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E-Cigarette Summit - Dr Lynne Dawkins


So, as Ann said, I’m going to give a basic introduction to e-cigarettes and the various different types. I’m also going to look briefly at the nature of use, and then finally cover some of the research one effectiveness, and all of that will be covered in twenty minutes.


To start with my disclosures, I haven’t received any funding from the tobacco or the pharmaceutical industry although I have received funding for research purposes from the e-cigarette industry.


So I’m going to start by introducing you to e-cigarettes and the various different types. So we’ll start with what’s sometimes known as the first generation types or the cigarette like cigalike e-cigarettes. Now, these cigarettes in this slide obviously all resemble cigarettes in some way or another. E-cigarettes basically are battery operated devices that deliver nicotine via vapour that is inhaled. They involve no tobacco, no combustion, so there’s no smoke, although the vapour that is exhaled sometimes resembles smoking, so for this reason the active using a cigarette is often referred to as vaping.


All e-cigarettes have three basic components; a battery, an atomiser and a cartridge. This is regardless of how they appear. So the battery powers the atomiser to heat up a nicotine containing fluid within the cartridge. Now, the first types of e-cigarettes that became available on the market were these three piece devices, so the atomiser unscrews into the battery and the fluid filled cartridge slipped over the top of the atomiser. Now, these are the ones I saw when I first started researching e-cigarettes in 2009. These have now been replaced by these two piece cartomiser devices, so the atomiser and the cartridge are now combined within one piece and it screws into the battery. The user then can replace the cartridge when the fluid runs out. We also have the disposable e-cigarettes, so these are just simple to use, one piece device, the user takes between 200 and 500 puffs and then throws it away when it runs out. These cigalike devices are all available with various different flavours and various amounts of nicotine, but it’s important to note with these types the user doesn’t come into any contact with the fluid itself.


Moving on then to the so-called second generation type of e-cigarettes, you can see here from some of the examples that these types don’t resemble cigarettes. They tend to be more colourful, bigger batteries, look like pens or screwdrivers in some cases. They still have the three basic components; the battery, the atomiser and the cartridge, but typically the batteries with these devices are much larger, this way they hold their charge for longer and don’t need to be re-charged as frequently. Instead of a cartomiser, these devices tend to have a separate atomiser and a fluid filled cartridge that the user can fill up with bottles of e-liquid and these are sometimes referred to as tanks. We can also see they come with different types of mouth pieces, various different colours, various different designs, so you can really begin to pimp your e-cigarette here. And the various different components, the batteries, the atomisers, the mouthpieces, are all interchangeable so you can mix and match and start to create your own here.


And that then brings me to the so-called third generation e-cigarettes and beyond. Modified e-cigarettes or mods literally refer to something that has been modified. True mods originated from users who would use another device such as a torch or a mint tin, for example, and change that into an electronic cigarette. Manufacturers then started to think, ‘Oh, this is quite a nice idea,’ and began to create their own modified electronic devices. Just like the second generation devices, these devices come with a range of different batteries, atomisers, cartridge, clearomisers, tank systems, so you really can mix and match giving the consumer a huge range of choice here. Now, the rate at which e-cigarette technology is moving is unprecedented. I do struggle to keep up with how quickly things are moving. There’s new devices coming out almost weekly. The atomisers, for example, that are available nowadays bear very little resemblance to the ones that I saw when I started researching e-cigarettes. Battery technology is also evolving; a lot of batteries now come as variable voltage systems so the user can adjust the battery to control the amount of power that is applied to the atomiser, and I’m told that this affects things like vapour production, throat hit, and the general performance of the device. Finally, looking ahead to the next generation devices, a number of models are now coming out that use a slightly different technology where the atomisers are actually immersed within the fluid itself. And the majority of the new batteries that are available now are so-called insert batteries that slip into a metal tube with a control head on the top so the user can actually adjust the settings using a digital display or lights to adjust the settings to his/her e-cigarette. And some even now come with programmable software, so we can see how much these devices have evolved since the simple three piece cigalikes a few years ago.


The next two look at the liquid. E-cigarette liquid is used with the second and the third generation type devices. It contains propylene glycol and/or vegetable glycerine, and these viscose liquids make up about 95% of the e-cigarette liquid or fluid. Propylene glycol is more common. It tends to be thinner than vegetable glycerine which creates more of a noticeable vapour and is generally regarded as sweeter. Almost all e-cigarette liquid contains nicotine although some manufacturers make liquid that doesn’t contain any nicotine, and the amount of nicotine in the fluid is expressed as weight per volume, so milligrams per milliliter, typically ranging from about 0 to 36. Flavourings are also very important. Most common are tobacco, mint and fruit, but with an increasing range of flavours now available. You’ll be surprised at some of the types of flavours that are found. And sometimes additives are also included, for example, to augment throat hit.


