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: 10371746
• 负责人: Laura Elise Crotty Alexander
• 金额: $ 12.17万
• 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/10371746
• 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; Country; Data; Development; Devices; Disease; Drug Delivery Systems; Drug usage; Electronic cigarette; Ensure; Eosinophilia; Eotaxin; Epidemic; Evolution; Extrinsic asthma; Faculty; Feeling; Fibrosis; Financial compensation; Generations; Glycerol; Grant; Health; Heart; Host Defense; Human; IL8 gene; Immune; Immunologics; Inflammatory; Inhalant dose form; Inhalation; Institutes; Institutional Review Boards; Interleukin-4; Interleukin-5; Interleukin-6; Kidney; Lead; 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; Propylene Glycols; Protocols documentation; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; RANTES; 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; base; 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; high risk population; high school; human subject; immunoregulation; improved; junior high school; 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.

项目摘要/摘要 自从两年半前成为一名副教授以来，我想起了我当助理的那些年 教授并意识到，我对喜悦最伟大的时刻来自于我的学员的成功。他们所处的时刻 获得了他们的第一个奖学金，获得了他们的第一个教员职位，第一篇有影响力的论文是 接受的一切在我的记忆中闪耀着光芒。同样重要的是学员前来观看的时刻 因为他们感觉不成功或没有动力，他们觉得他们不会在 学者们，通过我们的交谈，他们站了起来，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，我担心投入到 管理和临床工作，并相信通过此K24获得保护时间将直接导致 在三个方面的发展和丰富：1.指导，2.进行前沿小说研究，3. 学习新的以病人为中心的研究技能。我真的相信，把更多的时间花在指导上将会 在三者中影响最大，因为加强和支持热情、聪明、 与我的研究相比，敬业的受训者将在医学界和学术界产生更广泛的影响。在……里面 根据研究，电子烟是2007年进入美国的药物输送(蒸发)设备，已经 在使用方面呈爆炸式增长，特别是在从不吸烟的青少年和年轻人中。我们没有 关于蒸发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 我们在加州大学圣迭戈分校现有的年轻电子烟尿布队列，这里提出的研究可以获得纵向 通过让这些受试者在1年和2年后返回，从而给出3个时间点，在这3个时间点上呼吸道发生变化 炎症，微生物组和反应性，以及全身炎症可以被定义。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宣传活动， 使许多人相信这些设备没有不良影响。但哮喘患者有呼吸道和 全身性炎症，因此他们可能更容易受到促炎和 汽化的免疫调节作用。通过再次利用正在进行的以患者为中心的研究 我们的团队，我建议在这里招募TH2高过敏性哮喘的蒸发和非蒸发受试者来评估 吸入电子烟对他们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以患者为中心的研究和分析的能力 从而产生尽可能高质量的相关数据。在我自己导师的支持下(阿图尔·马尔霍特拉博士 和Victor Nizet)，我相信，UCSD的支持，我现有的出色的研究团队和即将到来的学员 这位K24的支持将使其成为一名导师、研究员和终身学习者成为可能。