Thursday, July 25, 2013

Anti-Smoking Researcher Misleads Public with Invalid Comparison of E-Cigs and Nicotine Inhaler: Correct Analysis Shows that Nicotine Inhalers Have Higher Amounts of Six Carcinogens

On his tobacco blog last week, Dr. Stan Glantz argued that nicotine inhalers are safer than electronic cigarettes as a harm reduction product based on a comparison he made between the amounts of several carcinogens in e-cigarette cartridges and nicotine inhaler cartridges. Actually, the comparison was between levels of these chemicals in the vapor produced from these cartridges. The data were taken from a paper by Goniewicz et al. that reported levels of various constituents of e-cigarette vapor and used a nicotine inhaler as a reference product.

Here is the analysis that Dr. Glantz reports:

"The unsigned comment is quoting the abstract of the paper by Goniewicz, et al. that I used to get compounds to compare with the Proposition 65 list.  Their paper also compared the levels of these compounds with a nicotine inhaler (the "reference" product" they refer to in the abstract, but did not fully develop that comparison.

Here are the results computed from Table 3 in their paper:

                                   ecig   inhaler   ratio
Formaldehyde        28.2      2.0         14
Acetaldehyde            7.4       1.1          7
Acrolein                    11.5      ND          --
o-methylbenzyne      3.9       0.7         6
Toluene                      0.8       ND         --
p,m-xylene                 0.1       ND         --
NNN                            1.5       ND         --
NNK                             6.6      ND         --
Cadmium                  0.09    0.03        3
Nickel                         0.19    0.19        1
Lead                           0.09    0.04        2
ND=not detected

Looked at this way, an e-cig delivers 14 times as much formaldehyde, 7 times as much actaldehyde, 6 times as much o-methylbenzene, 3 times as much cadmium and twice as much lead as a nicotine inhaler, as well as acrolein, toulene, p,m-xylene, NNN and NNK, which were not detected in the "reference device."

Based on these comparisons, one could use the data in this paper to conclude that nicotine inhalers would be a safer approach to delivering nicotine in a harm reduction strategy than e-cigarettes."

The Rest of the Story

The only problem with this analysis is that it is wrong.

The analysis is essentially comparing the amount of these chemicals produced by one cartridge of an electronic cigarette versus one cartridge of a nicotine inhaler.

Sound like a fair comparison? Comparing apples to apples?

Well, no.

While 150 puffs is the approximate dose of vapor that an electronic cigarette user inhales per day (about one cartridge - depending on the brand), a typical nicotine inhaler user will go through about 16 cartridges per day. Obviously, these figures vary depending on the individual, but it is not unreasonable to assume that a typical vaper would take 150 puffs per day, while a nicotine inhaler user might use 16 cartridges per day.

Since what we are interested in is the difference in toxicant exposure, we must take the number of cartridges used per day into our analysis. What we want to estimate and compare is the total daily exposure to these various chemicals.

So here is Dr. Glantz's table reproduced correctly to represent a comparison of daily carcinogen intake rather than intake from one cartridge:

                                   ecig   inhaler   ratio
Formaldehyde        28.2      32.0         0.9
Acetaldehyde            7.4       17.6          0.4
Acrolein                    11.5      ND          --
o-methylbenzyne      3.9       11.2         0.3
Toluene                      0.8       ND         --
p,m-xylene                 0.1       ND         --
NNN                            1.5       ND         --
NNK                             6.6      ND         --
Cadmium                  0.09    0.48        0.2
Nickel                         0.19    3.0        0.1
Lead                           0.09    0.64        0.1
ND=not detected

You can see that in contrast to what Dr. Glantz reported, the estimated daily exposure to six carcinogens is substantially higher for use of a nicotine inhaler compared to use of electronic cigarettes, based on the very same data that he believes is valid. As you can see, this changes the conclusion quite a bit.

