Electronic cigarettes: harm reduction or another addiction?; the dental perspective

What is an e-cigarette?

The first record of e-cigarettes was in 1965 when a US patent was filed by Herbert Gilbert (US Patent Office # 3200819).4 The recent explosion in e-cigarette popularity is often linked to Hon Lik, a Chinese pharmacist and heavy smoker. He filed a US patent in 2005 for an ‘electronic atomization’ cigarette that contains nicotine without tar’,5 apparently invented after his father, a heavy smoker, died of lung cancer. Hon then developed his business ‘Ruyan’ meaning ‘like smoke’ which recently (2012) sold for $75 million to the Imperial Tobacco Group Plc (Ruyan is now called Dragonite International Ltd).6 Commentators7 have likened the tobacco industry's growing interest in e-cigarettes as an attempt to avoid the ‘Kodak moment’ when the world's leading maker of camera film realized that the world had gone digital and it was too late to catch up.

An e-cigarette essentially comprises a cartridge containing nicotine, diluents and flavourings and an atomizer which heats the liquid to 200 °C8 to produce the vapour.9^,10 E-cigarettes are often described as first or second generation.11 First generation e-cigarettes typically resemble traditional tobacco cigarettes. Second generation cigarettes take other forms but usually contain a tank that the user can re-fill with e-liquid. Figure 1 details the typical construction of a second generation e-cigarette and Figure 2 shows an e-cigarette starter kit. Inhalation of the vapour is termed ‘vaping’ (Figure 3).

The delivery of nicotine is the primary role of e-cigarettes. The nicotine is delivered in an aerosol form, attempting to replicate conventional smoking. It is available in varying doses, including nicotine free versions, suggesting they could potentially have a role as a nicotine replacement as part of a cessation programme. There have been concerns over the accuracy of the stated nicotine concentrations and the ability to deliver consistent vapour concentrations.12 Indeed, the US Food and Drug Administration (FDA) have stated that there is too much variability in the amount of nicotine delivered per puff of any e-cigarette cartridge for them to be considered safe.13 The UK Medicines and Healthcare products Regulatory Agency (MHRA) has stated similar concerns ‘about the quality and inaccurate labelling of electronic cigarettes’.14 Indeed, a 0 mg nicotine capsule yielded 24% of the nicotine generated from a 1 mg conventional cigarette, raising concerns over misleading labelling.15 Although disputed, it is often quoted that the lethal dose of nicotine is around 10 mg in children (30–60 mg in adults) and concerns have been raised16 regarding the potential lethal consequences of inadvertent consumption of an e-cigarette vial as they can contain up to ten times this amount (100 mg).17

A major advantage of e-cigarettes over conventional smoking is the significant reduction in carcinogenic compounds. Cigarette smoke from burned tobacco contains many carcinogenic compounds, the most important groups being tobacco-specific N-nitrosamines and benzo(a)pyrine.18 Studies of e-cigarette vapour have detected tobacco specific N-nitrosamines, but only at trace levels (0.008 ug), compared to burnt tobacco cigarettes (6.3 ug).19

On the other hand, there has been much concern about potential contaminants in e-cigarette vapour and the FDA issued a public warning20 in 2009 after completing an analysis. Diethylene glycol, a known carcinogen (and used in anti-freeze) has been detected in a small number of e-cigarettes tested by both the FDA and MHRA.9^,15 The source of the diethylene glycol is unclear but it has been suggested that it could be from using non-pharmological grade propylene glycol. Lead, nickel and chromium have been detected in e-cigarette vapour, in some cases higher than in burnt tobacco.19 The authors postulate that these are derived from the filaments inside the e-cigarette atomizer and that better manufacturing and design would significantly reduce these trace metals.

Several other studies21^,22^,23 have found low or undetectable levels of these compounds in e-cigarette vapour. Goniewicz et al24 studied 12 brands of e-cigarettes and found levels of toxicants to be 9–450 times lower than in burnt tobacco, highlighting the potential for using e-cigarettes as a harm reduction tool in smokers unwilling to quit.

Propylene glycol makes up 90% of the solution and is a commonly used solvent in food and medicine manufacturing. Glycerine helps produce greater vapour to look and feel more like the conventional smoking experience, and can add some sweetness. Flavourings are often added, as nicotine is neutral, and there is a huge range of flavours available ranging from ‘Tobacco’ to ‘Tiramisu’ and ‘Pomegranate’ to ‘Pina Colada’.

