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)或电子烟是一个全球性的健康问题。电子烟的主要症状， 或蒸发，产品使用相关的肺损伤(EVALI)包括咳嗽和呼吸急促。总体而言, 由下呼吸道的化学或机械刺激引起的感官刺激，如触发气管 反射性咳嗽和呼吸困难。然而，我们缺乏对e-cig引起的感官激活的直接评估。 四氢大麻酚(THC)和维生素E醋酸酯可能导致EVALI的成分。此外， 目前还缺乏研究数据表明，慢性蒸发是否会导致呼吸道过度敏感。在我们的 家长资助计划，我们记录事件相关电位(事件相关电位)在鼻粘膜，以 客观地评估电子烟调味品、尼古丁、PG/VG和风味流行的电子液体引起的感官刺激。 我们的数据表明，这些电子液体成分引起的感觉激活具有剂量依赖性。我们 假设某些电子液体成分会引起气管的感官刺激，从而 引发反射性咳嗽和呼吸困难，长期接触电子烟蒸气会使呼吸道高度敏感 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 评估电子液体成分、THC和维生素E醋酸酯对感官刺激的影响，2)监测和关联 有呼吸改变的气管粘膜感觉刺激，以及3)确定2周的蒸气 暴露使气管粘膜敏感，导致对电子液体成分和咳嗽药的反应增强。 刺激物。我们已经从我们的母基金项目中积累了足够的数据，这将使我们能够加快这一进程 建议的研究主要是通过缩小测试的刺激浓度范围进行的。重要的是，我们有 成功测量了体内事件相关电位对一些电子液体调味品、尼古丁和辣椒素的反应， 以及来自具有完整神经支配的气管上皮的醋酸。从气管直接记录 粘膜为电子烟蒸发的风险评估提供了一种创新的方法。一起，我们的初选 数据有望为更好地理解电子烟对健康的影响提供具有时间敏感性的重要结果 蒸发和EVALI的因果因素，并有助于指导FDA对电子烟生产和销售的监管。