SESSION TITLE: Lung Pathology Posters
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM
PURPOSE: Use of alternative nicotine delivery devices such as electronic cigarettes (e-cig) has increased largely due to the perceived safety profile and assumed absence of deleterious chemicals present in cigarette smoke. Little is known regarding the safety of these products and their effects on lung health. Here, we show that e-cigarette vapor inhibits ion transport through the CFTR Cl- channel, and contains elevated levels of acrolein; both of which are known to impair mucociliary clearance. Additionally, we evaluate the effects of unburned e-cigarette liquid on ion transport.
METHODS: Calu-3 airway epithelial cells were cultured at air-liquid interface until terminal differentiation and exposed to a popular e-cig blend (Red Oak Domestic, ROD) or its vehicle control (vegetable glycerin, VG), in burned and unburned conditions. Ion transport was measured via short-circuit current (Isc) in modified Ussing chambers with sequential addition of amiloride (100 μm), chloride gradient, forskolin (20 μm), CFTRInh-172 (10 μm), ATP (100 μm), and bumetanide (100 μm). Unburned liquid was added between forskolin and CFTRInh-172 in logarithmic doses (1, 3, 10, 30, 100, 300μL). Acrolein content was assessed using mass spectrometry, and cytotoxicity with LDH enzyme activity.
RESULTS: Compared to controls, the addition of 1, 10 and 300μL of ROD liquid significantly reduced CFTR-dependent Isc (p < 0.05), as did exposure to 30 minutes of ROD vapor. Similarly, the addition of 10 and 300μL of VG reduced CFTR-dependent Isc (p < 0.05). ATP-stimulated and CFTR-independent Isc were also reduced by unburned ROD and VG liquids (p < 0.05, p < 0.005), which was confirmed by a decrease in bumetanide-inhibitable current (p < 0.05, p < 0.005), indicating a reduction in total basolateral Cl- exchange in response to ROD or VG liquid exposure. Acrolein content in PBS exposed to burned ROD was elevated compared to air control (p < 0.0005).
CONCLUSIONS: Vapor generated from commercial e-cig blend contains elevated levels of acrolein and inhibits CFTR-dependent ion transport in airway epithelial cells. These effects on ion transport were not due to cellular toxicity, as revealed by LDH assay. Exposure to unburned e-cig liquid, as well as a popular flavor vehicle, also inhibit ion transport necessary for proper mucociliary clearance.
CLINICAL IMPLICATIONS: Exposure to e-cigarette liquid and vapor inhibits CFTR ion transport, suggesting negative implications for airway physiology and mucociliary clearance, regardless of burning.
DISCLOSURE: The following authors have nothing to disclose: Matthew Fain, Vamsee Raju, Vivian Lin, Li Ping Tang, Courtney Fernandez, Marina Mazur, James Blalock, Patricia Jackson, Steve Rowe
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