Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study

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 DESCRIPTION (provided by applicant): Determination of the acute pulmonary toxicities of e-cigarettes in young adults is of major public health importance. E-cigarette vapor contains established toxicants which may be anticipated to cause acute damage to the airways and the pulmonary microvasculature resulting in the eventual development of chronic lung disease, for which there remain few effective therapies. Magnetic resonance imaging (MRI) and angiography (MRA) measures are promising approaches to detecting and characterizing the anticipated acute pulmonary toxicities of e-cigarettes. Hyperpolarized helium (3He)-enhanced MRI may be more sensitive than spirometry, a global lung function measure, for determination of airway toxicities. 3He-enhanced MRI has been used to demonstrate the extent of ventilation defects in healthy persons with normal spirometry; to measure ventilation changes in asthmatics pre- and post-challenge with bronchodilators and methacholine; and to predict pulmonary hospitalizations in persons with COPD. Meanwhile, until recently, non-invasive measures of pulmonary vascular toxicities were lacking. Our group developed an innovative measure of pulmonary microvascular blood flow on gadolinium (Gd)-enhanced MRA, which we found to be markedly abnormal in early chronic obstructive pulmonary disease (COPD) and emphysema, and to be associated with increased endothelial microparticles, a marker of endothelial dysfunction. Nonetheless, neither of these sensitive, non-invasive, repeatable, and reproducible measures has ever been used to assess e-cigarette toxicities. We therefore propose a pilot study using a gold-standard randomized crossover design to test the acute effects of a standardized e-cigarette exposure on 3He-enhanced MRI and Gd-enhanced MRA in ten healthy, young adult e-cigarette users. We hypothesize that e-cigarette vapor inhalation will result in an acute increase in global and regional ventilation defects and an acute decrease in global and regional pulmonary microvascular perfusion. This pilot work will provide the experience and data to support subsequent funding applications powered to definitively establish the acute toxicities of e-cigarette vapor of various compositions (e.g., with and without nicotine, with and without flavoring) in persons with and without chronic lung diseases (e.g., asthma) on pulmonary ventilation and microvascular perfusion. Furthermore, confirmation of our hypotheses in this modest sample would provide important preliminary evidence of e-cigarette pulmonary toxicities to inform interim regulatory decisions, as well as potentially generating vivi images of e-cigarette harms that may be meaningful to the general public and therefore suitable for use in public education campaigns.