Recent reports of a death in the US linked to vaping, and of almost 200 cases of lung disease, have caused alarm about the widespread use of e-cigarettes.
Director of the US Centers for Disease Control and Prevention (CDC), Dr Robert Redfield, warned that: "E-cigarettes are not safe for youth, young adults, pregnant women, or adults who do not currently use tobacco products."
Yet in the UK, Public Health England (PHE) continues to advocate their use as part of smoking cessation services. Earlier this year, a study showed that e-cigarettes may be more effective than standard nicotine replacement therapy (NRT) in helping people to stop smoking.
We look at how attitudes to e-cigarettes and related products differ internationally, how they are regulated in the UK, Europe, and the US – and what might happen to regulation after the UK leaves the EU.
E-cigarettes: 95% Safer Than Smoking?
E-cigarettes vaporise a liquid that is breathed into the lungs. Most e-cigarette liquids contain nicotine, propylene glycol and vegetable glycerine, and flavourings. Nicotine, while highly addictive, is not thought to cause cancer. However, it raises blood pressure and heart rate, and stimulates the nervous system.
In 2015, Public Health England published a report declaring that "e-cigarette use is around 95% less harmful to health than smoking". The report was based on an evidence review by Professor Ann McNeill, professor of tobacco addiction at Kings College London and psychologist Professor Peter Hajek, director of the tobacco dependence research unit at Barts and the London School of Medicine, who explained their 95% figure by stating that the main carcinogens in tobacco smoke are either absent from e-cigarette vapour, or present in quantities below 1%. They added that, while flavourings "may pose a risk" in the long term, "we consider the 5% residual risk to be a cautious estimate allowing for this uncertainty".
No-one is saying that e-cigarettes are completely safe. Smoking tobacco is one of the worst things a person can do for their health, so finding that e-cigarettes are safer than smoking tobacco sets the bar low. Half of all long-term smokers die early from smoking-related diseases.
Death Linked to Vaping
The Illinois Department of Public Health reported in August the death of "an individual who had recently vaped and was hospitalised with severe respiratory illness". It caused great concern in the US, where the CDC and the Food and Drug Administration (FDA) held a joint press briefing on August 23rd. The CDC said it had received reports of 193 potential cases of lung disease linked to vaping, from 22 states. By September 6, that had risen to more than 450 reports of potential cases, with five deaths. An estimated 10.8 million people in the US used e-cigarettes in 2018.
A rapid review of 53 cases, published in the New England Journal of Medicine on September 6th, revealed that 80% of people taken ill who were interviewed about their e-cigarette use said they had used cannabis-based THC-containing products as well as nicotine.
In an accompanying editorial, Professor David Christiani, director of the Harvard Education and Research Center for Occupational Safety and Health said: “Until the investigation into the cause of this epidemic of vaping-induced respiratory injury is complete, no conclusions can be drawn as to which compound or compounds are the causes of injury.”
However, Prof Peter Hajek, director of the Tobacco Dependence Research Unit, Queen Mary University of London (QMUL), said in a statement via the Science Media Centre: "The mystery seems to have been resolved now, with cases being traced to a contaminated marijuana extract. Although the scare is being used to put smokers off switching from cigarettes to much less risky vaping, it has nothing to do with e-cigarettes as they are normally used in this country."
When cases were first reported, the director of the CDC warned of "serious risks" associated with vaping, stating that: "CDC has been warning about the identified and potential dangers of e-cigarettes and vaping since these devices first appeared."
UK experts were more sanguine even before the findings about THC. Professor Linda Bauld, professor of health policy at the University of Edinburgh, told the Science Media Centre that no reports in the UK of similar problems had been received, and that "we have no evidence that they [the reports of illness] are linked to the types of e-cigarettes used by over 3 million people in the UK".
She added: "Details from the USA are sketchy and clearly further investigation is needed, but these cases appear to be linked to contaminated or black market e-liquids. They may also be linked to vaping substances other than nicotine including cannabis oils that have been tampered with or modified."
