Respiratory Effects, Metal and Aldehyde exposure from e-cigarette use in young adults (REMA)

项目摘要 我的长期目标是成为一名独立的调查员，专注于污染物暴露如何对人类健康产生不利影响。 影响呼吸系统健康，并确定有效减少此类接触的措施。我的主要项目 目的是调查关注的化学成分（CCOC）的暴露和毒性，即金属 和醛，以及肺部健康的影响，包括炎症，使用新的和新兴的 电子烟（e-cig）在年轻人中的应用电子烟装置的工作原理是加热一种化学混合物 以产生被使用者吸入的气溶胶。电子烟的使用有所增加，在成年人中， 年龄在18至24岁之间的人最多。最近的电子烟设备，如一次性POD， 受欢迎程度，但目前尚不清楚这些新设备的设计特点是否与用户 vaping方案影响CCOC暴露并影响呼吸健康。因此，我的具体目标是：1） 评估电子烟使用与CCOC暴露和效果之间的关系，2）评估电子烟的关联 与呼吸结果和炎症标志物一起使用，以及3）评估CCOC暴露作为混合物， 电子烟相关呼吸健康结果的潜在介导者。在这项横断面研究中，为了实现目标1， (K99阶段），将招募150名参与者（75名电子烟使用者，75名非使用者）来评估暴露的生物标志物 （醛、金属）和影响（金属硫蛋白）。这将利用正在进行的EMIT研究， 通过问卷调查、气溶胶样本、生物样本，查看金属接触情况，并收集电子烟使用者的用药方案 （血液、尿液）和肺活量测定。在接受化学分析培训后， 结果和炎症标志物，包括基因表达的变化，一个新的队列的150名参与者（75 电子烟使用者，75名非使用者）将被招募参加目标2（R 00阶段）。这一阶段不仅会收集相同的数据 如目标1中所述，还包括效应和炎症的生物标志物（血液、尿液、FeNO）和基因表达谱（在 鼻上皮细胞）。电子烟使用者是否有呼吸道症状、炎症和基因改变 将评估与非使用者相比的表达谱。合并目标1和2队列（n= 300），目标3 将采用贝叶斯和因果中介方法来评估CCOC暴露是否是积极的， 至少部分解释了电子烟使用对呼吸的影响。的扩散 新的电子烟设备，迫切需要表征暴露和呼吸健康影响， 从他们的使用。本研究有可能生成关键数据，以告知FDA法规， 这将有助于减少接触和健康结果，并遏制年轻人中日益普遍的吸毒现象。通过这个 研究，我的教学课程，以及我的指导团队的指导，包括一位肺病学家， 接触科学家，免疫学家，分析化学家和环境流行病学家，我将获得关键的 成为一名成功的环境健康和烟草控制独立研究人员所需的技能。

PROJECT SUMMARY My long-term goal is to become an independent investigator focusing on how pollutant exposures may adversely affect respiratory health and identify measures to effectively mitigate such exposures. My primary project objective is to investigate the exposure and toxicity of chemical constituents of concern (CCOC), namely metal and aldehydes, as well as the pulmonary health effects, including inflammation, of using new and emerging electronic cigarette (e-cig) devices among young adults. E-cig devices work by heating a mixture of chemicals to generate an aerosol that is inhaled by the user. Use of e-cigs has increased and, among adults, remains the highest among those aged 18 to 24 years. More recent e-cig devices such as disposable PODs have grown in popularity, yet it is currently unknown whether these new devices’ design characteristics in conjunction with user vaping regimen impact CCOC exposure and influence respiratory health. Thus, my specific aims are to 1) evaluate the relationship between e-cig use and CCOC exposure and effect, 2) assess the association of e-cig use with respiratory outcomes and inflammatory markers, and 3) assess CCOC exposure as a mixture and potential mediator in e-cig related respiratory health outcomes. In this cross-sectional study, to achieve Aim 1 (K99 phase), 150 participants (75 e-cig users, 75 non-users) will be recruited to assess biomarkers of exposure (aldehydes, metals) and effect (metallothionein) from e-cig use. This will leverage the ongoing EMIT study which looks at metal exposure and collects e-cig user regimen via questionnaire, aerosol samples, biospecimens (blood, urine), and spirometry measures. After receiving training in chemical analysis, respiratory clinical outcomes, and inflammatory markers, including gene expression changes, a new cohort of 150 participants (75 e-cig users, 75 non-users) will be recruited for Aim 2 (R00 phase). This phase will not only collect the same data as in Aim 1 but also biomarkers of effect and inflammation (blood, urine, FeNO) and gene expression profiles (in nasal epithelial cells). Whether e-cig users have increased respiratory symptoms, inflammation and altered gene expression profiles compared to non-users will be evaluated. Combining Aims 1 and 2 cohorts (n= 300), Aim 3 will employ the use of Bayesian and causal mediation methods to assess if CCOC exposure is positively associated with and explains, at least in part, the respiratory effects from e-cig use. With the proliferation of newer e-cig devices, there is an urgent need to characterize exposure and respiratory health effects resulting from their use. This study has the potential to generate critical data to inform FDA regulation to limit adverse exposures and health outcomes and curb the increasing prevalence of use among young adults. Through this research, my didactic coursework, and the guidance of my mentoring team consisting of a pulmonologist, exposure scientist, immunologist, analytical chemist, and environmental epidemiologist, I will acquire critical skills needed to be a successful independent researcher in environmental health and tobacco control.