Saturday, 28 September 2019 17:39

By Dr Farsalinos

(I apologize for the length of the article)

It is ironic to realize that today’s period of information revolution has not only improved access and education for everyone but has also resulted, in many cases, in an unprecedented spread of misinformation and confusion. Take for example the recent case of e-cigarettes and lung disease cases, a story that will be listed in public health history books as one of biggest campaign of misinformation and public deception ever. An immoral “moral panic” campaign based on fiction, intimidation, terror, confusion and misinformation.

The recent, serious outbreak of acute respiratory failure has been presented (with impressive titles) in several articles (such as here and here) as linked to vaping and e-cigarettes while in reality it is linked to THC oils, illicit THC oils. There seems to be an uncontrolled, widespread black market of THC products for which none takes responsibility and none is held accountable. Or maybe, in an effort to avoid any responsibility and accountability (which would be bad news for public relations) some have decided to blame the “eternal enemy”: the e-cigarette.

It is unfortunate that people who have no expertise in this matter and rely on the media and experts to receive valuable information and make informed decisions are passive receivers of the most irrelevant, unreliable and confusing information they can possibly receive.

Take for example the recent article in Bloomberg news. The authors of the article tried to make an in-depth investigation on the recent outbreak of lung disease in the US by looking at past case reports, taking interviews from several scientists and presenting evidence from published studies. Although I am not questioning the motives of the authors, the end-result is a collection of confusing and irrelevant information that, for the most part, is unrelatedt to the disease outbreak in the US and provides no real insight about anything; instead, it misinforms the public.

While it is true that there were sporadic case reports in the past 10 years, there are thousands of case reports in the literature for anything you can imagine. Take for example the case of paracetamol, the most commonly used and most popular painkiller in the world (case reports here, here, here, here, and this is just a tiny sample). Sporadic case reports spanning over a period of 10 years are irrelevant to an outbreak of hundreds of serious lung failure cases which happened within a few weeks, including more than 10 deaths, in just one country. Interestingly, the words “THC” and “marijuana”, which are largely the culprits of this outbreak, are mentioned only once, in an article that has more than 2000 words!

Why is THC oil, not conventional e-cigarette products, the culprit of the outbreak? For many reasons. First, the main clinical manifestation of the disease is lipoid pneumonitis (or eosinophilic pneumonitis, which also can be attributed to inhalation of oils) which probably means that exogenous lipids oils or other hydrocarbons were inhaled. Conventional e-cigarette liquids (i.e. flavored nicotine or non-nicotine liquids) are water soluble. Therefore, oils are not needed and cannot be used as solvents; instead, propylene glycol and glycerol (which are alcohols, polyols; not oils) are used as solvents. In contrast, THC is lipid soluble and difficult to dissolve with common solvents. In an effort to "thicken" illicit THC solutions, it is possible that high levels of oils were used as solvents (not only because THC is soluble to oils but also due to their high viscosity). Vitamin E is a lipid soluble additive that is dissolved in oils in all vitamin supplements (which of course are made to be ingested, not inhaled). Of course, THC as a compound is NOT the cause of the outbreak since it has been inhaled for years without any acute intoxications. Similarly, conventional, nicotine e-liquids are NOT the cause of the outbreak because they have been used for 10 years, and are still being used today, by millions without any acute intoxications. This is another reason why nicotine liquids cannot be the reason for the recent outbreak. THC oil inhalation through a cartridge and using a battery device (what many people call "e-cigarette") is a relatively recent phenomenon, which however has evolved into an uncontrolled black market with unknown manufacturers, no product standards and no quality control. More importantly, THC oil inhalation is not vaping and these are not e-cigarette products. The fact that cartridges with a resistance and batteries are used to evaporate the THC oil does not make this an e-cigarette. The paradox of the recent media reports discussing about vaping and e-cigarettes is similar to suggesting that glass is the cause for binge drinking because everyone drinks alcohol from a glass. It makes no sense. In fact, this is not even the case for THC oils since they are sold in the black market in prefilled cartridges (closed systems), not in refillable bottles.

