June 3, 2015

Stanton A. Glantz, PhD

How nicotine and e-cigs (even without nicotine) damage lung cells (which helps explain reduced lung function)

An important paper (Endothelial disruptive pro-inflammatory effects of nicotine and e-cigarette vapor exposures) has just been published in American Journal of Physiology: Lung Cellular and Molecular Physiology that carefully dissects the effects on nicotine and e-cigarette aerosol (both with and without nicotine) on the cells that line the air sacks in the lung.  What the authors very carefully show is that nicotine, whether from cigarettes or e-cigarettes, causes a dose-dependent disruption of the functioning of these cells. 
 
The authors do a series of elegant experiments (with both isolated rat lung cells and whole rats) and drill right down to the cellular and molecular pathways through which nicotine damages lung cells in ways that lead to clinical disease.  This result is particularly important in light of the common rhetoric that comes out of many harm reduction advocates (and, occasionally, the FDA) that it is the smoke, not the nicotine, that is the problem with tobacco use.
 
Another important result in this paper is that nicotine free e-cigarette aerosol (and the authors carefully verified that there was actually not any nicotine in the nicotine-free e-cigarette liquid) had many of the same effects as the nicotine-containing e-cigarette aerosol.  While they did not nail down precisely what element or elements of the aerosol were causing the effect, they suggested that it was due to the acrolein produced by the e-cigarettes.
 
Here is the bottom line: “These results suggest that soluble components of e-Cig, including nicotine, case dose-dependent loss of lung endothelial barrier function, associated with oxidative stress and brisk inflammation.”
 
These results are consistent with, and help explain, the clinical observations that e-cigarette use is followed by an immediate drop in lung function comparable to that seen in cigarette smokers.

Comments

Comment: 

 
This is an interesting review of the paper you cite: http://rightwit.com/2015/05/e-cigarette-nicotine-free-vapor-still-danger... , which links to a very thought provoking article about Acrolein here: http://www.pnas.org/content/103/42/15404.full.pdf+html";http://www.pnas.... and this particular carbonyl/aldehyde’s links with: lung cancer. This paper by Bekki et al http://www.mdpi.com/1660-4601/11/11/11192/htm";http://www.mdpi.com/1660-...   , Externally Edited by Dr Konstantinos Farsalinos, states the following regarding levels of acrolein (and other carbonyls) found in some e-cigarettes:
“extremely high concentrations of these carbonyl compounds are generated, and may contribute to various health effects. Suppliers, risk management organizations, and users of e-cigarettes should be aware of this phenomenon.”
This paper http://www.ncbi.nlm.nih.gov/pubmed/24832759";http://www.ncbi.nlm.nih.gov... including input from Maciej Gonerwicz, confirms these findings, and states that levels of carbonyls in e-cigarettes can be in the range of tobacco smoke.
Other significant recent papers regarding airway inflammation and ENDS aerosol include these from the recently presented at the American Thoracic Society Conference:
http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2015.191.1_...
http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2015.191.1_...
This paper http://www.fasebj.org/content/29/1_Supplement/LB631.short";http://www.fa... concludes: “eCV induced autophagy impairment and aggresome-formation activates apoptosis/senescence suggesting its potential role in COPD-emphysema pathogenesis.”
This paper http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317176/";http://www.ncbi.nl... concludes, amongst other things: “Cigarette smoke contains 1014 free radicals per puff [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317176/#pone.0116861.ref013..., and is a potent source of oxidative stress. Many free radicals are produced during combustion of tobacco, and since E-cigs do not contain any combustion products, it has been assumed that E-cigs will have very low levels of free radicals. We determined that E-cig vapor contains 7x1011 free radicals per puff and elicits a significant increase in oxidative stress. While this concentration is several orders of magnitude lower than in cigarette smoke, it is nonetheless a substantial number of free radicals that could be potentially toxic to cells.”
There is therefore a very concerning body of evidence emerging with regard to ENDS and links to airway inflammation, emphysema and even lung cancer, as here: http://clincancerres.aacrjournals.org/content/20/2_Supplement/B16.abstra... .
David Bareham

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