Opposition to e-cigarettes - a health risk analysis

[rolygate]

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Some notes on pharmaceutical industry opposition to electronic cigarettes, and an analysis of health risks from e-cigarette use

The real opponent to e-cigarettes is the pharmaceutical industry, not government (or the tobacco industry), but not because of the threat to NRT sales. This does come into it, but it's only a small part of the issue. NRT and quit-smoking drugs are a $3bn annual global market, certainly - but the sales of drugs and therapies for the treatment of sick smokers makes the NRT market look like chump change.

Sales of chemotherapy drugs, COPD drugs, cardiac drugs, vascular drugs, plus other therapies for ill smokers, plus the hospitalization / healthcare income with which pharma is also associated, are likely to be in the $100bn a year range, if not higher (that's one hundred billion dollars a year). This is where the real threat to pharma is, because the growth in e-cigarette use has a very real chance of cutting all those income streams by at least 50%.

Proven stats: Snus
The best guide to what can be expected is the Sweden scenario: the free availability and popularity of Snus there has reduced the number of smokers by about 45% (11% of Swedes smoke compared to about 20% in comparable countries), and smoking-related deaths have fallen in parallel. Sweden has the lowest male lung cancer and oral cancer rate in Europe - even though Snus is an oral tobacco product, it has had most of the carcinogens removed by processing.

They have the lowest smoking-related mortality rate in the developed world by a wide margin [1].

Since ecigs are far more popular than Snus where both can be sold together, it is not unreasonable to guess that ecig takeup in some countries will be even higher than Snus in Sweden. Currently it is thought that 21% use Snus and 11% smoke, in Sweden - which gives some sort of guide to what we can expect here; ecig uptake here is likely to be higher than this, eventually (though it has taken decades for Sweden to reach these numbers).

The pharmaceutical industry is desperate to stop the Sweden scenario spreading to other countries, as their income in Sweden is so poor compared to that in other developed countries: Snus users don't get sick and die except as a result of their previous smoking habit, and therefore don't need the hugely-profitable treatment drugs; and far fewer people buy NRTs there, since they have something that works much better.

There are more than 150 clinical trials and surveys of Snus in Sweden, over more than 25 years, with tens of thousands of subjects. There are also giant-scale meta-analyses of the trials. The data available is on such a massive scale, compared to the usual situation with clinical trials and surveys surrounding a topic, that it cannot be discounted or negated (or perverted). It shows that:

1. A Snus user can expect the same health outcomes as a non-smoker (a 'non-smoker' = an ex-smoker in medical terminology).
2. Smokers who totally quit or switch to Snus have the same health outcomes - there is no statistically significant difference in outcomes.
3. Snus does not elevate risk for any disease.

A small increase in risk for stroke is demonstrated, but this is not of significant value. Although one or two trials have shown a small increase in risk for pancreatic cancer, a meta-analysis of the 89 trials where possible confounders had most reliably been removed showed no risk elevation.

Extremely low risks are present and cannot be denied, although these are not statistically significant never mind clinically significant:

• A cigarette smoker can expect an average reduction in lifespan of around 8 years (medics do not agree on this, but do agree that a reduction of somewhere between 6 and 10 years is likely).
• Snus consumers can expect an average reduction in lifespan of around 4 weeks (the range is demonstrated to be between 2 weeks and 8 weeks).

The Snus risk seems similar to that of drinking coffee.

However, it is unnecessary to research something when there are facts available. Clinical trials, no matter how many of them there are, can only provide evidence - they cannot prove something. Reliable national statistics though, can be regarded as proof, since they are a fact. Sweden has far less people dying from smoking than anywhere else in the developed world, which is why it is sometimes called the Swedish Miracle. Sweden has about half the smoking-related death rate of the EU average, and all statistics related to morbidity and mortality associated with smoking are significantly reduced in comparison with those in comparable countries. Sweden has the lowest figures in the EU for any disease associated with smoking. Allowing for the two-decade timelag in the rise or fall of disease stats resulting from increased or reduced smoking or tobacco use, the reduction in death and illness is equal to the reduction in the number of smokers (and by implication the number who are Snus consumers).

Sweden is a disaster for pharma since much lower quantities of treatment drugs are required there, and they are desperate to stop anything like it happening elsewhere.

Nicotine risk
Because the long-term consumption of tobacco without smoke is proven (in certain circumstances) to have no significant health risk, it is also assumed this applies to nicotine - rightly or wrongly, although this is more of a technical/logic issue than anything else.

