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

Abstract

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.

Electronic Cigarettes: A Pro–Con Review of the Current Literature

“…Notably, this cellular and molecular damage known to drive tumorigenesis was independent of nicotine. Since that publication in 2016, several groups have identified further DNA damaging and DNArepair limiting effects of e-cigarettes, [30][31][32] as well as direct cytotoxic 30,[33][34][35][36] and carcinogenic 31,37 effects of e-cigarettes.…”

“…Human alveolar macrophages and murine bone marrowederived macrophages exposed to e-cigarette aerosols have decreased phagocytosis and efferocytosis. 33,53 Human macrophages differentiated from the monocytic THP-1 cell line exposed to multiple common components of e-liquids (nicotine, propylene glycol, glycerol, and numerous flavorants) show diminished phagocytosis of bacteria after nicotine or flavor exposure, and diminished inflammatory cytokine secretion after exposure to any e-liquid component, including flavors. 54 Neutrophils from the circulation of e-cigarette aerosols as well as those exposed to e-cigarette aerosol extracts were found to have altered neutrophil extracellular trap formation and diminished antimicrobial function.…”

Effects of E-Cigarette Exposure on Prenatal Life and Childhood Respiratory Health: A Review of Current Evidence

“…Interestingly, the authors found that EC can alter bronchial epithelial cell cytokine secretion pathways in a flavor-dependent manner (45). In a more recent study, the flavoring profile of E-liquids has been found to cause bronchial epithelial cell apoptosis, alveolar macrophage phagocytic dysfunction, and to alter airway cytokines, pointing out the issue of regulating flavored E-liquids and the need of more rigorous studies providing clear data on the health impacts of flavored ECs (46). With particular regard to E-liquids mediated effects, two recent studies reported inappropriate activation Ca 2+ signaling pathways which in turn can have a detrimental impact on cell function and survival resulting in a loss of airway epithelial cell viability, and also in inducing pro-inflammatory responses and apoptosis (47,48).…”

A content analysis of the tweets of e‐cigarette proponents in Australia

“…Although marketed as a healthier alternative to traditional cigarettes, 7 e‐cigarettes are not harmless and there are significant health risks associated with their use 8–10 . Short‐term consequences of use include inflammation of lung endothelial cells, airway irritations, oxidative stress and increased heart rate 11–16 . Studies examining long‐term health consequences have linked e‐cigarette use with cell death and increased risk of cardiovascular disease and cancer 17–19 …”

“…[8][9][10] Short-term consequences of use include inflammation of lung endothelial cells, airway irritations, oxidative stress and increased heart rate. [11][12][13][14][15][16] Studies examining long-term health consequences have linked e-cigarette use with cell death and increased risk of cardiovascular disease and cancer. [17][18][19] Australia has some of the most restrictive laws on nicotinecontaining e-cigarettes globally, with the manufacture, sale, or supply of such e-cigarettes without lawful authority prohibited in all Australian states and territories.…”