Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

Abstract

BackgroundThe 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.MethodsMice 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.ResultsInhalation 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.ConclusionsExposure 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.

Nicotine-Induced Airway Smooth Muscle Cell Proliferation Involves TRPC6-Dependent Calcium Influx Via α7 nAChR

“…Traditionally, nicotine has been studied as the addictive component in cigarettes, but increasing evidence has indicated that nicotine is also a key factor in the initiation and progression of COPD. Nicotine hinders the hydration of mucus, promotes cell proliferation by causing calcium influx in ASMCs, induces pro-inflammatory dendritic cell responses, and blocks neutrophil apoptosis [31]. Despite the absence of a clear understanding of nicotine-induced health risk, some manufacturers have suggested that using nicotine can help someone who extensively smoke quit their smoking habit, which is widely known to be hazardous to health.…”

Should e-cigarette use be permitted in smoke-free public places? No

“…Recent reports of rapid-onset changes in aortic stiffness after exposure to vape,8 of mice exposed to vape with nicotine developing features of chronic obstructive pulmonary disease9 and a 2014 report of increases in fractional exhaled nitric monoxide (FeNo),5 a marker of eosinophilic airway inflammation, following vaping are examples of possibly vanguard research findings that may prove important.…”

“…While documented indoor concentrations of exhaled vape constituents are often lower than those arising from cigarettes,9 real world scenarios can involve significant exposure. Scenes from ‘vapecons’ abound on YouTube,11 where large numbers of ENDS users participate in ‘clouding’ contests, show worst case scenarios (eg, http://www.youtube.com/watch?v=4NPe3rAYG_Q&t=0m46s).…”

Review of the British Thoracic Society Winter Meeting 2016, 7–9 December, London, UK

“…This suggests that targeting autoimmunity in at-risk patients could be a novel strategy to prevent ILD 8. Professor Foronjy (New York, USA) demonstrated that inhaled nicotine e-cigarette solution leads to airway inflammation and airspace enlargement in mice, suggesting that in addition to being the addictive component of cigarettes, nicotine also plays a key role in the initiation and progression of COPD 9. Finally, Dr Melissa McDonnell (Newcastle) discussed different bronchiectasis severity measures in seven European cohorts, and showed that the Bronchiectasis Severity Index was superior at predicting clinically useful outcomes such as hospitalisation, exacerbations, lung function decline and quality of life 10…”