Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study

电子烟的通气和肺内皮毒性 (VaPE-Tox)：随机交叉试点研究

• 批准号: 9130400
• 负责人: Elizabeth Oelsner
• 金额: $ 12万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9130400
• 关键词: Acrolein; Acute; Affect; Airway Resistance; Albuterol; Angiography; Apoptosis; Asthma; Blood Vessels; Blood flow; Breathing; Bronchoconstriction; Bronchodilator Agents; C Fiber; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Cigarette; Communication; Crossover Design; Data; Defect; Development; Electronic cigarette; Endothelium; Environmental air flow; Epithelium; Exhalation; Flavoring; Functional disorder; Funding; Gadolinium; General Population; Gold; Health; Heating; Helium; Hospitalization; Human; Image; In Vitro; Inflammation; Irritants; Label; Liquid substance; Lung; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Measures; Mucous body substance; Mus; Neuropeptides; Nicotine; Nitric Oxide; Oscillometry; Pathogenesis; Perfusion; Peripheral; Persons; Physiological; Pilot Projects; Production; Propylene Glycols; Public Health; Public Health Education; Pulmonary Emphysema; Pulmonary Ventilation; Radiation; Randomized; Regulation; Research; Respiratory physiology; Risk; Safety; Sampling; Site; Spirometry; Testing; Toxic effect; Toxicology; Vasodilator Agents; Work; acute toxicity; airway hyperresponsiveness; airway inflammation; airway remodeling; asthmatic; effective therapy; electric impedance; endothelial dysfunction; experience; gadolinium oxide; innovation; lung imaging; methacholine; non-invasive imaging; public education; toxicant; vapor; young adult

 DESCRIPTION (provided by applicant): Determination of the acute pulmonary toxicities of e-cigarettes in young adults is of major public health importance. E-cigarette vapor contains established toxicants which may be anticipated to cause acute damage to the airways and the pulmonary microvasculature resulting in the eventual development of chronic lung disease, for which there remain few effective therapies. Magnetic resonance imaging (MRI) and angiography (MRA) measures are promising approaches to detecting and characterizing the anticipated acute pulmonary toxicities of e-cigarettes. Hyperpolarized helium (3He)-enhanced MRI may be more sensitive than spirometry, a global lung function measure, for determination of airway toxicities. 3He-enhanced MRI has been used to demonstrate the extent of ventilation defects in healthy persons with normal spirometry; to measure ventilation changes in asthmatics pre- and post-challenge with bronchodilators and methacholine; and to predict pulmonary hospitalizations in persons with COPD. Meanwhile, until recently, non-invasive measures of pulmonary vascular toxicities were lacking. Our group developed an innovative measure of pulmonary microvascular blood flow on gadolinium (Gd)-enhanced MRA, which we found to be markedly abnormal in early chronic obstructive pulmonary disease (COPD) and emphysema, and to be associated with increased endothelial microparticles, a marker of endothelial dysfunction. Nonetheless, neither of these sensitive, non-invasive, repeatable, and reproducible measures has ever been used to assess e-cigarette toxicities. We therefore propose a pilot study using a gold-standard randomized crossover design to test the acute effects of a standardized e-cigarette exposure on 3He-enhanced MRI and Gd-enhanced MRA in ten healthy, young adult e-cigarette users. We hypothesize that e-cigarette vapor inhalation will result in an acute increase in global and regional ventilation defects and an acute decrease in global and regional pulmonary microvascular perfusion. This pilot work will provide the experience and data to support subsequent funding applications powered to definitively establish the acute toxicities of e-cigarette vapor of various compositions (e.g., with and without nicotine, with and without flavoring) in persons with and without chronic lung diseases (e.g., asthma) on pulmonary ventilation and microvascular perfusion. Furthermore, confirmation of our hypotheses in this modest sample would provide important preliminary evidence of e-cigarette pulmonary toxicities to inform interim regulatory decisions, as well as potentially generating vivi images of e-cigarette harms that may be meaningful to the general public and therefore suitable for use in public education campaigns.

 描述（由申请人提供）：确定电子烟对年轻人的急性肺部毒性具有重大公共卫生意义。电子烟蒸气含有已知的有毒物质，预计会对呼吸道和肺微血管造成急性损害。磁共振成像（MRI）和血管造影（MRA）措施是检测和表征预期急性肺部毒性的有前途的方法。超极化氦 (3He) 增强 MRI 可能比肺活量测定更敏感，3He 增强 MRI 已用于证明正常健康人的通气缺陷程度。肺活量测定；测量支气管扩张剂和醋甲胆碱刺激前和哮喘患者的通气变化；同时预测慢性阻塞性肺病患者的肺部住院情况。最近，我们的团队开发了一种基于钆 (Gd) 增强 MRA 的肺微血管血流量的创新测量方法，我们发现这种方法在早期慢性阻塞性肺疾病 (COPD) 和慢性阻塞性肺疾病 (COPD) 中明显异常。然而，这些敏感的、非侵入性的、可重复的和可重复的测量方法均未用于治疗肺气肿。因此，我们建议开展一项试点研究，使用金标准随机交叉设计来测试标准化电子烟暴露对 3He 增强 MRI 和 Gd 增强 MRA 对 10 名健康年轻成人的急性影响。我们认为，电子烟蒸气吸入将导致全球和区域通气缺陷急剧增加，以及全球和区域肺微血管灌注急剧减少。这项试点工作将为支持后续的资助申请提供经验和数据。最终确定各种成分的电子烟蒸气的急性毒性（例如，有或没有 此外，在这个适度样本中证实我们的假设将为电子烟肺部毒性提供重要的初步证据，以供参考。临时监管决定，以及可能生成电子烟危害的生动图像，这些图像可能对公众有意义，因此适合在公共教育活动中使用。