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 (e-cigs) 仅在 10 年前引入美国市场，与传统的烟草香烟不同，传统香烟是通过吸食的。燃烧时，电子烟被“蒸发”（即加热），所产生的气溶胶含有数量少得多的物质。潜在有毒的化学物质，例如尼古丁和调味剂（例如肉桂醛和二乙酰），以及由这些试剂、丙烯的潜在过热引起的副产物（例如丙烯醛和甲醛）因此，尽管电子烟被广泛认为和销售为更安全的替代品。尽管吸烟，但与电子烟的使用一样，其使用所带来的实际危险在很大程度上仍未得到探索。上升，但健康影响研究的数量仍然相对较少，并且一直稳定地关注短期然而，这些研究表明，对人类的肺部和心血管有不良影响。迄今为止，一些长期人类健康影响研究已经调查了电子。香烟作为戒烟工具，但此类流行病学研究因电子烟的“多重使用”而令人困惑。香烟和以前（可能同时存在）的传统烟草香烟。本拨款申请中提出的方法将避免这种混淆并利用先前建立的动物模型用于长期烟草研究，以调查电子烟在吸烟后对心肺的不良影响特别是，所提议的实验旨在辨别：1) 的毒性。电子液体气雾剂本身，无论添加或不添加调味剂，在不同电压下产生（即加热线圈温度）；2）先天改变因素的影响，例如性别、谷胱甘肽我们将检验电子烟毒性的总体假设。接触电子烟气溶胶会对心肺产生不良影响，并且这些影响会被改变由先天因素（例如遗传异质性和性别）和外源因素（例如香料和电子烟线圈温度。