TY - JOUR
T1 - Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner
AU - Garcia-Arcos, Itsaso
AU - Geraghty, Patrick
AU - Baumlin, Nathalie
AU - Campos, Michael
AU - Dabo, Abdoulaye Jules
AU - Jundi, Bakr
AU - Cummins, Neville
AU - Eden, Edward
AU - Grosche, Astrid
AU - Salathe, Matthias
AU - Foronjy, Robert
N1 - Funding Information:
This work was supported by grants made available to RF (Flight Attendant Medical Research Institute YCSA 24039, CIA 074047 and the US National Institutes of Health 1R01HL098528-05), MS (Flight Attendant Medical Research Institute, CIA 130033 and the James and Esther King Florida Biomedical Research Program grant#5JK02), PG (Flight Attendant Medical Research Institute YCSA 113380) and IG-A (Flight Attendant Medical Research Institute YCSA 13005).
Publisher Copyright:
© 2016 Published by the BMJ Publishing Group Limited.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background: The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. Methods: Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot. Results: Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion. Conclusions: Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use.
AB - Background: The use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells. Methods: Mice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot. Results: Inhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion. Conclusions: Exposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use.
KW - COPD Pathology
KW - COPD ÀÜ Mechanisms
KW - Emphysema
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U2 - 10.1136/thoraxjnl-2015-208039
DO - 10.1136/thoraxjnl-2015-208039
M3 - Article
C2 - 27558745
AN - SCOPUS:84984652751
VL - 71
SP - 1119
EP - 1129
JO - Thorax
JF - Thorax
SN - 0040-6376
IS - 12
ER -