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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

基本信息

批准号：
10018085
负责人：
Reagan R Wetherill
金额：
$ 20.31万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018085
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

项目摘要

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.

全世界每年有350多万人死于与吸烟有关的肺部疾病。虽然公共