Additional compounds can be added to the e-cigarette mixture with claimed additional benefits. For example, rimonabant (zimulti) is marketed to aid weight loss and reduce smoking addiction, while tadalafil is marketed to increase sexual activity. It has been suggested that only small amounts of these substances are transferred to the vapour.25

Health effects

E-cigarette manufacturers promote vaping as a safer alternative to conventional smoking. Indeed, to date there is no evidence to suggest that e-cigarettes are more harmful than conventional cigarettes. However, there is little research into the immediate and long-term health effects of e-cigarette use.14

Studies have shown detrimental acute effects on pulmonary function.26^,27 Potential cardiovascular effects were discussed by Lippi et al, including the increased risk of cardiac arrhythmias and hypertension, which may predispose some users to increased risk of cardiovascular events.28 Exogenous lipoid pneumonia, a rare form of pneumonia, has been linked to e-cigarette usage in a case report.29 Exposure to the glycerine-based oils in e-cigarette vapour was proposed to be the source, with radiological signs and clinical symptoms improving with abstinence from the e-cigarettes.

One of the key potential health benefits of e-cigarettes is the reduced cancer risk. Burnt tobacco is well known as a leading cause of cancer worldwide. Oral cancer is related to both intensity and duration of tobacco smoking,18 so e-cigarettes which do not burn tobacco have been thought to be a safe alternative. However, there are concerns about the chemicals in e-cigarettes and the FDA13^,20 even warned against their use because of the presence of toxic chemicals, including di-ethylene glycol and carcinogens, eg tobacco specific N-nitrosamines. Wagener et al suggest this was out of context as the amount of carcinogens in e-cigarettes was detected at only trace levels (0.07–0.2% of that contained in conventional cigarettes) similar to that found in nicotine patches and gum.30

With regards to adverse effects, there is limited data and it is mainly from surveys. The MHRA14 summarizes them as ‘minor’ and including mouth and throat irritation, headache, vertigo and nausea. More serious effects have been rarely reported, including aspiration pneumonia, cardiac arrhythmias and second degree facial burns following explosion of a device.

The significance of passive vaping is at this time unclear, with few studies. Schripp et al studied the effects of passive vaping and concluded that ‘passive vaping must be expected from the consumption of e-cigarettes’.22 Another study concluded that e-cigarettes produced very small exposure compared to burnt tobacco and no apparent risk to human health.21 However, this study was funded by the National Vaper Club in the USA. Further research is clearly needed to investigate the effects of passive vapour and second hand vapour exposure.23

Smoking cessation

E-cigarettes have demonstrated a short-term alleviation of the desire to smoke (burnt tobacco) in a randomized crossover trial.31 Over a longer period of six months, a trial comparing e-cigarettes (16 mg nicotine), nicotine patches and placebo e-cigarettes (no nicotine) found confirmed abstinence rates were 7.3%, 5.8% and 4.1%, respectively. The conclusions were that e-cigarettes, with or without nicotine, were ‘modestly effective’ at helping smokers to quit.32

In smokers who have repeatedly failed in attempts to quit, it has been suggested that e-cigarettes might have a role.33 This could be beneficial in specific patient groups, such as schizophrenia sufferers in whom there is an extremely high prevalence of burnt tobacco smoking. Caponnetto et al showed significant reduction in cigarette consumption in schizophrenic smokers without negative impacts on their symptoms. E-cigarettes might prove a useful tool in psychiatric treatment facilities where smoking bans are particularly challenging to enforce.33

The public health aspects of tobacco control were reviewed at a European workshop where it was concluded that there was much to be done in Europe and globally to address the tobacco epidemic and the need for a paradigm shift within oral healthcare was suggested.34

Smoking cessation services are in an awkward position as significant numbers of people, up to one in three quit attempts,1 are using e-cigarettes to help stop smoking. Cessation services are unable to recommend e-cigarettes as they are unlicensed. A survey of English Stop Smoking Services showed most practitioners were advising that they were unlicensed.35 Recently, an MP attracted media attention by rejecting her local public health team's advice that e-cigarettes should not be used by people who want to stop smoking.36 Current NICE guidance37 recommends the use of licensed nicotine-containing products (NCPs) as part of NRT for harm reduction purposes, but does not currently include e-cigarettes. This is, however, a rapidly changing area and the National Centre for Smoking Cessation and Training (NCSCT) has recently suggested practitioners ‘be open to electronic cigarette use in people keen to try them’.11

The psycho-social impact of e-cigarettes is perhaps one of the biggest areas of concerns. In recent years, conventional smoking has become less socially acceptable, particularly with the introduction of the smoke-free legislation. The concern is that e-cigarettes will re-normalize smoking culture, particularly to the younger generations, and could potentially have gateway effects to conventional smoking. Social media is increasingly being used to target younger audiences.38 Adverts can be glamorous and slick, featuring attractive models completing James Bond-like stunts.39 E-cigarettes are truly a consumer product with a huge range of options available. They can be made to replicate traditional cigarettes (Figure 4) or a more modern ‘pen like’ design and purchased from as little as £1 or as much as £100 (Figure 5).