Pharmaceutical companies want NRTs to be licensed for long-term use, because this addresses the twin benefits of more profits and better performance. As there is no data anywhere for long-term nicotine consumption apart from the Snus data (for which, as we have seen, there is a data mountain), it was used recently in the UK when applications to extend the NRT usage period were lodged. The Snus data was presented as evidence that long-term nicotine use can safely be regarded as having negligible risk, and as a result the long-term NRT usage application was successful.

Indeed, the UK medical licensing authority, the MHRA, which is the local equivalent of the FDA, has described nicotine as, "a very safe drug" - almost certainly as a result of the Snus experience, since there is no other source of data of this type or on this scale. It may well be true that their motives for doing this are to accommodate the pharmaceutical industry; but on the other hand it does tend to legitimize the Snus data at the same time. There is a small amount of data over a shorter timescale for long-term NRT users, but nothing that compares with the Snus data in scale or time.

As a side note, we occasionally see new trials of some aspect of nicotine being published. It needs to be pointed out that such trials are irrelevant if they discuss the health aspects or relative safety of nicotine consumption, since we already have a data mountain on this topic along with population-level proof of the trials' veracity in an isolated population over several decades, where nicotine-influenced morbidity and mortality has been minutely analysed. In fact one might say that 'new trials' of nicotine are among the most pointless that could be funded since we already know the answers.

There is only one aspect that warrants further investigation: an analysis of morbidity and mortality in a very large cohort consuming pure nicotine over three decades; such as could be provided by an electronic cigarette user population, for example.

Snus vs ecigs
As regards the relative risks of Snus and ecigs, there are numerous professors of medicine / world-renowned epidemiologists / heads of public health departments / experts in tobacco-related disease and mortality [2], who say that the risk for a Snus user and that of an ecig user, provided they switch completely and are not dual-users with tobacco cigarettes, is around 1% or less than that of smoking. This is proven for Snus but not proven for ecigs. Some say ecigs will be safer as they only supply nicotine and not the other components of tobacco. Some agree but say that, due to the inhalation of foreign materials, the relative advantages disappear.

The popular Russian roulette analogy
Some like to use a Russian roulette analogy to describe the risks of smoking. For a comparison between smoking and vaping, it can be used by adding many more revolvers, all unloaded, to account for the huge reduction in risk with e-cigarettes.

If the choice is between an approximate 33% risk of death from smoking (which by the way cannot be agreed by the medical profession since opinions vary anywhere between 20% and 50%, both of which are probably untenable positions); and ecigarette use, which is suggested as having somewhere between 1% and 0.0001% of the risk of smoking, then you might put it like this:

• Choice A (smoking) is Russian roulette with a revolver with 2 chambers out of 6 loaded.
• Choice B (vaping) is Russian roulette with a selection of revolvers (about 17), only one of which has 1 chamber loaded.

Possible disease vectors for e-cigarettes
Some people will die as a result of vaping because to say otherwise is not a realistic position to take. If 10 million smokers switch to electronic cigarettes, some will die as a result. This would be the case if they switched to eating doughnuts, or indeed any other consumption activity. The question is, by what form of illness. Here is a possible list:

1. Persons with pre-existing serious lung disease caused by smoking, such as Stage 4 COPD or emphysema. These persons should quit inhalation totally as, particularly for emphysema patients, there is a greatly-increased risk of pneumonia. Continuation of any form of inhalation of extraneous materials is in essence suicide, or death from smoking; not death caused by vaping. Snus is a better choice for such persons. If inhalation of ecig vapor contributes to earlier death (perhaps by assisting the predisposition to pneumonia that emphysema patients have), the ecig cannot be stated to be the cause of death [6].

2. Persons with pre-existing serious heart disease as a result of smoking, who should no longer consume nicotine in any more than dietary quantities. Continuation of excessive nicotine consumption is in essence suicide, or death from smoking; not death caused by vaping. If use of an ecig with large amounts of nicotine contributes to earlier death (perhaps by negatively affecting cardiac health), the ecig cannot be stated to be the cause of death.

3. Persons with lung issues, who react with unusual severity to inhalation of certain materials to which they have extreme intolerance, and who already have compromised lungs from smoking. This is going to be rare, but will occur [3].

4. Persons who are unfortunate victims of toxic contaminants. Again this will be rare, but is a statistical probability, especially since we are the guinea pigs where the inhalation of flavorings is concerned.

5. Persons who cannot tolerate long-term consumption of large quantities of nicotine without issue. The number in this group will not be high - but it will exist. Some may have a genetic predisposition to vascular disease for example: a history of family members dying early from stroke or similar. It may be that a very small number of persons could develop a-fib or related problems, as a result of excessive consumption, and this will have consequences for a small number of individuals.