E-cigarettes were originated in China and were introduced into the Chinese domestic market in 2004 and were found in Europe around the end of 2006. Sales of e-cigarettes have doubled or trebled every year since then. So, for example, among smokers in the UK in 2010 2.7% were using e-cigarettes and this increased to 6.7% in 2012. And the charity Action on Smoking and Health estimated earlier this year that there are 1.3 million current e-cigarette users. Now, we saw from the previous slides that I showed you that there’s a vast array of e-cigarettes available from the cigalike disposables through to the more sophisticated next generation personal vaporisers. Originally, production occurred exclusively in China but this is now moving outside of china and manufacturing is occurring in the US and the EU as well. We also note, tobacco companies are now also buying into the ecigarette market, as you are all probably well aware, buying out e-cigarette companies or developing their own next generation nicotine delivery devices.


Looking next then at who uses them, findings from seven representative samples of the general population suggest that the proportion of e-cigarette users is somewhere between two and eight times higher in current smokers than in former smokers, so indeed most smokers are smoking and using e-cigarettes, what are sometimes referred to as dual users. There’s little evidence, however, of use in never smokers, only half a percent of never smokers report having tried e-cigarettes, and there are no documented studies showing daily use among never smokers. Compared with non-smokers, e-cigarette users tend to be younger, better educated and on a higher income. Smokers report using e-cigarettes as either a means of completing replacing smoking or partially replacing their smoking or to try and quit smoking altogether.


So, turning next to look at patterns of use in regular users. These findings are taken from an internet survey of regular e-cigarette users who have been using these for an average duration of ten months, quite a long time, noticeably longer than people use nicotine replacement therapy. The first thing to note, I think, here is that most of these regular e-cigarette users are using the so-called second generation devices. Only 18% reported using the cigarette-like first generation devices. The strength of nicotine containing e-liquid most commonly used was 18mg per millilitre. Some like to combine strengths, use different strengths at different times of the day, and very few regular users used the nonnicotine containing e-liquid. Tobacco was the most preferred flavour even in regular users.


So, I’m going to turn next to look at effectiveness, and what do we mean by effectiveness? Well, I’ve broken it down to can e-cigarettes help to reduce tobacco related cravings, are they effective for nicotine delivery, and then finally to help smokers to try and quit.


So, if e-cigarettes are going to be effective at helping smokers to make the switch they really need to address tobacco craving, and a number of studies have looked at cigarette deprived smokers who use the e-cigarettes and then see if it helps to reduce their craving. A couple of studies, one in the US and one in New Zealand both reported that e-cigarettes were associated with a self-reported reduction in craving, but these studies also looked at effects of tobacco smoking and found that cigarette smoking the magnitude of reduction was even greater with cigarette smoking. In a study of 86 tobacco deprived smokers that used a first generation three piece cigalike device in our lab, we noted that after five minutes there was a reduction in craving but we observed this in both the nicotine containing e-cigarette and the non-nicotine containing e-cigarette. After twenty minutes of further reduction was observed in the nicotine e-cigarette. So, quite interesting, it might suggest that for these smokers that just the active using the e-cigarette regardless of the nicotine intake at least initially might be important to help reduce craving.


So, looking at nicotine delivery next. Two early studies, and I say early, 2010 is early in the e-cigarette literature, two early studies showed that e-cigarettes were pretty ineffective at delivering nicotine, so the first study by Chris Bullen and colleagues compared the 0mg and the 16mg nicotine e-cigarette with Nicorette inhalator and with tobacco smoking. The e-cigarette was only able to achieve an increase in blood nicotine levels up to 1.3 nanograms were millilitre and that took twenty minutes. This was comparable with that seen in the Nicorette inhalator. By contrast, levels seen with tobacco smoking were ten times higher than that. Similar results found by Eissenberg who compared two different brands of e-cigarettes and, again, reported that only tobacco smoking was able to significantly raise blood nicotine levels. Now, more recent evidence suggests that the very low levels achieved here might be because these were smokers who had not used an e-cigarette before and were therefore not using it optimally for nicotine delivery. There’s a difference between the way somebody smokes a tobacco cigarette and puffs on an electronic cigarette. Or it could be that these early studies were using those three piece cigalike first generation type devices and we know that things have moved on quite a lot since then.


So, more recently, Vansickel and Eissenberg recruited eight regular e-cigarette users who were all using their own second generation devices and they all used their own strength of nicotine containing fluid. Vansickel and Eissenberg looked at levels of blood nicotine delivery after ten puffs and then throughout a subsequent sixty minute ad-lib puffing period, and we could see here that there was a significant elevation in levels of blood nicotine after ten puffs, and this then increased gradually over the next sixty minute of ad-lib puffing.


