Nicotine promotes e-cigarette vapour-induced lung inflammation and structural alterations

BACKGROUND: Electronic cigarette (e-cigarette) vapour is gaining popularity as an alternative to tobacco smoking and can induce acute lung injury. However, the specific role of nicotine in e-cigarette vapour and its long-term effects on the airways, lung parenchyma and vasculature remain unclear. RESULTS: In vitro exposure to nicotine-containing e-cigarette vapour extract (ECVE) or to nicotine-free e-cigarette vapour extract (NF ECVE) induced changes in gene expression of epithelial cells and pulmonary arterial smooth muscle cells (PASMCs), but ECVE in particular caused functional alterations (e.g. a decrease in human and mouse PASMC proliferation by 29.3±5.3% and 44.3±8.4%, respectively). Additionally, acute inhalation of nicotine-containing e-cigarette vapour (ECV) but not nicotine-free e-cigarette vapour (NF ECV) increased pulmonary endothelial permeability in isolated lungs. Long-term in vivo exposure of mice to ECV for 8 months significantly increased the number of inflammatory cells, in particular lymphocytes, compared to control and NF ECV in the bronchoalveolar fluid (BALF) (ECV: 853.4±150.8 cells·mL(-1); control: 37.0±21.1 cells·mL(-1); NF ECV: 198.6±94.9 cells·mL(-1)) and in lung tissue (ECV: 25.7±3.3 cells·mm(-3); control: 4.8±1.1 cells·mm(-3); NF ECV: 14.1±2.2 cells·mm(-3)). BALF cytokines were predominantly increased by ECV. Moreover, ECV caused significant changes in lung structure and function (e.g. increase in airspace by 17.5±1.4% compared to control), similar to mild tobacco smoke-induced alterations, which also could be detected in the NF ECV group, albeit to a lesser degree. In contrast, the pulmonary vasculature was not significantly affected by ECV or NF ECV. CONCLUSIONS: NF ECV components induce cell type-specific effects and mild pulmonary alterations, while inclusion of nicotine induces significant endothelial damage, inflammation and parenchymal alterations.

• Roxlau, E. T.
• Pak, O.
• Hadzic, S.
• Garcia-Castro, C. F.
• Gredic, M.
• Wu, C. Y.
• Schäffer, J.
• Selvakumar, B.
• Pichl, A.
• Spiegelberg, D.
• Deutscher, J.
• Bednorz, M.
• Schäfer, K.
• Kraut, S.
• Kosanovic, D.
• Zeidan, E. M.
• Kojonazarov, B.
• Herold, S.
• Strielkov, I.
• Guenther, A.
• Wilhelm, J.
• Khalifa, M. M. A.
• Taye, A.
• Brandes, R. P.
• Hecker, M.
• Grimminger, F.
• Ghofrani, H. A.
• Schermuly, R. T.
• Seeger, W.
• Sommer, N.
• Weissmann, N.