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expert reaction to study looking at e-cigarette vapour and vascular effects in mice and smokers

Research, published in the European Heart Journal, reports on the relationship between e-cigarette use and damage to the brain, blood vessels, and lungs. 

 

Prof Peter Hajek, Director of the Tobacco Dependence Research Unit, Queen Mary University of London, said:

“The authors detected two effects.  In human smokers, nicotine from e-cigarettes produced a typical acute stimulant effect, also seen after drinking coffee, that on its own signals no danger.  In mice and in tissue samples, acrolein, a chemical that can be generated when e-liquid is fried, had more damaging effects.  This however is not relevant for human vapers.  Frying e-liquid produces this chemical, but this also produces aversive taste that vapers avoid.  Human vapers have acrolein levels that are similar to non-smokers and much lower than in smokers.”

 

Prof Ajay Shah, Head of School of Cardiovascular Medicine & Sciences, and BHF Professor of Cardiology, King’s College London, said:

“This study convincingly shows that the use of e-cigarettes in people who are cigarette smokers causes a short-term additional impairment of the function of the inner lining of blood vessels – the endothelium.  It is recognised that persistent abnormal function of the endothelium predisposes in the long-term (several years) to furring up of the arteries which can lead to heart attacks or stroke.  The effect here of an e-cigarette vaping episode on the endothelium is similar to the short-term effects of cigarette smoking, high cholesterol or diabetes, but whether it would have similar long-term detrimental effects on health cannot be determined from this study.  It is important to note that the researchers did not study the effects of e-cigarettes on healthy non-smokers but only in people who regularly smoke cigarettes and whose endothelium may already be slightly abnormal – so we cannot fully extrapolate these results to non-smokers.  They also only studied the effects of one episode of vaping.

“The second part of the study was to expose mice to e-cigarette vapour for up to five days and assess the impact on vessels, the lungs and the brain.  The researchers found evidence of some damage to all these organs but these results are less straightforward to extrapolate to humans, and the researchers did not include all the appropriate control groups to improve confidence in this result.  The conclusions from the animal studies regarding possible effects on the lungs and brain therefore require further research in people to assess if the same happens in humans.  However, it is quite clear that e-cigarettes appear to cause potentially harmful effects on the endothelium in people who are regular cigarette vapers, indicating that they are not harmless.”

 

Dr Gavin Sandercock, Reader in Clinical Physiology (Cardiology) and Director of Research, University of Essex, said:

“This study was done in mice and in 20 human smokers.  The mouse work is very complex but I didn’t find it very compelling.  The human work is complicated by the fact the people were current smokers so we can’t tell how much of the observed effect could be down to smoking-related damage.  All the effects vaping had on the human smokers were short-term changes we know happen when nicotine enters the body; by smoking cigarettes, vaping, using patches or gum’ – they are not specific to vaping.  Many of the potential health problem suggested in the study are not based on the humans who took part, but come from experiments done in mice.  This makes the findings difficult to generalize to human health.

“The authors say that “in the UK, 1.6% of those aged 11-18 use e-cigarettes more than once a week, compared with 0.5% in 2015” – but these numbers are meaningless without knowing how many of the 1.6% were already smokers, or how many would have smoked cigarettes anyway even if they didn’t vape.  Vaping may be less healthy than breathing air but all the evidence so far suggests it is nowhere near as unhealthy as smoking cigarettes.  Because cigarettes are so harmful, much more harmful than vaping, any child who vapes instead of smoking is better off.  Likewise any smoker who switches to e-cigarettes is likely to improve their health compared with someone who continues to smoke cigarettes.

“The authors describe how they measure blood flow and arterial stiffness in 20 current smokers before and after vaping an e-cigarette.  But we know cigarette smoking causes endothelial dysfunction – that is a fact.  The changes described here following vaping are short-term, small, not necessarily indicative of poor health by themselves, and might have been very different in non-smokers or even in habitual vapers compared with this small sample of smokers.  So we can’t tell how much of these effects were down to the fact these people were smokers.

“The authors say “Our data may indicate that e-cigarettes are not a healthy alternative to traditional cigarettes, and their perceived ‘safety’ is not warranted” – but this argument fails to address the ‘relative’ safety of vaping over smoking cigarettes.  Cigarettes increase the risk of early death by at about one third, and there is as yet no actual evidence that e-cigarettes are a threat to health.  There is certainly no evidence that they are worse than or as bad as cigarettes.

“The authors say “The e-cigarette epidemic in the US and Europe, in particular among our youth, is causing a huge generation of nicotine-addicted people” – I do not agree with this statement.  According to the CDC last year, smoking rates fell to a record low of 14% in the US, and the graphs from the WHO1 show how much smoking has declined in the Germany (where this study took place) and across Europe.  The WHO also project further declines in smoking prevalence – which does not support any suggestion that there is a rise in nicotine addiction.

“People would only be endangered when switching from cigarettes to e-cigarettes if the e-cigarettes were known to be MORE of a danger to health, and there is no evidence to suggest this is true.”

