction; aerosolized; base; cardiovascular health; cigarette smoke-induced; cigarette smoking; comparative; cytokine; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; electronic liquid; hookah; innovation; junior high school; male; nicotine exposure; public education; sex; tobacco products; vaping; vascular injury; water vapor; young adult

Abstract Tobacco Center of Regulatory Science recognizes 7 categories of research priorities, of which 2 important domains are toxicity and health consequences, with emphasis on cardiopulmonary impacts of new and emerging tobacco products and ENDS. The proposed study informs the FDA in regulations regarding the comparative toxicity of e-cigarette (e-cig) flavorings using cardiovascular health, particularly pulmonary hypertension (PH) in mice as an outcome. The over-arching hypothesis is that long-term inhalation exposure (3-mo) of adolescent A/J mice to e-cig aerosols induce changes in pulmonary vasculature predisposing adult male and female mice to pulmonary hypertension, and these changes arise and/or exacerbated by flavoring-induced inflammation. Moreover, that e-cig-induced cardiovascular toxicity can be compared and the toxicity of individual flavorings graded based on the extent of adverse change. Mice (3.5-wk-of-age) will be exposed by inhalation into adulthood (4-mo-of-age) to e-cig aerosols from a self-made tank system containing propylene glycol, glycerin, nicotine and with and without flavoring; selection of flavors (vanilla, cinnamon, menthol, double apple hookah and peach schnapps) are based on human usage and published diacetyl levels. A single aim (with multiple sub-aims) is proposed: 1A) to determine whether long-term (3-mo.) inhalation exposure of adolescent mice of both sexes to e-cig aerosols (with or without flavorings) produces structural, morphological and/or molecular remodeling of the pulmonary vasculature. The toxicity of e-cig flavorings will be classified based on extent of cardiopulmonary alterations using a paradigm previously developed in this laboratory for ordering smokeless tobacco products; 1B) using the same mice exposed in SA1A to investigate the time course of effects by examining non-terminal systemic changes associated with the development of pulmonary hypertension and/or emphysema, e.g., serum markers of vascular injury and pro-inflammatory cytokines on days -30, -60, -90 during e-cig exposure; 1C) to determine persistent effects of e-cig aerosols 90 days after cessation of the 3-mo exposure on the same pulmonary hypertension and cardiopulmonary/inflammatory outcomes measured in aims 1A and 1B. Results of these studies will empower the FDA to promulgate more explicit warning labels on e-cig packaging that could, in turn, educate the public on health risks associated with use of flavored e-cigs. Moreover, unequivocal demonstration of how flavored e-cig use could lead to life-threatening health issues could result in banning the sale of specific flavorings/types of e-cigarettes. These innovative studies introduce a new and understudied public health query: e-cig use, like long-term cigarette smoking, can induce cardiopulmonary/inflammatory effects, including vascular changes in the lungs that can lead to PH, an understudied area of cardiovascular research. Identifying a relationship between vaping and PH has critical implications for setting policies/imposing regulations. These studies that assess cardiopulmonary implications of “vaping” can begin to fill knowledge gaps on toxicity and health that to date impede the launch of new regulations.

抽象的 监管科学中心烟草中心认可了7种研究重点，其中2个重要 领域是毒性和健康后果，重点是新兴和新兴的心肺影响 烟草产品和目的。拟议的研究向FDA提供了有关比较的法规 使用心血管健康的电子烟（E-CIG）调味剂的毒性，尤其是肺动脉高压（pH） 小鼠作为结果。章节过度的假设是青少年的长期吸入暴露（3-MO） A/J小鼠到E-cig气溶胶会诱导肺动脉炎的变化 肺动脉高压，这些变化会因调味剂引起的注射而产生和/或加剧。 此外，可以比较E-CIG诱导的心血管毒性，并具有单个口味的毒性 根据不良变化的程度进行分级。小鼠（3.5周的年龄）将通过吸入成年暴露 （4-MO时代）到包含丙二醇，甘油，尼古丁和 带有和不调味；选择口味（香草，肉桂，薄荷醇，双苹果水烟和桃子 schnapps）基于人类使用和已发表的二乙酰水平。一个目标（具有多个子iams）是 提议：1a）确定是否长期（3-mo。）吸入两性的青少年小鼠 E-cig气溶胶（有或没有调味剂）会产生结构，形态和/或分子重塑 肺脉管系统。 E-CIG口味的毒性将根据心肺的范围进行分类 使用以前在该实验室开发的范式来订购无烟烟草产品的范例的变化； 1b）使用SA1A中暴露的相同小鼠通过检查非末端来研究时间过程 与肺动脉高压和/或肺气肿的发展相关的系统性变化，例如 在电子烟暴露期间-30，-60，-90天血管损伤和促炎细胞因子的标记； 1C）至 确定3-MO暴露于同一的3-MO暴露后90天的E-CIG气溶胶的持续作用 AIMS 1A和1B中测得的肺动脉高压和心肺/炎症结果。结果 这些研究将使FDA能够在E-CIG包装上颁布更多明确的警告标签，该警告标签可以 反过来，向公众教育与使用调味电子烟有关的健康风险。而且，明确 演示如何使用调味的电子烟可能会导致威胁生命的健康问题，这可能导致禁止 销售特定的调味料/类型的电子烟。这些创新的研究介绍了一个新的知识 公共卫生查询：E-CIG使用，例如长期吸烟，可能引起心肺/炎症性 作用，包括肺部的血管变化，可能导致pH，这是心血管的理解区域 研究。确定烟与pH之间的关系对制定政策/施加至关重要 法规。这些评估“烟”心肺影响的研究可以开始填补知识差距 关于迄今为止的毒性和健康，阻碍了新法规的启动。