A spokesperson from the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) told Medscape UK there had been 12 reports of "adverse reactions associated with nicotine-containing e-cigarettes" between 22nd August 2018 and 21st August 2019, of which seven involved respiratory-related reactions. None of the patients needed admission to hospital.
"Based on the evidence reported in these cases, the MHRA do not consider these reports to indicate severe or dangerous lung injury similar to those reported in the USA," she said. "It is essential to note that a report of an adverse reaction does not necessarily mean that it was caused by the e-cigarette, but a suspicion by the reporter that the e-cigarette may have been the cause."
Dr Nick Hopkinson, reader in respiratory medicine at Imperial College and a board member of Action on Smoking and Health, told Medscape UK the US reports were "something really important that needs to be followed up to see what's causing these".
He added: "We just haven't seen that in the UK… I was expecting it to be more of a problem; when people are inhaling organic compounds of one sort or another you expect a proportion of people would have allergic reactions. Assuming these are accurate cases it may be something very specific about individual chemicals or drugs."
Stricter Regulation
Since 2016, e-cigarettes in the UK have been subject to regulation via the EU's Tobacco Products Directive 2014/14/EU, known as the TPD.
This directive restricts the strength of nicotine and the size of e-cigarette tanks and refills; bans certain ingredients, and provides minimum standards for the safety and quality of products, including child-proof packaging. It also regulates labelling and information for consumers. Notably, banned ingredients in the UK include diacetyl, a butterscotch flavouring that has been linked to lung disease and is legal in the US.
The TPD would not apply to medicinal products. It was envisaged that e-cigarette manufacturers would seek licenses to market e-cigarettes as smoking cessation aids, which would enable them to produce ranges with higher strength nicotine. However, no e-cigarette products have been marketed for medicinal use in the UK, despite aspirations from PHE to "ensure that the route to medicinal regulation for e-cigarette products is fit for purpose so that a range of safe and effective products can potentially be made available for NHS prescription".
Opinions differ internationally on the place of e-cigarettes in smoking cessation. While PHE envisages a range of NHS-prescribed products, the American Academy of Family Physicians advises members, "current evidence is insufficient to recommend ENDS [electronic nicotine delivery systems, another name for e-cigarettes] for tobacco cessation in adults".
Smoking Cessation Evidence
That evidence strengthened in February 2019, with the publication of a randomised controlled trial of e-cigarettes compared with nicotine-replacement therapy (NRT) as part of a smoking cessation service. The UK-based study recruited 886 adult smokers who had approached NHS Stop Smoking Services. After a year, 18% of e-cigarette users had stopped smoking tobacco, compared with 9.9% of NRT users.
For some doctors, this trial confirmed their efficacy. Dr Hopkinson says: "We've got a very established principle that NRT is a good way to help people quit smoking. E-cigarettes are essentially another form of nicotine replacement so it would be very surprising if they didn't help people quit smoking… I don't think anyone can seriously argue now this trial has been done that e-cigarettes don't help people quit smoking."
However, Simon Chapman, professor in public health at the University of Sydney and a long-term critic of e-cigarettes, said it was "important to recognise that [the study] only relates to those who are using e-cigarettes when linked to face-to-face support from a smoking cessation service. It tells us nothing about their use in the wider population of smokers, which is where many of the concerns lie".
Dr John Cullen, president of the American Academy of Family Practitioners, added: "Scientific studies have not shown that e-cigarettes help people quit smoking combustible cigarettes. In fact, the opposite is often true."
He said last week: "The National Academies of Sciences, Engineering, and Medicine concluded that there is insufficient evidence about the effectiveness of e-cigarettes as cessation aids to quit smoking combustible cigarettes when compared with no treatment or proven cessation treatments."
Critics pointed to the fact that 80% of people using e-cigarettes in the trial continued to use them 12 months on. Dr Hopkinson concedes there is "concern that most people who had chosen to vape were still vaping a year later. We know vaping is much safer than smoking so they are definitely better off – but a proportion would have been using nothing."