1 http://www.euro.who.int/__data/assets/pdf_file/0009/402777/Tobacco-Trends-Report-ENG-WEB.pdf?ua=1

 

Prof Tim Chico, Professor of Cardiovascular Medicine and Honorary Consultant Cardiologist, University of Sheffield, said:

“This study was conducted in both humans and mice and shows clearly that e-cigarettes have negative effects on the cardiovascular system.  These negative effects (increased stress in the blood vessels and worse blood vessel function) do not completely prove that e-cigarettes will definitely lead to forms of heart disease such as stroke and heart attack, as this would need a very large study over many years.  However, these results do certainly sound a note of caution that it is quite possible that using e-cigarettes increases risk of heart attach and stroke later in life.

“Although I still suspect that it is unlikely that e-cigarettes are as harmful as conventional tobacco, any rising rates of e-cigarette use in people who have never smoked conventional tobacco products would be of particular concern.  It is not true that e-cigarettes are harmless; this study found that e-cigarettes produce many toxic products which can be damaging to healthy tissue.

“The authors of this study call for countries to consider banning them.  This raises a challenging question, since a ban at this stage would be in the absence of clear evidence of long term increases in risk of heart disease.  However, such evidence will take years to accumulate while people are possibly exposing themselves to harm.

“This study should not prevent anyone from taking steps to cut down or quit smoking tobacco, but if e-cigarettes are used then they should be used for the minimum of time and as a bridge to stopping smoking (including stopping vaping) completely.  I do welcome this study as an important pointer towards the potentially harmful nature of e-cigarettes.”

 

Prof Jacob George, Professor of Cardiovascular Medicine and Therapeutics, University of Dundee, said:

“This is a basic science in-vitro and mouse study with a 20 human subject sub-study bolted on, where a single e-cigarette was vaped by volunteers and vascular function tested before and after.  We still need much more research before we could translate this pre-clinical data to a coherent clinical picture.

“With regards to the human study, it is impossible to draw any firm conclusions from these small, single exposure studies which is why larger randomised clinical trials are needed.  The results are also at odds with larger and longer duration clinical trials by D’Ruiz et al1 and Farsalinos et al2 that demonstrate reduction in blood pressure with e-cigarette use, which implies improvements in vascular function with e-cigarette use.

“Because this study couldn’t tease out the effects of prior tobacco cigarette use and dual-use (most vapers are ex-smokers) on these volunteers, the conclusions are far from clear.”

1 Regul Toxicol Pharmacol 2017; 87:36–53

2 Intern Emerg Med 2016; 11:85–94

 

Prof John Britton, Director of the UK Centre for Tobacco & Alcohol Studies and Consultant in Respiratory Medicine, University of Nottingham, said:

“This study suggests that vaping constricts blood vessels in humans and has a range of effects on vessels in mice.  I’m not a cardiologist so I don’t know how convincing those changes are, but I do know that this study cannot tell us which of these effects are due to the nicotine in the vapour, and which (if any) are due to other vapour components.  We know nicotine constricts blood vessels, and is obviously essential if e-cigs are to be effective as a replacement for smoking.  So we need to know whether any of these changes happen with no nicotine in the vapour, which we can’t tell from this study.

“Electronic cigarettes are not safe, they are simply likely to be far less damaging than tobacco cigarettes.  This paper adds evidence on e-cigarette safety but does not address their harm relative to smoking.  It’s that relative harm that matters – and that‘s why every smoker who switches from smoking to vaping will be much better off, and this study does not change that fact.”

 

Prof Paul Aveyard, Professor of Behavioural Medicine, University of Oxford, said:

“This paper reports a small study in 20 human volunteers, in mice, and in cell cultures, showing that vaping adversely affects the function of the lining of arteries.  Poor function of the lining of the arteries is one of several mechanisms through which smoking causes heart attacks and strokes, so this finding is important but needs to be kept in perspective in terms of how harmful we know smoking is.  Unfortunately, that perspective is lost here.

“There is no evidence in the UK that there is a large market for e-cigarettes among young people who do not smoke.  While many young people try e-cigarettes, they do so only a few times, and regular use in young people who do not smoke is rare and, among those who do vape, vaping is infrequent.  Meanwhile, several million people in the UK try to stop smoking every year by using an e-cigarette and we know that e-cigarettes will help them succeed in stopping.  Nearly all adults who use e-cigarettes regularly do so either as part of an attempt to stop smoking or to prevent themselves returning to smoking.

“Should current and former smokers who vape stop vaping as a result of this research?  The research would have been helpful to people facing this choice if it had compared the effects of vaping with smoking, but it did not do so.  It showed only that vaping impaired the function of arteries, but it is not possible to know how harmful this effect is long-term.  For example, the effect described in this paper on the lining of arteries from vaping can be seen in similar studies of the effects of smoking.  The studies of smoking showed that the poor function of the arteries was reversed by taking vitamin C, but we are certain that taking vitamin C does not prevent heart attacks or strokes, even in people at high risk, so this cannot be the only route by which smoking harms our arteries.  UK public health agencies, charities, and doctors’ organisations advise people who cannot stop smoking to switch to vaping.  These results should not deter people from doing so.”

 

‘Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2)’ by Marin Kuntic et al. was published in European Heart Journal at 00:05 UK time on Wednesday 13 November 2019.

DOI: 10.1093/eurheartj/ehz772

 

Declared interests

Prof Ajay Shah: “None.”

Dr Gavin Sandercock: “I have no conflict of interest to declare.”

Prof Tim Chico: “No conflicts.”

Prof Jacob George: “None.”

Prof John Britton: “No conflicts to declare.”

Prof Paul Aveyard: “I have no conflicts.”

None others received.

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