Abstract Introduction The use of electronic cigarettes (e-cigarettes) has rapidly increased in popularity. Particularly concerning are the high rates of e-cigarette use among youth and young adults. Currently, 4th-generation e-cigarettes in the form of pod-based or disposable devices are the most popular. However, there are limited data on the long-term health effects of e-cigarette vaping, highlighting an need for more research. Our lab has previously demonstrated that 4th-generation devices have immunomodulatory effects following sub-chronic exposures in mice. Here, we seek to determine the impact of chronic e-cigarette exposure on the systemic circulation and lung using a highly physiologic non human primate (NHP) model. Methods Three adolescent male Rhesus macaques (2-3 years old) were exposed to JUUL Virginia Tobacco (59mg/mL nicotinic salts) using a 4-second puff profile with 2 puffs/minute, for 1 hour, 3 days/week, for a total of 25 weeks using an aerosol mask. Bronchoalveolar lavage (BAL) was collected from the left and right lung at baseline and end of exposures. Plasma was collected at baseline, 4 months, and at time of harvest. Soluble immune mediators in plasma at baseline and 6 months were quantified using NUcleic acid Linked Immuno-Sandwich Assay (NULISAseq) Inflammation Panel. A 24-plex multiplex ELISA (MesoScale Discovery) was used for quantifying mediators in BAL. NULISA Protein Quantification (NPQ) units from NULISAseq were log2-transformed and analyzed using a paired t-test with Benjamini-Hochberg correction. Protein concentrations from the 24-plex multiplex ELISA were log2-transformed and compared using a paired t-test as well. Results NHP plasma samples exhibited 50% detection using the human NULISAseq panel. Of the detectable proteins in plasma, E-selectin (suggesting decreased leukocyte adhesion), CD40 ligand (immunodeficiency), CCL5 (periodontitis and thrombocytopenia), IL-5 (CAD and heart failure), and lipocalin-2 (type II diabetes) were found to be significantly decreased after 6 months of e-cigarette exposure, while FGF-21 (obesity, type II diabetes, metabolic syndrome, fatty liver disease) was increased. In BAL, VEGF (IPF, COPD, and ARDS) and MIP-1α (cancer, immunosuppression of T cells) were significantly lowered by e-cigarette exposure. Conclusion Here, we demonstrate that chronic inhalation of e-cigarette aerosols by NHP Rhesus macaques leads to immunomodulatory effects in both the systemic circulation and lung. These changes are highly concerning for the development of serious medical conditions such as diabetes, cardiovascular disease, IPF, COPD, and cancer. Future studies are needed to understand nicotine-dependent and independent mechanisms of immune dysregulation. This abstract is funded by: UC Davis NHP Pilot Award, NIH NHLBI T32 HL166127, NIH NHLBI K24 HL155884, VA Merit I01 BX006447, TRDRP T30IP0965, TRDRP T34IR8251
Perryman et al. (Fri,) studied this question.
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