Not clear from this whether this is due to the device itself, the second generation device, or if this is due to user experience. So we replicated this study; we used exactly the same methodology, experienced users they took ten puffs and then used it ad-lib for the next sixty minutes. The difference was these participants all used cigalike cartomiser like device, a standard 18mg per millilitre device. The blue line here shows you the mean so you can see after five minutes there was a significant increase in blood nicotine levels. Again, like in the previous study, this continued to rise throughout the ad-lib puffing period. What’s particularly notable about this and the previous study is the marked individual variation that we’re seeing in nicotine delivery, so I’ve plotted the person with the lowest and the person with the highest nicotine delivery. They all use the same device, they all had ten puffs here. This person is barely achieving 3 nanograms per millilitre. This person is achieving a whopping great 25 nanograms per millilitre. So it indicates to us that individual vaping technique is quite important when it comes to nicotine delivery and perhaps that individuals can titrate with e-cigarettes like they can with cigarettes which might contribute to their appeal.


Moving on next to look at effects of e-cigarette use on patterns of smoking behaviour, so starting with survey studies. A number of surveys have been conducted now, about fifteen in total, and they generally report high self-reported quite rates. So, for example, in our study 74% reported that they hadn’t smoked at least for a few weeks since they started using e-cigarettes. A further 14% said it had dramatically reduced their cigarette consumption. Similarly, Etter and Bullen, 92% of e-cigarette users said it had helped them to reduce their smoking, 96% of those who were ex-smokers said it had helped them to stop smoking. Just a note of caution about these survey type designs. The samples are self-selecting, we can’t control who takes part, these are likely to be e-cigarette users who have been successful at adopting the e-cigarette and might want to present it in a more favourable light, so perhaps we are seeing over-estimates of quit rates here.


An example of a few other studies. In a survey of over 200 smokers who had purchased an e-cigarette, Siegel and Colleagues looked at abstinent rates at six months; 31% reported, although this wasn’t verified, that they were abstinent after six months. And, interestingly, in those who used the e-cigarette more intensively i.e. more than 20 times a day, quit rates were even higher. And Polosa and Colleagues conducted a prospective study of 40 smokers and found that 55% of these had either stopped smoking completely or had cut their cigarette consumption by half, and there were in smokers not willing to quit at six months.


Finally, really to address the question of whether e-cigarettes are effective at helping smokers to stop smoking, we want to adopt randomised controlled trials. These are generally seen to be the gold standard in smoking cessation research. But a note of caution here, applied to e-cigarettes I think this is a little bit more complicated. We are looking at a rapidly evolving industry here and randomised controlled trials are very time consuming, so it’s likely that by the time the results are published the device that was used may not currently be available or is not what is currently being used. So the findings become outdated quite quickly. Nevertheless, we have results from two such surveys, the first by Caponnetto and Colleagues in Italy; 300 smokers were randomised through the two different strength nicotine e-cigarettes or a no-nicotine e-cigarette, and abstinence rates at one year were 13% in those given the 7.2mg e-cigarette. And in the only randomised controlled trial of treatment seeking smokers in New Zealand, Bullen and Colleagues randomly allocated a large number, 657 participants, to a nicotine e-cigarette nicotine patch or a non-nicotine e-cigarette and you can see the six months abstinence rates there; 7.3% versus 5.8% receiving nicotine e-cigarette versus patch. These are quite low levels actually for a randomised controlled trial, possibly reflecting lack of behavioural support in this study. However, what we can say is that the e-cigarette in this study was at least as effective as currently available nicotine patch. As I said, the devices used in both these studies were available in 2009/2010, were three piece cartomiser devices, not cartomiser, sorry, the three piece early ciga-like devices that are now obsolete and are known to deliver low levels of nicotine. So it’s likely that if we repeated such studies using a second generation device we would see higher levels than this, I think.


Okay, so to conclude and summarise, e-cigarettes deliver nicotine via an inhaled vapour. There’s an increasing range of products available now from the simple disposable cigalikes through to the next generation personal vaporisers. They are used by smokers who report they want to quit or to replace their cigarette smoking either partially or fully and they are used with increasing popularity. There are no signs of e-cigarette sales slowing down. We’ve seen that they are moderately effective at alleviating tobacco craving and that they can deliver nicotine at least in habitual users anyway. Randomised controlled trials show cessation rates at least comparable perhaps exceeding those of NIT but as yet no randomised controlled trials have explored the second or third generation type devices. Thank you. [Applause]

Chair: Okay, thank you very much indeed, Lynne, for an excellent overview of the vast amount of literature in a very fast moving evidence base. We’ll move straight on as Lynne took up her allotted time.

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