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

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.