Going back to the article in Bloomberg news, experts were quoted saying that “We're conducting a big, uncontrolled and poorly documented set of chemistry experiments inside people’s lungs”. This is the frequently-mentioned argument that we do not know what will happen after 20 or 30 years of using e-cigarettes. Interestingly, this is the same “experiment” (in reality it is not an experiment) that we do with every product ever marketed in the history of humanity. I challenge anyone to show me a product that was marketed only after collecting 20 or 30 years of clinical epidemiological evidence. This is simply impossible to happen. I wonder, was it a 40 years experiment for the population when ACE-inhibitors, one of the commonest antihypertensive medications, were recently found to increase the risk for lung cancer by 20-30% when used for more than 5 years? ACE-inhibitors were first marketed in 1980 (captopril). These very common antihypertensive medications are expected to be used for years, even decades, by some patients (for example, my father takes an ACE-inhibitor daily for the past 20 years). The recent study that found a higher risk for lung cancer was published in October 2018. Of course, before marketing ACE-inhibitors, there was no study examining the effects of intake for 10, 20 or 30 years, despite knowing that these medications will be used for such long periods by millions of patients. In an accompanying editorial to the recent study, the author correctly and appropriately mentioned that: “Nonetheless, in an individual patient, concerns about the long term risk of lung cancer should be balanced against gains in life expectancy associated with use of ACEIs.” This is a reasonable and appropriate statement, and common practice for all medications (since all medications and medical procedures have side effects and complications). But we apply double standards for e-cigarettes.

This is not, however, where confusion ends in the Bloomberg article. The potential chronic effects of propylene glycol and glycerol inhalation that are extensively discussed in the article are irrelevant to the acute lung failure cases in the US. The latter have evolved over a period of few days or weeks. Everything mentioned in the article that refers to chronic effects is not related to the recent outbreak. But the reader obviously will be unable to make the distinction. For example, they mention a recent study by Baylor researchers finding fat deposits in the lung of animals which were attributed to propylene glycol and glycerol exposure. This is referring to the study by Madison et al. which again has nothing to do with the recent outbreak; it was a long-term study in mice and the observed effects have no clinical or experimental relevance to the recent outbreak of acute lung injury. Interestingly, everyone seems to be ignoring the important findings of this study that while mice exposed to tobacco cigarette smoke caused developed serious chronic lung inflammation and emphysema, no such effects were observed with e-cigarette exposure. Additionally, this study sparked a debate that the effects of propylene glycol inhalation are unknown and have never been studied. This is not true. In the 1930s and the 1940s, there was extensive research on propylene glycol inhalation because propylene glycol was found to have antibacterial and antiviral properties both in animals and in humans (Robertson OH, Bigg E, Miller BF, Baker Z. Sterilization of air by certain glycols employed as aerosols. Science 1941;93:213; Henle W, Zellat J. Effect of propylene glycol aerosol on air-borne virus of Influenza. Proc Soc Exper Biol & Med 1941;48:544; Robertson OH, Loosli CG, Puck TT, Bigg, E, Miller BF. The protection of mice against Infection with air-borne Influenza virus by means of propylene glycol vapour. Science 1941;94:612; Harris TH, Stokes J Jr. The Effect of propylene glycol vapour on the incidence of respiratory infections in a convalescent home for children: preliminary observations. Am J Med Sci 1942;204:430; Harris TH, Stokes J Jr. Air-borne cross infection in the case of the common cold: a further clinical study of the use of glycol vapours for air sterilization. Am J Med Sci 1943;200:631; Lester W Jr, Dunklin E, Robertson OH. Bactericidal Effects of Propylene and Triethylene Glycol Vapors on Airborne Escherichia coli. Science. 1952 Apr 4;115(2988):379-82). In 1947, Oswald Hope Robertson and coworkers published what is still today the most comprehensive study examining the safety of propylene glycol inhalation in animals. He exposed rats and monkeys to atmosphere supersaturated with propylene glycol for 6 to 18 months and found no adverse effects in the lungs or any other organ. Another paradox is that while everyone focuses on cell and animal studies, which in many cases have limited clinical context, they ignore clinical data. Studies in smokers with asthma and COPD who have been followed-up for 2 and 3 years, respectively, have shown that switching from smoking to e-cigarette use is associated with an objective improvement in respiratory function.

Another irrelevant story presented in the Bloomberg article is about diacetyl and acetyl propionyl (pentanedione). This part of the article begins with an incorrect statement that a researcher at the National Institute for Occupational Safety and Health warned FDA regulators in 2015 about these two ingredients in some e-cigarette liquids. In fact, myself and scientists from USA were the first to publish a study analyzing 159 e-cigarette liquids, mainly from Europe and the US, for the presence of diacetyl and pentanedione. The study was published in 2014. To the best of my knowledge, this still is the only study which compared the levels of the two chemicals between e-cigarette liquids and tobacco cigarette smoke. We found that the average levels found in e-cigarette liquids were 100-fold lower for diacetyl and 10-fold lower for pentanedione compared with tobacco cigarette smoke. The Bloomberg article mentions nothing about the presence of these chemicals in tobacco cigarette smoke.

