Cardiopulmonary outcomes of dual cigarette and e-cigarette use in animal models of chronic exposure

慢性暴露动物模型中同时使用香烟和电子烟的心肺结果

• 批准号: 10666054
• 负责人: Chiara Bellini
• 金额: $ 75.51万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-18 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666054
• 关键词: Acetylcholine; Adult; Aerosols; Affect; Air; Airway Resistance; American; Animal Model; Animals; Aorta; Apolipoprotein E; Area; Arterial Fatty Streak; Biological Availability; Blood; Bronchial Provocation Tests; C57BL/6 Mouse; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Categories; Cessation of life; Chemicals; Chronic; Cigarette; Cigarette Smoker; Clinical; Collagen; Cotinine; Data; Deposition; Devices; Drug Kinetics; EFRAC; Elastic Fiber; Elasticity; Electronic cigarette; Evaluation; Exposure to; FDA approved; Family Smoking Prevention and Tobacco Control Act; Generations; Health; Health Care Costs; Heart; Heterogeneity; Inhalation; JUUL; Knowledge; Left ventricular structure; Lung; Magnetic Resonance Imaging; Measures; Mechanics; Modeling; Mus; Nebulizer; Nicotine; Nose; Outcome; Oxygen; Property; Proxy; Pulmonary Heart Disease; Regulation; Relaxation; Reporting; Research; Resistance; Respiratory System; Risk; Risk Factors; Safety; Salts; Shortening Fraction; Smoke; Smoker; Smoking; Sodium Chloride; Solvents; Source; Structure; System; Testing; Tissues; Tobacco; Virginia; Wild Type Mouse; Workload; Youth; abdominal aorta; absorption; aerosolized; base; cardiovascular risk factor; cigarette smoke; combustible cigarette; comorbidity; design; electronic cigarette use; epidemiologic data; experience; experimental study; exposure to cigarette smoke; hypercholesterolemia; interest; irritation; mechanical properties; methacholine; mouse model; nicotine craving; nicotine vapor; pressure; respiratory; response; smoke inhalation; smoking cessation; smoking-related disease; tobacco flavor; tobacco products; translational potential; vaping

PROJECT SUMMARY New generation pod-style nicotine salt e-cigarettes (e-cigspod) are popular because of their sleek design and ability to deliver nicotine levels similar to those of conventional tobacco cigarettes (cigs). Nicotine salts are easier to inhale than the free-base form of nicotine found in previous generation e-cigs. While the long-term health impact of cig smoke is well known, the consequences of chronic e-cig use remain in question, and data is needed to justify immediate FDA regulations. A substantial portion of smokers are unsuccessful in using e-cigs to support their cessation efforts and instead become dual users. The chemical profile of cig smoke and e-cigpod aerosols is different, which suggests that the health effects of chronic smoking and vaping may not fully overlap. Building upon this, we hypothesize that cig smoking and e-cigpod vaping, are independent risk factors for cardiopulmonary disease, whose superposition exacerbates the maladaptive remodeling of the lungs, heart, and vasculature compared to either practice alone. To test this hypothesis, we will expose hypercholesterolemic and wildtype mice to nebulized nicotine, aerosolized solvent carrier, e-cigpod aerosols, and cig smoke (naïve mice), or a combination of the two (both naïve and previously cig smoke-exposed mice) and we will compare the structural and functional remodeling of the cardiovascular and respiratory systems. We will generate e-cigpod aerosols from pods in Tobacco flavor at 5% nicotine strength. Motivated by the idea that smokers who use e-cigs as cessation aids may vape until they satisfy their nicotine cravings, we will perform experiments to achieve equal cotinine bioavailability in the mouse blood, while maintaining the same daily duration of exposure. We will measure the mechanical properties of the of aorta (tissue stiffness, distensibility, and elastic storage), heart (fractional shortening and ejection fractions), and lungs (resistance and elastance). We will characterize tissue microstructure (air space sizes, collagen content, and elastic fiber integrity) to highlight the factors that most contribute to the observed functional changes. Knowledge gained from this project will provide scientific evidence in support of data-driven e-cig regulation under The Family Smoking Prevention and Tobacco Control Act (FSPTCA), specifically concerning the health risks of dual combustible and electronic cigarette use.

项目摘要 新一代豆荚式尼古丁盐电子烟（e-cigspod）因其时尚的设计和 能够提供与传统烟草香烟（CIG）相似的尼古丁水平。尼古丁盐更容易 比上一代电子烟中的游离碱形式的尼古丁更容易吸入。虽然长期健康 吸烟的影响是众所周知的，长期使用电子烟的后果仍然存在问题，需要数据 来证明食品和药物管理局的规定是正确的很大一部分吸烟者不成功地使用电子烟来支持 他们停止努力，反而成为双重用户。cig烟雾和e-cigpod气溶胶的化学特征 是不同的，这表明长期吸烟和吸电子烟对健康的影响可能并不完全重叠。建筑 基于此，我们假设吸烟和电子烟是心肺功能障碍的独立危险因素。 疾病，其叠加加剧了肺，心脏和血管的适应不良重塑 与单独的实践相比。为了验证这一假设，我们将高胆固醇血症和野生型 小鼠吸入雾化尼古丁、雾化溶剂载体、e-cigpod气雾剂和cig烟雾（未处理小鼠），或 这两个组合（幼稚和先前cig烟雾暴露的小鼠），我们将比较结构 以及心血管和呼吸系统的功能重塑。我们将产生电子烟烟雾， 烟用香精中的豆荚，尼古丁浓度为5%。动机是吸烟者使用电子烟戒烟的想法 艾滋病可能vape，直到他们满足他们的尼古丁渴望，我们将进行实验，以实现平等的可替宁 在小鼠血液中的生物利用度，同时保持相同的每日暴露持续时间。我们将测量 主动脉的机械特性（组织硬度、可扩张性和弹性储存）、心脏的机械特性（分数 缩短和射血分数）和肺（阻力和弹性）。我们将描述组织的特征 微观结构（空气空间大小，胶原蛋白含量和弹性纤维完整性），以突出最重要的因素 有助于观察到的功能变化。从这个项目中获得的知识将提供科学证据 根据《家庭吸烟预防和烟草控制法》，支持数据驱动的电子烟监管 （FSPTCA），特别是关于使用双重可燃物和电子烟的健康风险。