Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner
Authors: Patrick Geraghty
Neville Cummins
Matthias Salathe
Itsaso Garcia-Arcos
Michael Campos
Nathalie Baumlin
Astrid Grosche
Robert Foronjy
Abdoulaye Jules Dabo
Edward Eden
Bakr Jundi
Journal: Thorax (2016)
Discipline: CLINICAL MEDICINE
Keywords: COPD Pathology; COPD ÀÜ Mechanisms; Emphysema.
Affiliations: Division of Pulmonary and Critical Care Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA., Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, USA., Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA., Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland., Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai St. Luke's Roosevelt Health Sciences Center, New York, New York, USA.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Responding to Foronjy, it has been shown that there is a threshold effect for nicotine pulmonary effects. Phillips and colleagues note that administering an otherwise harmless dose of nicotine over a very short duration will cause pulmonary damage, even via non-inhalation routes: *** Absence of pulmonary changes in this study is in contrast to the reported effects of subchronic administration of nicotine via non-inhalation routes in which the entire daily dose (usually 20% of the inhaled daily dose, 13.6 mg kg) was delivered as a single bolus with very high transient concentrations, which could explain the observed toxic effects *** Phillips et al.  Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Spragueu2013Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology. Inhalation Toxicology 2015 https: scholar.google.com scholar?cluster=8159874997512506110 Indeed, this study exposed mice to the nicotine equivalent of about 200 cigarettes over a single hour daily. Zvi Herzig ,