Dose-Dependent Health Impacts of Flavorings in E-cigarette Liquids Assessed via Sensory Irritation in the Mouse Airway

通过小鼠气道的感觉刺激评估电子烟液体中调味剂对健康的剂量依赖性影响

• 批准号: 10064412
• 负责人: WEIHONG LIN
• 金额: $ 14.21万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10064412
• 关键词: Acetic Acids; Behavior; Benzoates; Calcitonin Gene-Related Peptide; Capsaicin; Centers for Disease Control and Prevention (U.S.); Chemical Exposure; Chemical Stimulation; Chemicals; Chronic; Conditioned Reflex; Coughing; Data; Dose; Dyspnea; Edema; Electronic cigarette; Electrophysiology (science); Event-Related Potentials; Fatigue; Flavoring; Funding; Health; Hypersensitivity; Inflammation; Irritants; Knowledge; Lung; Masks; Measurement; Measures; Mechanical Stimulation; Mediating; Monitor; Mucous Membrane; Mucous body substance; Mus; National Institute of Drug Abuse; Nerve; Nerve Fibers; Neuropeptides; Nicotine; Nociception; Nose; Occupational; Parents; Patients; Physiological; Policies; Positioning Attribute; Reflex action; Regulation; Research; Respiration; Respiratory Mucosa; Risk; Risk Assessment; Sales; Sensory; Shortness of Breath; Speed; Stimulus; Structure of mucous membrane of nose; Structure of respiratory epithelium; Substance P; Symptoms; Testing; Tetrahydrocannabinol; Time; Trachea; Tracheal Epithelium; Vasodilation; Vitamin E Acetate; afferent nerve; airway hyperresponsiveness; airway inflammation; base; e-cigarette aerosols; electronic cigarette use; electronic liquid; epithelial injury; in vivo; innovation; insight; irritation; liquid nicotine; marijuana use; nerve supply; neuronal circuitry; news; novel strategies; parent grant; respiratory; respiratory health; response; toxicant; vanillin; vaping; vaping associated lung injury; vapor

Abstract The abuse use of electronic cigarette (e-cig) or vaping is a worldwide health problem. Major symptoms of e-cig, or vaping, product use-associated lung injury (EVALI) include cough and shortness of breath. In general, sensory irritation induced by chemical or mechanical stimulation in the lower airway, such as trachea triggers reflexive cough and dyspnea. However, we lack a direct assessment of sensory activation induced by e-cig constituents, tetrahydrocannabinol (THC) and vitamin E acetate that potentially cause EVALI. Furthermore, there is a lack of research data whether chronic vaping neurogenically hyper-sensitizes the airway. In our parent grant project, we electrophysiologically record event-related potentials (ERP) in the nasal mucosa to objectively assess sensory irritation evoked by e-cig flavorings, nicotine, PG/VG and flavored popular e-liquids. Our data have demonstrated dose-dependent sensory activation evoked by these e-liquid constituents. We hypothesize that certain e-liquid constituents cause sensory irritation in the trachea, which subsequently triggers reflexive cough and dyspnea, and that long-term e-cig vapor exposure hyper-sensitizes the airway mucosa. We will test our hypotheses by pursuing research: 1) measuring ERP from mouse tracheal mucosa to evaluate sensory irritation caused by e-liquid constituents, THC and vitamin E acetate, 2) monitor and correlate tracheal mucosal sensory irritation with respiratory alteration, and 3) determining whether 2-week vapor exposure sensitizes the tracheal mucosa resulting in potentiated responses to e-liquid constituents and tussive stimuli. We have accumulated sufficient data from our parent grant project that will enable us to speed up this proposed research substantially by narrowing the tested stimulus concentration ranges. Importantly, we have successfully measured in vivo ERP responses to some e-liquid flavorings, nicotine, and tussigenic capsaicin, and acetic acid from tracheal epithelium that has intact nerve innervation. This direct recording from trachea mucosa presents an innovative approach for the risk assessment of e-cig vaping. Together, our preliminary data promise for time-sensitive, significant results towards a better understanding of the health effects of e-cig vaping and causal factors of EVALI and help guide FDA regulation of e-cig manufacture and sale.

抽象的 滥用电子烟（E-CIG）或VAPING是全球健康问题。电子烟的主要症状， 或蒸发，产品使用相关的肺损伤（评估）包括咳嗽和呼吸急促。一般来说， 下气道中的化学或机械刺激引起的感觉刺激，例如气管触发器 反射性咳嗽和呼吸困难。但是，我们缺乏对电子烟引起的感觉激活的直接评估 成分，四氢大麻酚（THC）和维生素E醋酸盐可能会引起评估。此外， 缺乏研究数据是否会在神经源上过度敏感性气道。在我们的 父母赠款项目，我们在鼻粘膜中电生理记录与事件相关的电位（ERP） 客观地评估E-CIG调味剂，尼古丁，PG/VG和风味流行的电子液体引起的感觉刺激。 我们的数据证明了这些电子液体成分引起的剂量依赖性感觉激活。我们 假设某些电子液体成分引起气管的感觉刺激，随后 触发反射性咳嗽和呼吸困难，长期的电子烟蒸气暴露使气道超敏 粘膜。我们将通过进行研究来检验我们的假设：1）测量小鼠气管粘膜的ERP 评估由电子液体成分引起的感觉刺激，THC和维生素E乙酸，2）监测并相关 气管粘膜感觉刺激随呼吸道改变而刺激，3）确定2周蒸气是否是否 暴露使气管粘膜敏感，导致对电子液体成分的反应增强 刺激。我们从父母赠款项目中积累了足够的数据，这将使我们能够加快这一点 通过缩小测试的刺激浓度范围，提出的研究很大程度上。重要的是，我们有 成功地测量了对某些电子液体调味剂，尼古丁和杜塞尼辣椒素的体内ERP反应， 来自气管上皮的乙酸，具有完整的神经支配。该直接录音来自气管 Mucosa提出了一种创新的方法，用于评估电子烟烟的风险。在一起，我们的初步 对时间敏感，重大结果的数据承诺，以更好地理解电子烟的健康影响 评估的蒸发和因素因素，并有助于指导FDA对电子烟制造和销售的调节。