Convergence of Vitamin E, THC, Nicotine, Propylene Glycol and Glycerin Effects on Lung Inflammation When Vaped

维生素 E、THC、尼古丁、丙二醇和甘油的综合作用对电子烟时肺部炎症的影响

• 批准号: 10546469
• 负责人: Laura Elise Crotty Alexander
• 金额: $ 12.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-05 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10546469
• 关键词: Acute; Adolescent and Young Adult; Adverse effects; Advertising; Aerosols; Affect; Age; Age Years; Area; Asthma; Award; Back; Belief; CCL2 gene; Cannabinoids; Cell physiology; Cells; Chemicals; Chronic; Chronic Disease; Clinical; Clinical Research; Compensation; Country; Data; Dedications; Development; Devices; Disease; Drug Delivery Systems; Drug usage; Electronic cigarette; Ensure; Eosinophilia; Eotaxin; Epidemic; Evolution; Explosion; Extrinsic asthma; Faculty; Feeling; Fibrosis; Generations; Glycerol; Grant; Health; Heart; High School Student; Host Defense; Human; IL8 gene; Immune; Immunologics; Inflammatory; Inhalant dose form; Inhalation; Institutional Review Boards; Interleukin-4; Interleukin-5; Interleukin-6; Kidney; Learning; Life; Liver; Longitudinal Studies; Lung; Marijuana Smoking; Medicine; Memory; Mentors; Mentorship; Nasal Epithelium; National Heart, Lung, and Blood Institute; Nicotine; Paper; Patients; Persons; Phenotype; Physiological; Plasma; Population; Positioning Attribute; Predisposition; Productivity; Propylene Glycols; Protocols documentation; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; RANTES; Recontacts; Recruitment Activity; Research; Research Design; Research Personnel; Running; Safety; Saliva; Smoke; Spirometry; Sputum; Techniques; Tetrahydrocannabinol; Time; Tobacco; Tobacco Industry; Training Support; Translational Research; Visit; Vitamin E; Work; age group; airway inflammation; antimicrobial; asthmatic; body system; career; cigarette smoke; cohort; combustible cigarette; coronavirus disease; cytokine; design; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; eosinophil; epidemiologic data; experience; health assessment; high risk population; human subject; immunoregulation; improved; lung injury; marijuana user; methacholine; microbiome; mid-career faculty; monocyte; neutrophil; never smoker; non-smoking; novel; patient oriented; patient oriented research; periostin; professor; recruit; sex; skills; success; systemic inflammatory response; transcriptome sequencing; vaper; vaping; vaping THC; young adult

PROJECT SUMMARY/ABSTRACT Since becoming an Associate Professor two and a half years ago, I think back to my years as an Assistant Professor and realize that my greatest moments of joy came from my mentee’s successes. Moments where they were awarded their first grant, obtained their first faculty position and a high-impact first authored paper was accepted all shine brightly in my memories. Equally important were the moments where a trainee came to see me because they were feeling unsuccessful or unmotivated, and they felt they were not going to succeed in academics, and through our conversation they arose, reassured about their good ideas, skill set and ability to move forward in a positive and productive way. Looking forward, I worry about the amount of time committed to administrative and clinical efforts and believe that obtaining protected time via this K24 will directly lead to development and enrichment in three areas: 1. Mentoring, 2. Conducting cutting-edge novel research, and 3. Learning new patient oriented research skills. I truly believe that expanding my time dedicated to mentorship will have the greatest impact out of the three, because enhancing and supporting the training of passionate, clever, dedicated trainees will lead to broader effects across medicine and academics relative to my research alone. In terms of research, e-cigarettes are drug delivery (vaping) devices that entered the country in 2007 and have exploded in terms of use, especially in adolescents and young adults whom have never smoked. We have no longitudinal data on the health effects of vaping, particularly on lung and systemic inflammation. By leveraging our existing cohort of young e-cigarette vapers at UCSD, the research proposed here can obtain longitudinal data by having these subjects return at 1 and 2 years, thus giving 3 timepoints across which changes in airway inflammation, microbiome and reactivity, and systemic inflammation can be defined. These data will help us understand which chronic diseases will arise from chronic e-cigarette use. Asthmatics are using e-cigarettes at a high rate, most likely because of the successful advertising campaigns tobacco companies have run, convincing many of the lack of adverse effects of these devices. But patients with asthma have airways and systemic inflammation, thus they are likely to be more susceptible to the pro-inflammatory and immunomodulatory effects of vaping. By again leveraging the ongoing patient-oriented research conducted by our team, I propose here to recruit vaping and non-vaping subjects with TH2-high allergic asthma to assess the effects of e-cigarette aerosol inhalation on their underlying disease state. Finally, I propose to dive deeper into clinical research design and analysis, to improve my ability to conduct high level patient oriented research and thus yield the highest quality, relevant data possible. With the support of my own mentors (Drs. Atul Malhotra and Victor Nizet), the support of UCSD, my existing fantastic research team and the mentees to come, I believe the support of this K24 will make it possible to thrive as a mentor, researcher and life-long learner.

项目概要/摘要 成为副教授两年半以来，我回想起自己担任助理的岁月 教授并意识到我最大的快乐时刻来自于我的学员的成功。他们的时刻 获得了他们的第一笔资助，获得了他们的第一个教职职位，并且发表了一篇具有高影响力的第一作者论文 接受我记忆中的一切灿烂光芒。同样重要的是实习生来看的时刻 我因为他们感到不成功或没有动力，他们觉得自己不会成功 学者们，通过我们的谈话，他们对自己的好想法、技能和能力感到放心。 以积极和富有成效的方式前进。展望未来，我担心投入的时间 行政和临床工作，并相信通过 K24 获得保护时间将直接导致 三个领域的发展和丰富：1. 指导，2. 进行前沿小说研究，3. 学习新的以患者为导向的研究技能。我坚信，延长我用于指导的时间将会 在这三者中影响最大，因为加强和支持对充满激情、聪明、 相对于我的研究而言，专注的学员将在医学和学术界产生更广泛的影响。在 从研究角度来看，电子烟是2007年进入国内的药物输送（vaping）设备， 使用量呈爆炸式增长，特别是在从未吸烟的青少年和年轻人中。我们没有 关于电子烟对健康影响的纵向数据，特别是对肺部和全身炎症的影响。通过利用 我们在加州大学圣地亚哥分校现有的年轻电子烟吸烟者队列中，这里提出的研究可以获得纵向研究 通过让这些受试者在 1 年和 2 年返回来获取数据，从而给出气道变化的 3 个时间点 可以定义炎症、微生物组和反应性以及全身炎症。这些数据将帮助我们 了解长期使用电子烟会引发哪些慢性疾病。哮喘患者正在使用电子烟 高比率，很可能是因为烟草公司开展了成功的广告活动， 令人信服的是，这些设备缺乏不利影响。但哮喘患者有呼吸道和 全身炎症，因此他们可能更容易受到促炎和 电子烟的免疫调节作用。通过再次利用正在进行的以患者为导向的研究 我们的团队，我在这里建议招募患有 TH2 高过敏性哮喘的电子烟和非电子烟受试者来评估 电子烟气雾吸入对其潜在疾病状态的影响。最后，我建议更深入地探讨 临床研究设计和分析，以提高我进行高水平的以患者为导向的研究和分析的能力 从而产生尽可能最高质量的相关数据。在我自己的导师（Atul Malhotra 博士）的支持下 和维克多·尼泽），加州大学圣地亚哥分校的支持，我现有的出色的研究团队和即将到来的学员，我相信 K24 的支持将使其成为一名导师、研究员和终身学习者。