Using PET to Measure Pulmonary Oxidative Stress in E-cigarette Users

使用 PET 测量电子烟使用者的肺氧化应激

• 批准号: 10219697
• 负责人: Reagan R Wetherill
• 金额: $ 15.79万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219697
• 关键词: Adult Respiratory Distress Syndrome; Aerosols; Amines; Animal Model; Asthma; Awareness; Biochemical; Biological Markers; Blood; Blood specimen; Chest; Chronic; Chronic Obstructive Airway Disease; Cigarette; Cigarette Smoker; Development; Disease; Disease Progression; Electronic Nicotine Delivery Systems; Electronic cigarette; Emission-Computed Tomography; Enzymes; Epithelial; Epithelium; Exhalation; Exhibits; Forced expiratory volume function; Goals; Health; Heart Transplantation; Hour; Human; IL8 gene; Image; Inflammation; Inflammatory; Inhalation; Interleukin-1 beta; Letters; Lipopolysaccharides; Lung; Lung Inflammation; Lung diseases; Malignant Neoplasms; Marketing; Measurement; Measures; NOS2A gene; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthetase Inhibitor; Oxidative Stress; Pathogenesis; Pathway interactions; Patient Self-Report; Poison; Positron-Emission Tomography; Pre-Clinical Model; Protein Isoforms; Public Health; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; Pulmonary function tests; Radiolabeled; Research; Research Design; Respiratory physiology; Risk; Scanning; Severity of illness; Smoking; Smoking Status; Spirometry; Structure of parenchyma of lung; TNF gene; Time; Tobacco smoking behavior; Toxic effect; United States; Visualization; Vital capacity; X-Ray Computed Tomography; Youth; airway inflammation; cigarette smoke; cigarette smoking; cytokine; electronic cigarette user; electronic liquid; experience; exposure to cigarette smoke; human data; in vivo; inflammatory lung disease; innovation; lung imaging; lung injury; lung volume; non-smoker; non-smoking; novel; novel imaging technique; radiotracer; respiratory health; response; smoking-related lung disease; specific biomarkers; vape pens; young adult

Worldwide, more than 3.5 million people die annually from smoking-related lung diseases. Although public awareness regarding smoking-related risks has increased and tobacco smoking has declined in the United States, the use of Electronic Nicotine Delivery Systems, or ENDS (e.g., e-cigarettes, vape pens), has dramatically increased, particularly among youth and young adults. The increased popularity of ENDS is due in part to targeted marketing efforts asserting that these products represent a “safer alternative” to traditional cigarettes. To date, however, there is a paucity of human data on the potential toxicity of ENDS use, particularly relative to that of cigarette smoke. Inducible nitric oxide synthase (iNOS) is an enzyme that is constitutively expressed in lung epithelium and is specific for inflammation, a common pathway for many types of lung disease. We propose to measure lung inflammation using Positron Emission Tomography (PET) imaging with [18F]-6- (1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine ([18F]NOS), an exciting new PET radiotracer that targets the inducible isoform of nitric oxide synthase. The goal of the proposed study is to leverage our experience with this novel imaging technique to compare, for the first time, lung inflammation in ENDS users with cigarette smokers and nonsmokers. Specifically, we will quantify, localize, and compare, for the first time, lung inflammation in ENDS users with cigarette smokers and nonsmokers using PET lung imaging with [18F]NOS (Aim 1) and examine and compare biomarkers of airway (fractional exhaled nitric oxide (FeNO)) and lung inflammation (i.e., pro- inflammatory cytokines (TNF-α, IL-1β, IL-8)) and lung function (as measured by forced expiratory volume (FEV) and forced vital capacity (FVC) using spirometry) (Aim 2). To accomplish these goals, 60 subjects [3 groups of 20: ENDS users, traditional cigarette smokers, and nonsmoking controls] will be carefully screened and smoking status will be biochemically verified. Subjects will complete self-report measures, undergo a one-hour [18F]NOS PET/CT (computed tomography) scan of the chest, provide a breath and blood sample for measurement of biomarkers of airway and lung inflammation, and complete lung function tests using spirometry. The proposed study would be the first use of [18F]NOS PET lung imaging to localize and quantify the extent of lung inflammation, examine biomarkers of airway and lung inflammation, and lung function due to ENDS use and cigarette smoking. By measuring specific inflammatory effects of ENDS use on lung tissue, our proposal directly supports the FDA's goal of developing ENDS product standards to protect public health.

全球每年有超过 350 万人死于与吸烟相关的肺部疾病。虽然公开 在美国，人们对吸烟相关风险的认识有所提高，吸烟率有所下降 各州使用电子尼古丁输送系统（ENDS）（例如电子烟、电子烟笔）已 急剧增加，特别是在青年和年轻人中。 ENDS 的日益普及是由于 有针对性的营销努力的一部分，声称这些产品代表了传统产品的“更安全的替代品” 香烟。然而，迄今为止，关于电子尼古丁传送系统使用潜在毒性的人类数据还很缺乏，特别是 相对于香烟烟雾而言。诱导型一氧化氮合酶 (iNOS) 是一种组成型酶 在肺上皮中表达，对炎症具有特异性，炎症是许多类型肺部疾病的常见途径。 我们建议使用[18F]-6-正电子发射断层扫描（PET）成像来测量肺部炎症 (1/2)(2-氟-丙基)-4-甲基吡啶-2-胺 ([18F]NOS)，一种令人兴奋的新型 PET 放射性示踪剂，针对 一氧化氮合酶的诱导亚型。拟议研究的目标是利用我们在这方面的经验 新颖的成像技术首次将 ENDS 使用者与吸烟者的肺部炎症进行比较 和不吸烟者。具体来说，我们将首次量化、定位和比较肺部炎症 使用 [18F]NOS 进行 PET 肺部成像（目标 1）对吸烟者和不吸烟者进行 ENDS 用户检查 并比较气道的生物标志物（呼出一氧化氮分数（FeNO））和肺部炎症（即促 炎症细胞因子（TNF-α、IL-1β、IL-8））和肺功能（通过用力呼气量 (FEV) 测量） 和使用肺活量测定法测定用力肺活量 (FVC)）（目标 2）。为了实现这些目标，60 名受试者 [3 组 20：ENDS使用者、传统吸烟者和非吸烟控制者]将被仔细筛查并吸烟 状态将得到生化验证。受试者将完成自我报告措施，接受一小时的 [18F]NOS 胸部 PET/CT（计算机断层扫描）扫描，提供呼吸样本和血液样本以测量 气道和肺部炎症的生物标志物，以及使用肺活量测定法进行的完整肺功能测试。拟议的 该研究将首次使用 [18F]NOS PET 肺部成像来定位和量化肺部炎症的程度， 检查气道和肺部炎症的生物标志物，以及由于电子尼古丁传送系统的使用和吸烟而导致的肺功能。 通过测量 ENDS 使用对肺组织的特定炎症影响，我们的提案直接支持 FDA 的建议 制定 ENDS 产品标准以保护公众健康的目标。