Cardiopulmonary effects induced by electronic-cigarette and JUUL aerosols in both in vivo and in vitro models.

电子烟和 JUUL 气雾剂在体内和体外模型中诱导的心肺效应。

• 批准号: 10563196
• 负责人: Alexandra Noel
• 金额: $ 16.99万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10563196
• 关键词: Acute-Phase Proteins; Address; Adult; Aerosols; Age; Air; Aldehydes; American; Award; Bioinformatics; Biological Assay; Biological Markers; Biology; Blood Vessels; Canada; Candy; Cardiopulmonary; Cardiovascular system; Categories; Cell Survival; Cells; Characteristics; Chemicals; Chronic; Cigarette; Clinical; Complement; Development; Devices; Doctor of Philosophy; Electronic Nicotine Delivery Systems; Electronic cigarette; Endothelial Cells; Endothelium; Epithelial Cells; Evaluation; Exposure to; Female; Fibrinogen; Flavoring; Flow Cytometry; Fruit; Funding; Future; Gene Expression; Generations; Genes; Goals; Health; Health Policy; Heart; High Pressure Liquid Chromatography; High School Student; Human; Immune; Immunity; Immunology; Immunosuppression; In Vitro; Individual; Inflammation; Inhalation; Inhalation Exposure; Inhalation Toxicology; Institution; JUUL; JUUL vapor; Knowledge; Learning; Liquid substance; Louisiana; Lung; Mainstreaming; Measures; Mentors; Middle School Student; Mus; Myocardial Infarction; Nicotine; Oxidative Stress; P-Selectin; Peptidyl-Dipeptidase A; Phenotype; Physiological; Plasma; Play; Population; Predictive Value; Prevalence; Propylene Glycols; Public Health; Publishing; Pulmonary Heart Disease; Recovery; Regulation; Renin; Renin-Angiotensin System; Reporting; Research; Risk; Role; Science; Scientist; Smoking; Sodium Chloride; Solid; Stephania; Structure; Supervision; System; Techniques; Teenagers; Testing; Time; Tobacco; Toxic effect; Training; Training Activity; Universities; Vulnerable Populations; Western Blotting; asthmatic; base; biomarker identification; biomarker panel; cardiovascular effects; career; career development; cigarette smoke; cigarette smoking; cigarette user; cytotoxicity; design; e-cigarette aerosols; early detection biomarkers; electronic liquid; environmental tobacco smoke; genotoxicity; in vitro Model; in vivo; in vivo Model; inflammatory marker; innovation; lung development; lung health; male; mouse model; nano-string; nanoparticle; non-cigarette tobacco product; non-smoking; preadolescence; predictive marker; professor; programs; protein expression; pulmonary function; response; symposium; systemic inflammatory response; titanium dioxide; tobacco exposure; tobacco products; tobacco regulatory science; vegetable glycerin; von Willebrand Factor