Potential effects on oral health

Potential oral effects of e-cigarettes are currently unclear. Much of the existing literature examines the effects of smoking burnt tobacco rather than the specific effect of nicotine on oral tissues. The term ‘nicotine’ and ‘smoking tobacco’ are used almost interchangeably in several papers, creating a confusing picture.

Studies have suggested that vaporized nicotine is primarily absorbed by the buccal and pharyngeal mucosa rather than the alveoli due to several factors, including particle size.16^,40 This highlights the potential for vaporized nicotine to have significant effects in the oral cavity.

The oral health risks of tobacco use were reviewed in a consensus report following a European Workshop.41 Tobacco smoke has carcinogenic effects as well as effects on periodontal diseases, tooth loss, implant failure and dental caries. It is well accepted that smoking burnt tobacco increases susceptibility to periodontitis42 and impairs wound healing43 affecting the vascularity, inflammatory response and fibroblast function. What is unknown is if nicotine vaporized in e-cigarettes carries the same risks.

With regards to wound healing, the mechanism for damage by cigarette smoke is thought to be due to the formation of reactive oxygen species. Recently, the role of nicotine in this process has been questioned.44 Systemically, nicotine has been shown to have atherosclerotic effects, while locally nicotine may have positive angiogenic effects. Animal studies have shown an infusion of nicotine reduces peripheral perfusion but increases intestinal and muscular blood flow, while nicotine alone can increase oxygen tension in tissues, the opposite effect to cigarette smoking.45 Nicotine has even been suggested to have a therapeutic effect via transdermal patches with reduced myocardial ischaemia46 and even to facilitate wound healing after surgery.47 A study assessing the effects of topical nicotine, in the form of electronic cigarettes, on blood flow in free flaps in head and neck cancer is already under way.47

The relationship between periodontal diseases and cigarette smoking is well established18 but the role of nicotine is still unclear. The traditional view is that tobacco smoking causes vasoconstriction in gingival tissues,48 with subsequent authors suggesting necrotic lesions like ANUG are caused by nicotine-induced vasoconstriction and stress.49 The exact role of nicotine within gingival tissue perfusion remains unclear and the effects from nicotine are likely to be due to impairment from chronic exposure rather than a simple vasoconstrictive effect from a single smoking episode.50

At a cellular level, the effect of nicotine is likely to be complex and multi-faceted. Nicotine exposure has been linked with impaired osteogenic differentiation in human periodontal ligament stem cells51 and has been shown to affect lipid metabolism in oral epithelial cells. A direct relationship is reported between nicotine and low density lipoprotein receptors in oral epithelial cells and this suggests nicotine might contribute to the development of both cardiovascular and periodontal diseases.52 Nicotine exposure has also been shown to impair fibroblast attachment and collagen synthesis, which may impair the healing response in periodontal disease in smokers.53

Neutrophil bacteriocidal activity is thought to contribute to the damage of gingival tissues and the inflammation seen in periodontal diseases. Neutrophil function can be adversely affected by exposure to tobacco smoke leading to:

The role of nicotine alone is unclear, only being investigated in a handful of studies as detailed in a review paper by Palmer et al.50

Dental implant treatment, particularly guided bone augmentation procedures, could be adversely affected by the wound healing effects of nicotine exposure. In a rat model it was shown that nicotine jeopardized, but did not prevent, the process of guided bone augmentation.54 A laboratory study of rabbit primary osteoblasts exposed to nicotine showed inhibition of both osteoblast proliferation and growth factor expression. The authors concluded that these may have a detrimental effect on the survival rates of dental implants.55

Users of e-cigarettes commonly reported side-effects such as a dry mouth. Further research is needed to determine if this is transient or permanent and clinically relevant. Additionally, a likely positive effect on the hard tissues of the oral cavity will be the reduced staining from the e-cigarette compared to smoked burnt tobacco.

Discussion

Nicotine replacement therapy (NRT) is a well-established care pathway to support smokers wishing to quit. NRT takes many forms such as:

The use of e-cigarettes as a smoking cessation tool is a contentious issue.

