The biomarkers lie

posted by Carl V Phillips

Our colleagues in the UK have predicted that there will be a flurry of new studies on e-cigarettes in the run up to the UK government considering how to regulate them, and perhaps this press release from the Greek research team of Christina Gratziou at the European Respiratory Society (ERS) meetings, which we started discussing yesterday, is an example.  Apparently those authors were just trying to get out a quick attack on e-cigarettes.  Others might want to just get in on this new area of research to bolster their career.  Still others might (gasp!) be genuinely interested in finding out the truth about e-cigarettes (a category that we hope includes most everyone who is pro-THR — the cause, and especially the product users, do not benefit from people doing junk science that is biased to overstate the benefits of THR).

Whichever category someone falls into, they basically have three options for research methods.  They can look at the chemistry of the vapor and compare that to existing knowledge about the effects of the chemicals in the relevant quantities (which has been done honestly by quite a few people — the dishonest ones that have already been covered in this blog are not the norm).  They can pointlessly torture innocent animals do toxicology, as was discussed here a few days ago, though it is unlikely that much of that will happen (no one is likely to learn much new about the effects of the simple chemicals in e-cigarettes).  Or they can look at “biomarkers”.  We would really like to have epidemiology, but that is not an option.

(Aside:  It is often said that the reason we cannot have the epidemiology is that it would take a long time to get.  That is certainly true, but it is much worse than that:  The current products will not ever be used by anyone long enough to get epidemiology on them.  The tech is changing too fast, so there will never be people who use the same novel THR products, exclusively enough and for long enough, to ever have the epidemiology.  Indeed, there is a similar problem for many types of short-term research too, like measuring the exact level of a particular contaminant in a particular e-cigarette.  Who cares?  It will not be the same in the products that most people are using next year.  I tried to explain this to the people who were excited about doing e-cigarette research at last year’s SRNT meeting, but it seemed to just baffle them.  I might as well have been speaking Greek(!) to them — they are so used to studying a non-varying product (cigarettes) that they have no idea that most scientists have to deal with a changing world.  And it is playing out just as I expected, with people doing hyper-detailed studies of something that will not exist in a year.)

A biomarker is any measurable effect of an exposure on people’s bodies.  Typically the term excludes anything that would be called a disease in itself, though this is not an important distinction.  A biomarker is anything like heart rate, immune cell count, lung capacity —  anything that can be measured about a body’s state or functioning.  The advantage of looking at biomarkers is that we can look for changes that occur long before a disease event might occur.  For example, we could compare a collection of these biological measures from people who have been vaping for a year to similar people who quit smoking a year ago without any substitute product, and see if there are differences; we would not know for sure what any differences we observed might mean for eventual outcomes that really matter (disease), but we could see the differences.

Do not read too much into the title I chose for this post.  Biomarker results are obviously not inherently lies.  Unlike toxicology, they give us an actual measure of the effect a real exposure has on a real person.  But like toxicology, we do not know exactly what the results mean in terms of disease risk, and it is a lie to claim otherwise.  Indeed, almost any press release about a short-term biomarker study will contain lies, because a press release is going to have to make overblown claims about the implications of the study to attract any attention.  Biomarker studies (done well and reported honestly) add to our total body of information, and so can add up to a lot of knowledge, but each result has extremely limited implications that, if reported honestly, would never be of interest to a newspaper.

Also, in a perfect world, we would be doing a lot more epidemiology of the biomarkers of tobacco/nicotine product use — that is, we would be doing long-term epidemiology (study of real disease outcomes) on people whose biomarkers have been measured to see which of those are really associated with eventual disease.  That would potentially be very useful (which is why I have been pushing the players who could actually make it happen to initiate it) but the payoff is far in the future.

So, to turn this background back to the case at hand:  Gratziou et al. measured a very short-term biomarker.  They had someone puff on an e-cigarette a few times and measured airway resistance.  Even ignoring the details of what they did, reported, and claimed, this tells us very little.  In particular, it does not support the lie that they led their press release with (emphasis added):

New research has shown that despite electronic cigarettes being marketed as a potentially safer alternative to normal cigarettes, they are still causing harm to the lungs.

No such claim can be made about these results.  Whatever the possible value of an acute (very-short-term) biomarker, it is difficult to extrapolate that to actual disease (or even “harm”, which can only be interpreted as a change that increases the risk of eventual disease).  It could be that a lifetime of vaping does increase the risk of lung disease, but there is nothing this study could have found — short of catastrophic problems that we already know do not occur — that would have shown that.  Similarly, if the study had found no measurable change, it would have contributed almost nothing to our confidence that vaping does not hurt the lungs in the long run.

A better biomarker study like the one I suggested a few paragraphs back would tell us more, but measuring immediate impacts tells us very little unless they are truly disastrous (which these were not).  We need to encourage the researchers who are really trying to learn something useful to do the more useful biomarker studies on experienced vapers compared to non-users, rather than just the quickie lab encounters which are cheap and easy (and which tell us something we can add to our body of knowledge, but not much).  These will still only be biomarker studies, not full-on epidemiology, but they can be done now and they will tell us a bit more that is epidemiology-like.

Of course, this was all a long way of getting to the point that other commentators (see my link from yesterday’s post for a good one) led with:  The study did not demonstrate any harm to the lungs.  But I think there is some added value in showing the intermediate steps, as it were, when pointing out why something was a lie.

The research was incapable of producing any terribly useful information, but it could have been a slightly useful contribution to our overall understanding if it had been honestly analyzed and reported.  But it was not, and so it contributed only to misunderstanding.  More on why the reporting itself (even apart from the simple lies) was dishonest as this series continues.

…to be continued…