title: Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: 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.
authors: Itsaso
authors: I
authors: Garcia-Arcos
authors: 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.
authors: Patrick
authors: P
authors: Geraghty
authors: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Nathalie
authors: N
authors: Baumlin
authors: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Michael
authors: M
authors: Campos
authors: 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.
authors: Abdoulaye Jules
authors: AJ
authors: Dabo
authors: Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors: Bakr
authors: B
authors: Jundi
authors: Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai St. Luke's Roosevelt Health Sciences Center, New York, New York, USA.
authors: Neville
authors: N
authors: Cummins
authors: Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai St. Luke's Roosevelt Health Sciences Center, New York, New York, USA.
authors: Edward
authors: E
authors: Eden
authors: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Astrid
authors: A
authors: Grosche
authors: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors: Matthias
authors: M
authors: Salathe
authors: 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.
authors: Robert
authors: R
authors: Foronjy
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D066300:Electronic Nicotine Delivery Systems / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride; D008805:Mice, Inbred A; D008875:Middle Aged; D009077:Mucins / Q000096:biosynthesis; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D010447:Peptide Hydrolases / Q000096:biosynthesis; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014029:Tobacco Use Disorder / Q000150:complications*
chemical_list: D016207:Cytokines; D009077:Mucins; D016210:Methacholine Chloride; D009538:Nicotine; D010447:Peptide Hydrolases
keywords: COPD Pathology; COPD ÀÜ Mechanisms; Emphysema