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 监管科学的烟草中心认可了7种研究重点，其中2个重要 领域是毒性和健康后果 烟草产品和结束。 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） 小鼠作为结构的假设是长期吸入（3-MO） A/J小鼠到E-cig气溶胶会诱导肺动脉血管的变化 引起肺动脉高压，这些变化会因调味剂引起的炎症而产生和/或加剧。 此外，可以比较这种电子烟引起的心血管毒物和单个调味剂的毒性 根据不良变化的范围（3.5周年）通过吸入将 （4-MO的）到包含丙二醇，尼古丁和 没有调味料； Schnapps）基于人类用法和公开的拨件。 支撑：1a）确定两性青少年小鼠的长期（3-mo。）吸入暴露于 E-cig气溶胶（有或没有调味剂）会产生结构，形态学和 /或分子重塑 肺血管含量。 使用以前在该实验室开发的范式的范式进行改动，用于订购无烟烟草产品； 1b）使用SA1A中暴露的相同小鼠研究非末端的时间过程 与肺动脉高压和/或血清的发展相关的系统变化 在E -CIG暴露期间-30，-60，-90天的血管损伤和促炎细胞因子的标记 确定3-MO暴露于同一持续的E-CIG气溶胶90天 肺动脉高压和心肺/炎症结果在目标1a和1b中测得。 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，向公众教育与使用风味的电子烟有关的健康 展示如何使用味道的电子烟如何导致威胁生命的健康，这可能导致禁止您 这些创新研究的特定调味料/类型的电子烟。 公共卫生查询：E-CIG使用，例如长期吸烟，可能诱发心肺/炎症 作用，包括可能导致pH的肺的血管变化 研究确定。 法规。 迄今为止，关于毒和健康，阻碍了新法规的启动。