To put it another way, here is the same table showing the ratio of daily exposure to chemicals from inhalers compared to e-cigarettes:

                               inhaler   ecig   ratio
Formaldehyde        32.0      28.2         1.1
Acetaldehyde            17.6       7.4          2.4
Acrolein                    ND      11.5          --
o-methylbenzyne      11.2       3.9         2.9
Toluene                      ND       0.8         --
p,m-xylene                 ND       0.1         --
NNN                            ND       1.5         --
NNK                             ND      6.6         --
Cadmium                  0.48    0.09        5.3
Nickel                         3.0    0.19        15.8
Lead                           0.64    0.09       7.1
ND=not detected
The rest of the story, then, is that use of a nicotine inhaler actually exposes users to higher levels of six different carcinogens than electronic cigarettes. Exposure to nickel is nearly 16 times higher. Exposure to lead is seven times higher. Exposure to cadmium is five times higher. And exposure to o-methylbenzene is three times higher.

Now unlike Dr. Glantz, I don't believe that these data are anywhere near sufficient to draw any conclusion about whether e-cigarettes would be safer or more appropriate as a harm reduction tool than nicotine inhalers. The point of this analysis is simply to show that when one is biased against a particular product, one loses the scientific objectivity and broader view that is necessary to provide a valid analysis.

So to be clear, I do not conclude from this analysis that e-cigarettes are safer than nicotine inhalers or more appropriate as a harm reduction tool. However, I do conclude that Dr. Glantz's analysis is invalid and misleading, and that based on the available data, it appears that electronic cigarettes are in the same relative vicinity as nicotine replacement products in terms of carcinogenic risk. In other words, they appear to be in the same ballpark.

In terms of likely cancer risk, then, we are not talking about the difference between Yankee Stadium and Fenway Park. We are talking about the difference between Fenway Park in the daytime and Fenway Park in the evening. (The Sox are 19-11 in day games and 42-30 in night games so I think I'm on solid ground, although I don't have the home/away splits.)

Four important things to note:

First, the analysis is obviously dependent on the assumptions regarding the number of puffs a vaper takes a day and the number of cartridges a nicotine inhaler user goes through per day. The point of this analysis is not to produce a precise estimate of exposure differences. It is merely intended to show that the original analysis is not tenable because the assumptions are grossly off. Nevertheless, my assumptions appear to be reasonable. For a medium smoker, 150 puffs a day is not unreasonable. And it is well-documented that many nicotine inhaler users go through as many as 20 cartridges per day.

Second, most people do not use nicotine inhalers for long periods of time (usually, only for a period of months). The duration of use is of course important in determining risk. However, since Dr. Glantz was comparing the two products for use in "harm reduction," we might as well go ahead and make that comparison.

Third, the relative safety difference between the two products is only a small part of the analysis of which would be more appropriate for harm reduction. The effectiveness of the products are also an important consideration. Nicotine inhalers are quite ineffective. The promise of electronic cigarettes is that they address not only the pharmacological aspects of the smoking addiction, but also the behavioral, psychological, and social aspects.

Finally, readers should not make too much out of the finding that e-cigarette cartridges had an average of 8.1 micrograms of tobacco-specific nitrosamines (NNN and NNK), while the nicotine inhaler did not have detectable levels. Why? Because it is well-documented that two other forms of NRT - nicotine patches and gum - do have detectable levels of NNN and NNK and these levels are comparable to those in electronic cigarettes. For example, one study found tobacco-specific nitrosamine levels of 8.0 ng in the nicotine patch compared to 8.2 ng/g in electronic cigarettes.

To conclude, I think there is much room for debate and discussion regarding the appropriate role for electronic cigarettes in tobacco control. Dissenting opinions from my own are valuable and necessary to ensure that the proper consideration is given to both the advantages and potential disadvantages of these products. However, we dearly need balanced and science-based perspectives that are as unbiased as possible. Pre-determined conclusions that lead researchers to misrepresent the science is not valuable to the process of formulating the policy that will best advance the interests of the public's health.

Remember, we're trying to save the lives of smokers, not of anti-smoking groups.

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