PROJECT SUMMARY/ABSTRACT Candidate background: I received my PhD from the University of Montreal (Canada) with a dissertation on pulmonary responses induced by inhaled TiO2 nanoparticles. This research provided me with a solid expertise in lung biology and inhalation toxicology. During my post-doctorate at Louisiana State University (LSU) under the supervision of Dr. Arthur Penn, I received high quality training in tobacco science, including on second-hand smoke and electronic-cigarettes (e-cigs). I am currently an Assistant Professor at LSU, with a research program that focuses on electronic nicotine delivery systems (ENDS) and their pulmonary health effects. Career goals and objectives: My long-term career goals are to become a well-funded independent scientist in the fields of tobacco regulatory science, as well as to attain a tenured Professorship in a research-intensive academic institution. My research goals are to enhance our understanding of the impact of e-cig and JUUL aerosol exposures on lung development and on cardiopulmonary responses. This mentored award will support my career goals by providing protected time to learn new techniques and expertise from my mentoring team. Career development and training activities: I plan to use this mentored award to gain expertise in lung immunology and cardiovascular effects caused by exposures to tobacco-related products to complement my expertise in tobacco-related pulmonary effects. This will be supported by my mentoring team. Dr. Stephania Cormier will be my primary mentor in flow cytometry and lung immunity. Dr. Kent Pinkerton’s mentoring will allow me to expand from solely pulmonary assessment to cardiovascular evaluations of effects induced by ENDS. Dr. Tammy Dugas will be my primary mentor in assessing vascular function in mouse models following exposures to ENDS aerosols. I will also complete a bioinformatics course, attend seminars and present at conferences. Research strategy – Summary: The prevalence of ENDS use in the US is 8 million adults, of whom 70% are dual-users of classic cigarettes and e-cigs. Little is known regarding the cardiopulmonary effects due to chronic inhalation of ENDS aerosols. Clinical evidence demonstrates declines in lung function and increases in risks of myocardial infarction in healthy dual-users. Since biomarkers of harm with predictive value for cardiopulmonary diseases in dual-users exist, we hypothesize that these biomarkers can serve as a basis for the evaluation of cardiopulmonary toxicity related to long-term inhalation exposures to e-cig or JUUL in single-users. We will study how two ENDS products of different design -- 1) open system e-cig devices, and 2) closed system JUUL devices -- impact individual or combinations of the constituents found in these aerosols, and their toxicity. Our goals are A) to examine the roles that e-liquid constituents play in the chemical profile and in vitro toxicity of ENDS aerosols; and B) to define a panel of biomarkers for cardiopulmonary effects following exposures to either dual- use of cigarettes and e-cigs, or sole exposures to e-cig or JUUL aerosols using in vivo models. Thus, this study has a high societal impact since it will help inform the regulatory agencies and the 8 million adults ENDS users.

项目总结/摘要 候选人背景：我在蒙特利尔大学（加拿大）获得博士学位，论文是关于 吸入TiO 2纳米颗粒诱导的肺反应。这项研究为我提供了坚实的专业知识 肺生物学和吸入毒理学。在路易斯安那州立大学（LSU）攻读博士后期间， 在亚瑟·佩恩博士的指导下，我接受了烟草科学方面的高质量培训，包括二手烟草培训 电子烟（Electronic Cigs）我目前是路易斯安那州立大学的助理教授， 电子尼古丁输送系统（ENDS）及其对肺部健康的影响。 职业目标：我的长期职业目标是成为一名资金充足的独立科学家， 烟草监管科学领域，以及获得终身教授在研究密集型 学术机构。我的研究目标是提高我们对电子烟和JUUL的影响的理解 气溶胶暴露对肺发育和心肺反应的影响。这个指导奖将支持 我的职业目标，提供保护的时间来学习新的技术和专业知识，从我的指导团队。 职业发展和培训活动：我计划利用这一指导奖获得肺专业知识 烟草相关产品对免疫和心血管的影响， 专门研究烟草对肺部的影响这将得到我的指导团队的支持。Stephania博士 Corpus将是我在流式细胞术和肺免疫方面的主要导师。肯特·平克顿博士的指导 我希望从单纯的肺部评估扩展到对ENDS引起的心血管影响的评估。博士 Tammy Dugas将是我在评估暴露后小鼠模型血管功能方面的主要导师 结束气溶胶。我还将完成生物信息学课程，参加研讨会并出席会议。 研究策略-总结：在美国，ENDS使用的流行率为800万成年人，其中70%是 经典香烟和电子烟的双重使用者。关于慢性呼吸道感染对心肺功能的影响知之甚少。 吸入ENDS气溶胶。临床证据表明，肺功能下降， 健康的双重使用者的心肌梗死。由于具有心肺功能预测价值的伤害生物标志物 存在双重使用者的疾病，我们假设这些生物标志物可以作为评估 与单用户长期吸入暴露于电子烟或JUUL相关的心肺毒性。我们将研究 两种不同设计的ENDS产品-- 1）开放系统电子烟装置和2）封闭系统JUUL装置 - 影响这些气溶胶中发现的成分的单个或组合及其毒性。我们的目标是 A）检查电子液体成分在ENDS的化学特征和体外毒性中发挥的作用 气溶胶;和B）定义暴露于双重- 使用香烟和电子烟，或使用体内模型单独暴露于电子烟或JUUL气雾剂。因此，本研究 具有很高的社会影响力，因为它将有助于向监管机构和800万成年ENDS用户提供信息。