Systemic biomarkers in electronic cigarette users: implications for noninvasive assessment of vaping-associated pulmonary injuries

Background: Electronic cigarettes (e-cigs) were introduced as electronic nicotine delivery systems, and have become very popular in the USA and globally. There is a paucity of data on systemic injury biomarkers of vaping in e-cig users that can be used as a noninvasive assessment of vaping-associated lung injuries. We hypothesised that characterisation of systemic biomarkers of inflammation, anti-inflammatory, oxidative stress, vascular and lipid mediators, growth factors, and extracellular matrix breakdown may provide information regarding the toxicity of vaping in e-cig users. Methods: We collected various biological fluids, i.e. plasma, urine, saliva and exhaled breath condensate (EBC), measured pulmonary function and vaping characteristics, and assessed various biomarkers in e-cig users and nonusers. Results: The plasma samples of e-cig users showed a significant increase in biomarkers of inflammation (interleukin (IL)-1 beta, IL-6, IL-8, IL-13, interferon (IFN)-., matrix metalloproteinase-9, intercellular cell adhesion molecule-1) and extracellular matrix breakdown (desmosine), and decreased pro-resolving lipid mediators (resolvin D-1 and resolvin D-2). There was a significant increase in growth factor (endothelial growth factor, vascular endothelial growth factor, beta-nerve growth factor, platelet-derived growth factor-AA, stem cell factor, hepatocyte growth factor and placental growth factor) levels in plasma of e-cig users versus nonusers. E-cig users showed a significant increase in levels of inflammatory biomarker IFN-gamma, oxidative stress biomarker 8-isoprostane and oxidative DNA damage biomarker 8-oxo-dG in urine samples, and of inflammatory biomarker IL-1 beta in saliva samples. EBC showed a slight increase in levels of triglycerides and 8-isoprostane in e-cig users compared with normal nonusers. Conclusion: E-cig users have increased levels of biomarkers of inflammation and oxidative stress, reduced proresolving anti-inflammatory mediators, and endothelial dysfunction, which may act as risk factors for increasing susceptibility to systemic diseases. The identified noninvasive biomarkers can be used for determining e-cig vaping-associated lung injuries, and for regulatory and diagnostic aspects of vaping in humans.