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.

摘要 滥用电子烟（e-cig）或vaping是一个全球性的健康问题。电子烟的主要症状， 或vaping，产品使用相关的肺损伤（EVALI）包括咳嗽和呼吸急促。总的来说， 下呼吸道化学或机械刺激引起的感觉刺激，如气管触发 反射性咳嗽和呼吸困难。然而，我们缺乏对电子烟引起的感觉激活的直接评估 四氢大麻酚（THC）和维生素E醋酸酯可能导致EVALI。此外，委员会认为， 缺乏长期吸电子烟是否神经性地使气道超敏的研究数据。在我们 在家长资助项目中，我们通过电生理记录鼻粘膜的事件相关电位（ERP）， 客观地评估由电子烟调味剂、尼古丁、PG/VG和调味的流行电子液体引起的感官刺激。 我们的数据已经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中的感觉刺激，其随后 引发反射性咳嗽和呼吸困难，长期暴露于电子烟蒸汽会使气道过敏 粘膜我们将通过以下研究来验证我们的假设：1）测量小鼠气管粘膜的ERP， 评估电子烟液成分、四氢大麻酚和维生素E醋酸酯引起的感官刺激，2）监测并关联 气管粘膜感觉刺激伴呼吸改变，以及3）确定2周蒸汽 暴露使气管粘膜敏感，导致对电子液体成分和咳嗽的增强反应。 刺激。我们已经积累了足够的数据，从我们的父母赠款项目，将使我们能够加快这一点 建议通过大幅缩小测试的刺激浓度范围来进行研究。重要的是我们有 成功测量了对一些电子液体调味剂、尼古丁和致咳嗽辣椒素的体内ERP反应， 和乙酸从具有完整神经支配的气管上皮中提取。这段来自气管的直接录音 Mucosa为电子烟的风险评估提供了一种创新方法。我们初步的 数据承诺为更好地了解电子烟对健康的影响提供时间敏感的重要结果 电子烟和EVALI的因果因素，并帮助指导FDA对电子烟制造和销售的监管。