E-cigarettes and health risks: more to the flavour than just the name

Rationale: The growing interest in regulating flavoured E-liquids must incorporate understanding of the "flavouring profile" of each E-liquid - which flavourants (flavouring chemicals) are present and at what concentrations not just focussing on the flavour on the label. Methods: We investigated the flavouring profile of 10 different flavoured E-liquids. We assessed bronchial epithelial cell viability and apoptosis, phagocytosis of bacteria and apoptotic cells by macrophages after exposure to E-cigarette vapour extract (EVE). And validated in normal human bronchial epithelial cells (NHBE) and alveolar macrophages (AMs) from healthy donors. We also assessed cytokine release and validated in the saliva from E-cigarette users. Results: Increased necrosis/apoptosis (16.1-64.5% apoptosis) in 16HBE cells was flavour dependent, and NHBEs showed an increased susceptibility to flavours. In THP-1 differentiated macrophages phagocytosis was also flavour dependent, with alveolar macrophages (AM) also showing increased susceptibility to flavours. Furthermore, Banana and Chocolate were shown to reduce surface expression of phagocytic target recognition receptors on alveolar macrophages. Banana and Chocolate increased IL-8 secretion by NHBE, whilst all 4 flavours reduced AM IL-1β secretion which was also reduced in the saliva of E-cigarette users compared with healthy controls. Flavourant profiles of E-liquids varied from simple 2 compound mixtures to complex mixtures containing over a dozen flavourants. E-liquids with high benzene content, complex flavouring profiles, high chemical concentration had the greatest impacts. Conclusions: The flavourant profile of E-liquids is key to disruption of the airway status quo by increasing bronchial epithelial cell apoptosis, causing alveolar macrophage phagocytic dysfunction and altering airway cytokines.