He said e-cigarettes would not be his first choice of smoking cessation aid, within a smoking cessation programme. He suggested starting a patient on duel NRT with counselling, only moving on to e-cigarettes or the medication bupropion if that did not work. However, he said he would respect patient choice if a patient wished to try e-cigarettes first.
Dr Deborah Robson, senior postdoctoral researcher in tobacco addiction at the National Addiction Centre, Kings College London, and co-author of PHE's most recent evidence report, told us: "Stop smoking services can't prescribe [e-cigarettes] as they are not licenced as a medicinal product," although some services do recommend them.
She adds: "An effective e-cigarette available on prescription would be welcome... It's also important to ensure that smokers who want to switch to vaping have a wide choice of e-cigarette products available to them and multiple ways of easily accessing them."
What About Kids?
One of the main fears of those concerned about e-cigarettes is the possibility that children and young people may start to use them, even if they have never smoked tobacco. Not only would that expose them to as yet unknown risks, it might also act as a 'gateway' into smoking tobacco.
That fear has been heightened by recent figures from the US, which showed a sharp rise in the numbers of under-18s vaping in recent years. A study found that in 2018, 4.9% of Middle School students (aged around 11 to 14) and 20.8% of High School students (aged 14 to 18) reported vaping in the past 30 days. This represented a 48% rise for middle school and 78% rise for high school students compared with 2011. The researchers said the rise in popularity: "is likely because of the recent popularity of e-cigarettes shaped like a USB flash drive, such as JUUL; these products can be used discreetly, have a high nicotine content, and come in flavours that appeal to youths".
"Fun flavours, attractive packaging, targeted marketing, and ease of use and concealment are among the reasons that youth start using e-cigarettes. Many young people believe they are harmless," Dr Cullen told Medscape UK, adding that many American teenagers think vaping is "even cooler" than smoking.
In March this year, the FDA announced a proposal to restrict fruity flavourings in e-cigarettes, blaming them for "epidemic" levels of use among teenagers.
"We support recently introduced legislation in both branches of Congress that would raise the minimum legal age of sale for tobacco and ENDS from 18 to 21," says Dr Cullen. "We also support efforts that would require graphic warnings on packaging, clean indoor air policies, tobacco-free pharmacies and health care facilities, increased access to tobacco and ENDS cessation services and medication, and restriction of access and marketing of e-cigarettes to children and youth."
Another recent study looked at vaping and tobacco smoking among young people aged 16 to 19 in England, Canada, and the US. It found 8.9% of young people in England, 14.6% in Canada, and 16.2% in the US reported vaping in the past 30 days. Rates increased by 3%, 95%, and 55% respectively, from 2017 to 2018.
In England and the US, figures for smoking tobacco in the past 30 days remained stable, at 16.4% and 12.2% respectively in 2018. But in Canada, rates of tobacco smoking rose from 10.7% in 2017 to 15.5% in 2018. Professor Chapman commented to us: "The Canadian data were particularly alarming. There has not been an increase recorded in teenage smoking in Canada in 30 years." He said the data showed "alarming evidence that upswings in vaping by teenagers can see significant parallel rises in smoking".
However, Dr Hopkinson says UK experience refutes that. "A tiny proportion of children are vaping and those that are often try it just once to see what it's like. There's no evidence children are taking it up because they think it's cool and almost all children who are vaping are also smoking or have smoked. So there's no evidence of any gateway effect," he says.
Figures released by NHS England in August showed that in 2018, 16% of 11-15 year old pupils had ever smoked, down from 19% of pupils in 2016. This was the lowest level ever recorded by the biannual survey. "The evidence just out shows that smoking rates are falling still. So certainly in children we don't seem to have this big problem they have in the US," says Dr Hopkinson.
He put the difference down to the different regulatory regime in the UK. "In the US, they've got themselves into trouble with child use. They do seem to have a lot of never smokers who are vaping and that's clearly a bad thing. They [the US authorities] are desperately trying to catch up having not controlled e-cigarettes effectively in the first place."
