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

项目总结 我的长期目标是成为一名独立的调查员，专注于污染物暴露可能带来的不利影响 影响呼吸健康，并确定有效减少这种接触的措施。我的主要项目 目的是调查关注的化学成分(CCOC)，即金属的暴露和毒性 和醛，以及对肺部健康的影响，包括炎症，使用新的和新兴的 在年轻人中使用电子烟(e-cig)设备。电子烟设备通过加热混合的化学物质来工作 以产生使用者吸入的气雾剂。电子烟的使用有所增加，在成年人中，电子烟的使用仍然是 在18至24岁的人群中最高。更新的电子烟设备，如一次性吊舱，在 受欢迎，但目前尚不清楚这些新设备的设计特点是否与用户 汽化疗法会影响CCOC暴露并影响呼吸健康。因此，我的具体目标是1) 评估e-cig使用与CCOC暴露和影响的关系；2)评估e-cig的关联性 与呼吸结果和炎症标志物一起使用，以及3)作为混合物评估CCOC暴露和 电子烟相关呼吸健康结果的潜在介体。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CIG使用者和75名非使用者)以评估暴露的生物标志物 (醛、金属)和电子烟使用的影响(金属硫蛋白)。这将利用正在进行的排放研究，该研究 观察金属暴露情况，并通过问卷、气溶胶样本、生物样本收集电子烟使用方案 (血液、尿液)和肺活量测定。在接受化学分析培训后，呼吸系统临床 结果和炎症标记物，包括基因表达变化，150名参与者(75人)的新队列 E-CIG用户，75名非用户)将被招募到AIM 2(R00阶段)。这一阶段不仅会收集相同的数据 与目标1相同，但也包括影响和炎症的生物标记物(血液、尿液、FeNO)和基因表达谱(在 鼻腔上皮细胞)。电子烟使用者的呼吸道症状、炎症和基因改变是否增加？ 将对与非用户进行比较的表达配置文件进行评估。合并目标1和目标2队列(n=300)，目标3 将使用贝叶斯和因果调解方法来评估CCOC暴露是否为积极 与电子烟的使用有关，并至少部分解释了电子烟对呼吸的影响。随着病毒的扩散 较新的电子烟设备，迫切需要确定暴露和由此产生的呼吸健康影响的特征。 从他们的使用中。这项研究有可能产生关键数据，为FDA限制不良反应的法规提供信息 暴露和健康后果，并遏制年轻人中日益普遍的使用情况。通过这件事 研究，我的说教课程，以及我由肺病专家组成的指导团队的指导， 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 具备成为环境健康和烟草控制领域成功的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.