June 10, 2014

Stanton A. Glantz, PhD

E-cig aerosol has same immediate effect as cigarette smoke on nitric oxide in human lungs

Sara Marini and colleagues just published an interesting paper, "Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide," in Toxicology and Applied Pharmacology that shows that, among smokers, inhaling e-cigarette aerosol has the same effect on the production of exhaled nitric oxide as inhaling a cigarette whether the e-cigarette has nicotine or not.
 
They also provide another confirmation that e-cigarettes produce more and smaller particles than conventional cigaretttes.
 
Nitric oxide (NO) is important because it makes smooth mucle relax and the fact that exposure to e-cigarette aerosol reduces exhaled NO in the lungs may help explain why people who use e-cigarettes have a drop in lung function.  (The fact that smoke reduces NO production in arteries is an important reason that smoking and passive smoking contribute to heart attacks.)
 
The results in this paper are also evidence that the fact that e-cigarettes and cigarettes generate the aerosol differently doesn't matter in terms of this biological effect.
 
Here is the abstract of the paper:
 

The objective of this study was to compare the short-term respiratory effects due to the inhalation of electronic and conventional tobacco cigarette-generated mainstream aerosols through the measurement of the exhaled nitric oxide (eNO). To this purpose, twenty-five smokers were asked to smoke a conventional cigarette and to vape an electronic cigarette (with and without nicotine), and an electronic cigarette without liquid (control session).
 
Electronic and tobacco cigarette mainstream aerosols were characterized in terms of total particle number concentrations and size distributions. On the basis of the measured total particle number concentrations and size distributions, the average particle doses deposited in alveolar and tracheobronchial regions of the lungs for a single 2-s puff were also estimated considering a subject performing resting (sitting) activity.
 
Total particle number concentrations in the mainstream resulted equal to 3.5 ± 0.4 × 109, 5.1 ± 0.1 × 109, and 3.1 ± 0.6 × 109 part. cm− 3 for electronic cigarettes without nicotine, with nicotine, and for conventional cigarettes, respectively. The corresponding alveolar doses for a resting subject were estimated equal to 3.8 × 1010, 5.2 × 1010 and 2.3 × 1010 particles.
 
The mean eNO variations measured after each smoking/vaping session were equal to 3.2 ppb, 2.7 ppb and 2.8 ppb for electronic cigarettes without nicotine, with nicotine, and for conventional cigarettes, respectively; whereas, negligible eNO changes were measured in the control session. Statistical tests performed on eNO data showed statistically significant differences between smoking/vaping sessions and the control session, thus confirming a similar effect on human airways whatever the cigarette smoked/vaped, the nicotine content, and the particle dose received.

Comments

Comment: 

How does this compare to human breath alone without the use of a cigarette or electronic cigarette?

Comment: 

The scientists compared three situations:
 
1. Smoking a conventional cigarette
2. Smoking and nicotine ecigarette
3. Smoking a nicotine-free ecigarette
4. Inhaling through an ecigarette without a liquid cartridge (i.e., breathing normal room air)
 
Conditions 1-3 all reduced exhaled nitric oxide by about the same amount.  There was no effect of condition 4.
 
What this means is that the ultrafine particles in the ecigarette aeorsol (not the nicotine or something special about cigarette smoke aerosol) is what is causing the decrement in lung function.
 
This is a really important finding because it shows, at least for this important biological measure of the effects of using ecigarettes on lungs, they are no different than cigarettes.
 
 

Comment: 

Reflecting on  the blog feedback, I decided to submit this important paper to the FDA as a public comment.  (The tracking number is /sites/g/files/tkssra4661/f/u9/FDA-comment-eNO-1jy-8cms-8qbp.pdf" target="_blank";1jy-8cms-8qbp.)
 
<strong;Evidence that e-cigarette aerosol has the same effects on an important measure of lung function as cigarette smoke undermines the assumption that e-cigarettes are uniformly less risky than conventional cigarettes</strong;
&nbsp;
&nbsp;
Evidence that e-cigarette aerosol has the same effects on an important measure of lung function as cigarette smoke undermines the assumption that e-cigarettes are uniformly less risky than conventional cigarettes
&nbsp;
The paper, "Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide," by Sara Marinia, et al, just published in <em;Toxicology and Applied Pharmacology</em; (Volume 278, Issue 1, 1 July 2014, Pages 9–15), reports important data showing that nicotine e-cigarettes, non-nicotine e-cigarettes, and conventional cigarettes all have similar effects of depression of exhaled nitric oxide (see figure from their paper /sites/g/files/tkssra4661/f/u9/FDA-comment-eNO-1jy-8cms-8qbp.pdf" target="_blank";[available in the PDF of the comment]).
&nbsp;
The authors compared three situations:
&nbsp;
1. Smoking a conventional cigarette
2. Smoking and nicotine e-cigarette
3. Smoking a nicotine-free e-cigarette
4. Inhaling through an ecigarette without a liquid cartridge (i.e., breathing normal room air)
&nbsp;
Conditions 1-3 all reduced exhaled nitric oxide by about the same amount.&nbsp; There was no effect of condition 4.
&nbsp;
What this means is that the ultrafine particles in the e-cigarette aerosol (not the nicotine or something special about cigarette smoke aerosol) is what is causing the decrement in lung function reflected by lower exhaled nitric oxide.
&nbsp;
This is an important finding because it shows, at least for this important biological measure of the effects of using e-cigarettes on lungs, they are no different than cigarettes and so, for this end point, do not pose less risk.&nbsp;
&nbsp;
This finding, which, as the authors point out in their paper, is consistent with earlier studies, demonstrates that <strong;the FDA must be extremely careful about assuming that e-cigarettes uniformly pose less risk than conventional cigarettes.&nbsp; The FDA should not make such an assumption until there is affirmative evidence to support such an assumption.</strong;
&nbsp;
Stanton A. Glantz, PhD
Professor and Director

Comment: 

FeNo is a measure of airway inflammation[1][2], nothing more. It does not signify increased risk, harm, or any long term effect.
It indicates that, as is already well known, propylene glycol causes mild airway irritation. Given that use of ecigs has, in a small study, been associated with harm reversal in asthma sufferers[3], it would seem that the effect is transitory, and not of clinical significance, even in populations with existing risk factors.
Nothing more.
Claiming otherwise is disingenuous at best, and would generally be considered to be an out and out lie
[1] Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care, http://www.ctajournal.com/content/3/1/37" title="http://www.ctajournal.com/content/3/1/37";http://www.ctajournal.com/cont...
[2] Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naïve atopic asthmatic children, http://www.ncbi.nlm.nih.gov/pubmed/15584636" title="http://www.ncbi.nlm.nih.gov/pubmed/15584636";http://www.ncbi.nlm.nih.gov...
[3]Effect of Smoking Abstinence and Reduction in Asthmatic Smokers Switching to Electronic Cigarettes: Evidence for Harm Reversal, http://www.mdpi.com/1660-4601/11/5/4965" title="http://www.mdpi.com/1660-4601/11/5/4965";http://www.mdpi.com/1660-4601/1...

Comment: 

... there is a direct biological effect that is the same for cigs and ecigs.
&nbsp;
Propylene gycol is causing the same kind of airway irritation that smoking does.
&nbsp;
There is a short-term clinical effect, too.&nbsp; Other studies have found measurable drops in air flow, which is just what you would expect.
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