Dr Robson agrees that regulation may be behind the difference in experience and attitudes between the UK and US. "In the UK, almost all forms of e-cigarette marketing have been banned since 2016, whereas this is not the case in the US. The EU imposes limits on the amount of nicotine in e-cigarettes; such controls are not in place in the US. The lack of regulatory standards and few marketing restrictions in the US compared with the stricter regulations in the UK (and EU) may account for some of the difference in attitudes."
Regulation and the Brexit Effect
Regulation around the world varies from complete bans on sale and use of e-cigarettes in some countries, to bans on sale of nicotine-containing products in others, to previously light-touch regulation in the US.
In the UK, regulation comes via the EU TPD. At present, it is expected that all EU regulations will be carried over to UK law when the UK leaves the EU. Last year a House of Commons Science and Technology Committee report recommended that this regulation should be reviewed, with a possible change to nicotine levels and size of refills, as well as potential changes to marketing regulations.
In response, the Department for Health and Social Care said: "the Government will review where the UK's exit from the EU offers us opportunities to re-appraise current regulation to ensure this continues to protect the nation's health. The Government will explore those areas identified by the Committee, such as the 20mg/ml maximum nicotine refill limit, a size restriction of 2ml on the tank, a block on advertising e-cigarettes' relative harm-reduction potential and the notification scheme for e-cigarette ingredients."
However, Dr Hopkinson says the TPD is "pretty sensible". "The UK has been a leader in tobacco control in Europe. There's no particular reason why that might change. You need to know the devices are safe and not going to catch fire and so on. I don't think there are any particular changes around that are expected."
Dr Robson agrees: "TPD regulations do not appear to have impeded the 3 million people in England who have taken up vaping or the hundreds of thousands of smokers who have successfully quit with them," she says.
Conclusion
The trouble with the debate around e-cigarettes, according to Dr Hopkinson, is that it tends to "crowd out other topics of conversation" around smoking. The "absolute scandal" he says, is that smoking cessation services are being cut, despite strong evidence that they work to reduce smoking, and that helping someone to stop smoking is one of the most speedily cost-effective things you can do to improve health and save health service money.
Asked if he would like to see more use of e-cigarettes in smoking cessation, he responds: "Honestly, I'd like to see more smoking cessation provision full stop. I don't really care what sort of nicotine replacement therapy people are offered as long as they are getting something."
And yet he acknowledges the safety and effectiveness of e-cigarette use is "a serious question", especially if young people are vaping who would not otherwise have smoked. "Even if they're only 5% the risk of cigarettes, you multiply that over 20 to 30 years of use and that is going to cause health harms if it carries on."
It's sensible to be suspicious of the tobacco industry, which has bought up many e-cigarette and e-cigarette liquid manufacturers. "The tobacco industry wants to maximise profits and it would be perfectly happy if everyone switched from smoking to vaping, so long as they were buying the products from the tobacco industry," says Dr Hopkinson.
However, the tobacco control environment in the UK – from bans on smoking indoors and in workplaces, to regulation around packaging and warnings – coupled with a low adult smoking rate sets the scene to encourage e-cigarette use as a quitting aid.
"Our approach to e-cigarettes has largely been, is there a way we can get [smokers] to quit rather than waiting for them to die?" Dr Hopkinson says. Without a background of strict tobacco control, the risks of a return to higher tobacco smoking or increased dual use of tobacco and e-cigarettes would be much higher, he adds.
Until now, the European regulatory framework has set the scene for a tobacco control environment that means e-cigarettes in the UK are almost entirely used by former smokers and smokers attempting to quit. The danger of regulatory changes post-Brexit would be the rolling back of tobacco control measures, combined with less strict e-cigarette regulations on sale and marketing. If we are to achieve Public Health England's vision of a Smokefree Generation, e-cigarette and tobacco marketing must continue to be treated with caution.