As many of you may know, Bloomberg news is founded and owned by Michael R. Bloomberg who, as mentioned at the bottom of the article, has campaigned and given money in support of a ban on flavored e-cigarettes and tobacco. In fact, he has launched a crusade against e-cigarettes. It is interesting to know the facts and believes that drive the motivation to campaign against e-cigarettes. Michael R. Bloomberg appeared recently in CBS this morning (internet access from within the US is needed to view the video) to discuss about the issue of e-cigarettes. Among the numerous untruthful statements that were mentioned in that short interview, I present here just four:

In a question about the assessments of Public Health England and the Royal College of Physicians that e-cigarettes are 95% less harmful than smoking, he responded: “I mean, come on, let’s get serious”. During the discussion about youth use of e-cigarettes, he mentioned: “Just think, if your kid is doing this and ends up with an IQ 10 or 15 points lower than he or she would have had…” This is obviously an untruthful statement since no study has ever shown that nicotine causes low IQ levels, while links between nicotine and developmental brain defects are mainly related to smoking or are derived from extreme nicotine exposure in experimental animals. We have seen a similar situation with nicotine causing atherosclerosis in animals, a finding that was rejected when long term epidemiological studies of snus users found minimal effects of cardiovascular health. Moreover, nicotine has been found to improve memory and concentration and has beneficial effects in several neurological conditions such as Alzheimer’s disease and Parkinson’s disease. Of course, the evidence does not suggest that we should recommend nicotine use to the general population. In a discussion about e-cigarette use and smoking cessation, he stated that: “They’ve never released any evidence whatsoever that it does anything to help stop you smoking.” The truth is that numerous population studies and a recent randomized controlled trial have proven the effectiveness of e-cigarettes as smoking cessation aids, while at the same time they are not used as medications. Just after the above mentioned statement, he said: “In fact, most people that vape never smoked before.” In all countries where e-cigarette use in the population has been monitored we find that e-cigarette use is largely confined to current and former smokers while use by never smokers is rare. For the US, I present below a graph with official data from the 2016 and 2017 (pooled) National Health Interview Survey, a population-representative US survey conducted by the National Center for Health Statistics. The graph shows that the vast majority of e-cigarette users are current or former smokers.

Therefore, the founder and owner of Bloomberg news, the person who has spent millions in a campaign against e-cigarettes, has been motivated by misinformation, false information and an ideological, dogmatic approach of ignoring or rejecting evidence that does not fit his own predetermined views (something we usually call “confirmation bias”) and insulting organizations who disagree with his views (something we usually call “if you don’t like the message, kill the messenger).

I’ve never heard any scientist suggesting that e-cigarettes are absolutely healthy and safe, and that anyone can or should use them. E-cigarettes carry a residual risk, minimal compared to smoking, which we will be able to quantify over time. However, there is no doubt that e-cigarettes are by far less harmful than smoking and they fit perfectly to the core definition of harm reduction, a strategy that we practice everyday in our lives (seatbelts, helmets, condoms, medicine). The crusade against e-cigarettes is based on false assumptions that e-cigarettes (instead of illicit THC oils) are the cause of the acute lung disease outbreak, and is being propagated by presenting irrelevant information to the public leading to major confusion, misinformation and misperceptions. Ironically, the campaigns and regulatory initiatives that are supposed to combat the problem of the recent disease outbreak focus on flavors while it is most certainly impossible that any person who decides to use illicit THC oils for inhalation does it because of flavors. At the same time, even suggesting that conventional e-cigarette liquids (i.e. flavored nicotine liquids) that have been available for 10 years globally are responsible for this disease outbreak (only in the US) defies every possible epidemiological principle. The prevailing misinformation and the resulting regulatory reactions have and will certainly result in a wave of relapse back to smoking for many of the millions of vapers who have managed to quit smoking with e-cigarettes. This is a much bigger public health tragedy compared to the recent disease outbreak, considering that more than 1200 Americans die daily from smoking-related disease. I have no doubt that history will record the situation today as one of the most untruthful and damaging campaigns for public health.

My suggestions to readers are the following:

To smokers: try to quit by yourself; if you fail, try to quit with medications and professional help; if you fail or you are unwilling to use medications, you have to try tobacco harm reduction products (e-cigarettes, Scandinavian snus, heated tobacco cigarettes). The goal should always be to quit smoking; reducing smoking consumption is not enough.

To never smokers (adults and youth): e-cigarettes are not absolutely safe and harmless; thus, there is no need to be exposed to any unecessary risk (even if the risk may be small).

Everyone should make informed decisions based on the TRUTH. But where is the truth?