David P. Scieszka, Department of Pharmaceutical Sciences, University of New Mexico School of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Devon Garland, Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, MSC 08 4660, 1 University of New Mexico, Albuquerque, NM, 87131, USA.
Russell Hunter, Department of Pharmaceutical Sciences, University of New Mexico School of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Guy Herbert, Department of Pharmaceutical Sciences, University of New Mexico School of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Selita Lucas, Department of Pharmaceutical Sciences, University of New Mexico School of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Yan Jin, Center for Translational Science, Florida International University, Port St. Lucie, FL, USA.
Haiwei Gu, Center for Translational Science, Florida International University, Port St. Lucie, FL, USA.
Matthew J. Campen, Department of Pharmaceutical Sciences, University of New Mexico School of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Judy L. Cannon, Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, MSC 08 4660, 1 University of New Mexico, Albuquerque, NM, 87131, USA. Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence, University of New Mexico School of Medicine, Albuquerque, NM, USA.Follow

Document Type

Article

Publication Date

5-25-2023

Abstract

Electronic cigarette (Ecig) use has become more common, gaining increasing acceptance as a safer alternative to tobacco smoking. However, the 2019 outbreak of Ecig and Vaping-Associated Lung Injury (EVALI) alerted the community to the potential for incorporation of deleterious ingredients such as vitamin E acetate into products without adequate safety testing. Understanding Ecig induced molecular changes in the lung and systemically can provide a path to safety assessment and protect consumers from unsafe formulations. While vitamin E acetate has been largely removed from commercial and illicit products, many Ecig products contain additives that remain largely uncharacterized. In this study, we determined the lung-specific effects as well as systemic immune effects in response to exposure to a common Ecig base, propylene glycol and vegetable glycerin (PGVG), with and without a 1% addition of phytol, a diterpene alcohol that has been found in commercial products. We exposed animals to PGVG with and without phytol and assessed metabolite, lipid, and transcriptional markers in the lung. We found both lung-specific as well as systemic effects in immune parameters, metabolites, and lipids. Phytol drove modest changes in lung function and increased splenic CD4 T cell populations. We also conducted multi-omic data integration to better understand early complex pulmonary responses, highlighting a central enhancement of acetylcholine responses and downregulation of palmitic acid connected with conventional flow cytometric assessments of lung, systemic inflammation, and pulmonary function. Our results demonstrate that Ecig exposure not only leads to changes in pulmonary function but also affects systemic immune and metabolic parameters.

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