The adverse chronic effects of e-cigarettes: puff profiles, sex, genetics, and flavorings as modifying factors

电子烟的慢性不良影响：吸食特征、性别、遗传和调味剂作为改变因素

基本信息

批准号：
9994260
负责人：
Terry Gordon
金额：
$ 37.71万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9994260
关键词：
3-nitrotyrosine Acetaldehyde Acetylcysteine Acrolein Acute Adverse effects Aerosols Animal Model Animal Testing Applications Grants Biological Markers Blood Bronchoalveolar Lavage Cardiac Cardiopulmonary Cardiovascular Physiology Chronic Cigarette DNA Adducts Dangerousness Deoxyguanosine Development Devices Diacetyl Electronic cigarette Exogenous Factors Exposure to Female Flavoring Formaldehyde Foundations Gender Generations Genetic Genetic Heterogeneity Glutathione Glycerol Health Health Policy Heart Heart Rate Heating Heterogeneity Human Inbred Strain Inflammatory Inhalation Exposure Injury Leukocytes Lipid Peroxides Long-Term Effects Lung Lung Inflammation Measures Mouse Strains Mus Nicotine Organ Oxidative Stress Pathway interactions Phenotype Poison Population Propylene Glycols Proteins Public Health Research Sex Factors Smoker Smoking Structure of parenchyma of lung Subgroup Temperature Testing Tobacco Toxic effect Toxicology adduct base biomarker performance carbonyl compound cardiovascular effects cigarette smoke cigarette smoking cinnamic aldehyde combustible cigarette design e-cigarette aerosols electronic cigarette use electronic liquid epidemiology study experimental study follow-up genotypic sex hazard heart rate variability human subject male non-smoker phenotypic biomarker pulmonary function response sex urinary vaping voltage

项目摘要

Abstract Electronic cigarettes (e-cigs), were introduced to the U.S. market only 10 years ago and are markedly different from traditional tobacco-based cigarettes. Whereas traditional cigarettes are smoked through combustion, e-cigarettes are “vaped” (i.e., heated), and the resultant aerosols contain a far smaller number of potentially toxic chemicals, such as nicotine and flavorings (e.g., cinnamaldehyde and diacetyl), as well as byproducts (e.g., acrolein and formaldehyde) caused by the potential overheating of these agents, propylene glycol, and glycerin. Thus, although e-cigarettes are widely believed and marketed as a safer alternative to cigarette smoking, the actual danger posed by its use remains largely unexplored. As the use of e-cigs steadily rises, the number of health effects studies is still relatively small and have focused on short term effects. These studies, however, have demonstrated adverse pulmonary and cardiovascular effects in human subjects and test animals. To date, some long term human health effects studies have investigated e- cigarettes as cessation devices, but such epidemiology studies are confounded by the `poly-use' of e- cigarettes and previous (and possibly concurrent) traditional tobacco cigarettes. Therefore, the studies proposed in this grant application will avoid this confounding and utilize established animal models, previously used in long-term tobacco studies, to investigate the adverse cardiopulmonary effects of e-cigarettes after chronic inhalation exposures. In particular, the proposed experiments are designed to discern: 1) the toxicity of the e-liquid aerosols themselves, with and without added flavorings, generated at different voltages (i.e. heating coil temperatures); and 2) the contribution of innate modifying factors, such as sex, glutathione biomarkers and pathways, and genetics, to e-cigarette toxicity. We will test the overall hypothesis that chronic exposure to e-cigarette aerosols produces adverse cardiopulmonary effects and that these effects are modified by innate factors, such as genetic heterogeneity and sex (i.e., gender), and exogenous factors, such as flavorings and e-cigarette coil temperature.

抽象的电子烟（电子烟）仅在10年前才引入美国市场不同于传统的烟草香烟。而传统香烟则通过燃烧，电子烟是“蒸发的”（即加热），并且所得的气溶胶包含少量数量潜在的有毒化学物质，例如尼古丁和调味剂（例如，肉桂醛和二乙酰基），以及副产物（例如丙烯醛和甲醛）由这些试剂，丙烯的潜在过热引起甘油和甘油。因此，尽管电子烟被广泛认为和销售是更安全的替代品吸烟，其使用所带来的实际危险仍然很出乎意料。作为电子烟的使用稳步上升，健康效应研究的数量仍然相对较少，并且专注于短期效果。然而，这些研究表明人类的肺部和心血管影响不良受试者和测试动物。迄今为止，一些长期的人类健康效应研究已经调查了E- 香烟作为戒烟装置，但是这种流行病学研究被电子的“多用途”混淆了文明和以前的（可能并发）传统烟烟。因此，研究在本赠款申请中提出的建议将避免这种混杂并利用已建立的动物模型，以前用于长期烟草研究，以研究电子烟的不良心肺作用慢性吸入暴露。特别是，提出的实验旨在辨别：1）电子液体气溶胶本身，有和没有添加的口味，以不同的电压产生（即加热线圈温度）； 2）先天修改因素（例如性，谷胱甘肽）的贡献生物标志物，途径以及遗传学，引起电子烟的毒性。我们将测试慢性的总体假设暴露于电子烟气溶胶会产生不良心肺影响，并将这些作用改变由先天因素，例如遗传异质性和性别（即性别）和外源性因素，例如调味剂和电子烟线圈温度。