It should be pointed out that, essentially, some people have to die as a result of any/every activity, so it's just a question of looking at what the factors involved might be. One possible assessment of the risk of vaping is that it will turn out to be around 0.01 to 0.001% that of smoking. One professor of medicine described the likely lifetime risk of vaping as 0.3 on a scale where smoking is 100. For some individuals the risk will be much higher than this; for some, much lower. People are very different.

Most importantly, the individual can also manage their own risk profile optimally, by careful consumer purchase choices.

As an example of how different people can be, some get nic OD symptoms if they overdo it on 6mg eliquid (0.6% strength), and cannot tolerate 12mg (1.2%) at all; some get no symptoms whatsoever when using 60mg liquid (6%). This shows a factor 10 difference in tolerance to nicotine, and is probably typical of the variation between individuals in many ways. This tenfold difference in tolerance to nicotine has been demonstrated in ECF members (and probably nowhere else), so we might expect other interesting features of individual tolerances or reactions to also be reported here first.

What the future holds
The FDA is, for all practical purposes, the legal arm of the pharmaceutical industry. Their agenda is to ban e-cigarettes, or if this is not possible, to restrict them in order to reduce sales, by the use of regulations designed to reduce availability/efficiency/desirability. If such regulations prove possible to introduce, sales will be restricted or reduced, thus protecting pharmaceutical industry income [4].

A ban has been legally rejected, so we can expect an assault on any and every feature that makes ecigs an attractive or easily-purchased alternative to smoking. The areas we might see attempted restrictions in are: availability of flavors, availability of liquid refills, legality of web sales, and even perhaps an attempt to remove any design not on sale by late 2006. Whether or not the FDA will be able to enforce such restrictions is not clear at this time, but they will certainly look at these options because that is the pharmaceutical industry's best option: strangle e-cigarette sales by increasingly tough regulations. It's either that or see a 50% or even 60% cut in several of their important income streams due to smokers not becoming sick; a negative impact of tens of billions of dollars. To imagine pharma will stand by and let that happen is not realistic.

They are also likely to receive the support of elements within the electronic cigarette industry who can survive under the toughest regulatory climate, since that will restrict or remove opponents; this is simply a basic commercial tactic, employed most successfully, normally, by the pharmaceutical industry.

The US convenience store trade reports that cigarette sales are falling by 3% to 4% per year; and that there are even estimates that by 2020, 50% of tobacco sales will be for alternative products [5]. Such estimates seem entirely possible although the timescale looks a little optimistic; our estimate would be 25% by that time assuming that the regulatory climate is favorable. We should remember that it took Sweden several decades to achieve their 45% reduction in smoking; though it is true that ecigs are proving far more popular and the uptake is much more rapid.


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Notes

[1] This is often referred to now as the 'tobacco-related mortality rate'. In effect this is a misnomer, because if the smoke is removed, the mortality rate can drop by such a large amount that it reaches near-zero levels. It is more accurate (though admittedly not strictly correct) to use 'smoking-related mortality rate' since for all practical purposes, in Western countries at any rate, where oral tobacco has low to near-zero risk*, smoking kills - not tobacco.
* Lee & Hamlin's meta-analysis of 89 ST trials clearly shows this.

[2] Quotes from the experts

[3] I can say this with some certainty because I am one such person. One side of my family has lung issues, so this is a genetic predisposition. Normally, however, there is no indication of any lung performance outside of normality for me: when younger I could easily run 10 miles or spar ten rounds in the ring (though not on the same day...) - and frequently did so. However my lungs are unusually sensitive to irritants such as dust or mold spores.

One day recently, I received a new brand of e-liquid to try out, and on day 2 noticed some breathing issues. On day 3 breathing was becoming very difficult. On day 4 I was in trouble, and had stopped using the new brand as by then I'd realized what the culprit was. If I had continued, I would have been in hospital without a shadow of a doubt, and would have been in deep trouble. It eventually cleared up completely, after three weeks.

This has never happened before or since, but as you can imagine, I steer well clear of that brand now. On the other hand it does make me a useful e-liquid tolerance-issues tester...

[4] Regulatory capture - Wikipedia, the free encyclopedia

[5] http://www.cspnet.com/news/tobacco/a...st-e-cigs-2012
This drop in sales does not align with the generally accepted decline in smoking prevalence of somewhere around 0.4% (or less) annually, and could be due to a combination of black market tobacco sales and buyers switching to alternatives.

[6] A Death Certificate in this particular case might reliably state the causes of death as:
1. Pneumonia
2. Emphysema
3. Exacerbation of tendency to pneumonia by use of an e-cigarette


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