UK estimates of e-cigarette users are in the region of 2.1 million, with the majority being made up of current and ex-smokers with a reportedly negligible number being non-smokers.14 Moreover, the use of e-cigarettes by children is reported to have been limited to those who have already tried smoking.56 Figures from a recent survey2 commissioned by ASH (Action on Smoking and Health) show 18% of smokers reported regular e-cigarette usage in 2014, a number that has increased almost 6-fold from 3% in 2010. This coincides with a significant increase in the number of smokers reporting having tried e-cigarettes, from 9% in 2010 to 52% in 2014. It has been suggested that as many as 400,000 (2013 data) people have fully replaced conventional smoking with the use of e-cigarettes.

Most NRTs are licensed by the MHRA and have marketing authorization for use as a smoking cessation tool. E-cigarettes, however, are not, and are currently regulated as a general consumer product. In June 2013, the MHRA announced that they planned to regulate e-cigarettes as medicines available as over-the-counter medicines or for prescription by heathcare professionals.14 In December 2013, the European Parliament superseded this when it rejected proposals to license e-cigarettes as medicines. Jeremy Mean, Group Manager of Vigilance and Risk Management of Medicines at the MHRA is quoted as saying that the EU policy on e-cigarettes is a ‘dog's dinner’.1 In February 2014, an EU Tobacco Products Directive was passed which will regulate e-cigarettes from May 2016. E-cigarettes will be regulated as a tobacco product with several restrictions including:

E-cigarettes with higher concentrations of nicotine (>20 mg/ml), or if manufacturers opt in, will be regulated by the MHRA as over-the-counter medicines.2

The valued health gain for each single successful quit attempt has also been postulated to be in the region of £74,000, meaning that, if 10% of the 1.3 million users of electronic cigarettes (or vapers) in the UK (in 2012) quit successfully, there will be a gross saving of over £7 billion.57 Regulation will have several advantages, including mandatory limits of strength of the nicotine or volume of the nicotine-containing liquid and more rigorous quality control processes ensuring reduced risks from poor manufacturer processes.

There is an alternative argument against regulation, such as that proposed by Matthew Ridley, 5th Viscount Ridley, member of the House of Lords, voiced during a speech at the Lords and subsequent blogs,58 that attracted much attention in ‘vaping’ circles. The thrust of the speech was that ‘medicinal regulation of vaping could kill people’. His argument is that licensing e-cigarettes will lead to increased cost, reduced advertising and decreased glamorization, leading to fewer people attempting to quit smoking by using e-cigarettes. He charismatically discusses the safety arguments given for licensing and suggests that we rely on packaging and common sense for products such as bleach rather than regulating them as medicines. He also likens e-cigarettes to aubergines (that contain small volumes of nicotine) and asks us to consider if they should be regulated as medicines.

Opinions on e-cigarettes are hugely divided. Some have said e-cigarettes are the ‘greatest health advance since vaccinations’ (Professor David Nutt, former government drugs adviser59 and ‘e-cigarettes can be a game changer in the fight against smoking’ (Chris Davies MEP60), whilst others have voiced their concerns about e-cigarettes ‘re-normalizing’ smoking (Mark Drakeford, health minister).61

More recently there have been several papers62^,63^,64 in the medical literature with very positive viewpoints, emphasizing the huge harm reduction potential of e-cigarettes and the growing amount of safety and efficacy data.

E-cigarettes pose a difficult problem with regards to smoke-free legislation. They are not regulated under the smoke-free legislation in the UK at present and several e-cigarette manufacturers promote this as a major advantage of e-cigarettes. There is, however, a growing trend for e-cigarettes to be banned on a local basis, for example on public transport and inside public buildings (Figure 6).

The oral health team has a role in smoking cessation65 and needs to be appropriately trained to deliver in surgery support or undertake specialist referrals. As healthcare professionals we find ourselves in an uncomfortable position when discussing e-cigarettes with patients. It is officially hard to endorse their use as they are currently unlicensed, lacking research and the regulatory agencies (FDA, MHRA) have expressed concerns about safety.

Conclusion

From a general health viewpoint, although there is clearly a significant lack of research, it would appear e-cigarettes are less harmful than burnt tobacco and have the potential to be positive, with harm-reduction effects, if they are used in a similar way to other nicotine replacement therapies. There are concerns regarding the psychosocial impact of e-cigarettes, with the potential for re-normalization of smoking, particularly in younger generations. Also, it mustn't be forgotten that e-cigarettes typically contain nicotine, which is addictive, and have as yet ill-defined biological effects. Of particular interest to dental health professions is the lack of research into the oral effects of e-cigarettes, with specific concerns regarding periodontal disease, surgical wound healing and effects on oral mucosa.

Summary