Metal Exposure and Subclinical Lung Disease in Adult E-cigarette Users

电子烟（e-cig）的使用很普遍，特别是在青少年和年轻人中， 与电子烟和Vaping相关的肺损伤（EVALI）。填补在以下方面的知识空白： 电子烟使用的呼吸健康风险，我们提出了一项辅助研究R01ES029967（第6百分位数，下降） 2019年），以评估电子烟使用与亚临床肺损伤之间的关联，以及潜在的 电子烟气溶胶中所含金属的贡献。人们对通过电子烟吸入金属的风险知之甚少， 尽管至少有一例EVALI病例与电子烟笔中的钴有关。我们的团队已经证明电子烟的气溶胶 通常含有潜在的有毒金属水平，与肺部疾病有联系。因此，我们建议 研究电子烟使用者的亚临床肺部疾病的证据， 金属测量亚临床肺部疾病可以使用定量成像检测和表征 肺结构和功能的测量方法，这是由我们的研究小组开创的。我们已经表明 计算机断层扫描（CT）和磁共振成像（MRI）上的肺部特征预测 临床肺病我们还发现，这些成像措施可以检测电子烟和金属相关的 亚临床肺损伤这项研究将使用亚临床肺病的影像学指标来支持 关于使用电子烟和电子烟相关金属的长期临床呼吸风险的推断 exposure.母研究R01ES029967将研究电子烟使用、金属和 通过在纽约市招募520名参与者，年龄18 - 50岁， 包括130名从未吸烟的电子烟使用者，130名目前的电子烟使用者/前吸烟者， 130名双重当前vapers/当前吸烟者和130名从不vapers/从不吸烟者。测量将包括 电子烟气溶胶以及血液或尿液中金属的黄金标准量化，除了详细的 评估内皮健康和临床前心血管疾病。通过这项辅助研究，我们 建议增加创新的超低剂量CT（N = 400名参与者）和心肺MRI（N = 200名参与者 参与者）-加上肺功能测定、DLCO和相关混杂因素-以检验以下目的： 目的1：确定电子烟使用与亚临床肺部疾病的影像学指标之间的关系。 目的2：确定金属暴露与亚临床肺部疾病的影像学指标之间的关系。 探索性目标3：探索金属暴露对目标1关联的影响和调节。 这项研究将解决有关使用电子烟的呼吸系统健康风险的主要知识缺口， 在年轻人中越来越常见。它将测试关于电子烟和亚临床的强大生物学假设 使用调查小组开发和应用的创新成像措施来治疗肺部疾病;此外， 将研究金属暴露的作用，一个既定的肺毒素，在电子烟相关的肺损伤。的 研究结果将有助于为公共卫生运动和有关电子烟的法规提供信息。

E-cigarette (e-cig) use is common, particularly among adolescents and young adults, and has been associated with E-cigarette and Vaping Associated Lung Injury (EVALI). To address major gaps in knowledge regarding the respiratory health risks of e-cig use, we propose an ancillary study to R01ES029967 (6th percentile, Fall 2019) to evaluate associations between e-cig use and subclinical lung injury, as well as the potential contribution of metals contained in e-cig aerosols. Risk of inhaling metals via e-cigs is poorly understood, although at least one EVALI case was linked to cobalt in a vape pen. Our team has shown that e-cig aerosols frequently contain potentially toxic levels of metals with established links to lung disease. Hence, we propose to study e-cig users for evidence of subclinical lung disease in the context of state-of-the-science metal measurements. Subclinical lung disease can be detected and characterized using quantitative imaging measures of lung structure and function that have been pioneered by our investigative group. We have shown that lung features on computed tomography (CT) and magnetic resonance imaging (MRI) predict incident clinical lung disease. We have also found that these imaging measures may detect e-cig and metal-related subclinical lung injury. This study will use imaging measures of subclinical lung disease to support inferences regarding the long-term clinical respiratory risks of e-cig use and e-cig-related metal exposure. Parent study R01ES029967 will examine the relationships between e-cig use, metals, and subclinical cardiovascular disease by recruiting 520 participants in New York City, ages 18-50 years old, including 130 current e-cig users (vapers) who never smoked tobacco, 130 current vapers/former smokers, 130 dual current vapers/current smokers, and 130 never vapers/never smokers. Measurements will include gold-standard quantification of metals in e-cig aerosols as well as in blood or urine, in addition to detailed assessments of endothelial health and preclinical cardiovascular disease. With this ancillary study, we propose to add innovative ultra-low dose CT (N=400 participants) and cardiopulmonary MRI (N=200 participants) – plus spirometry, DLCO, and relevant confounders – to test the following Aims: Aim 1: Determine the associations of e-cig use with imaging measures of subclinical lung disease. Aim 2: Determine the associations of metal exposures with imaging measures of subclinical lung disease. Exploratory Aim 3: Explore effect modification and mediation of Aim 1 associations by metal exposures. This study will address major gaps in knowledge regarding the respiratory health risks of e-cig use, which is increasingly common in young adults. It will test robust biological hypotheses regarding e-cigs and subclinical lung disease using innovative imaging measures developed and applied by the investigative team; moreover, it will examine the role of metal exposure, an established pulmonary toxin, in e-cig-related lung injury. The results will be suitable to help inform public health campaigns and regulation regarding e-cigarettes.