Monaldi Arch Chest Dis
`2013; 79: 1, 12-19
`
`REVIEW
`
`Electronic cigarette: a possible
`substitute for cigarette dependence
`P. Caponnetto1,2, C. Russo1,2, C.M. Bruno2, A. Alamo1,2,
`M.D. Amaradio1,2, R. Polosa1,2
`
`ABSTRACT: Electronic cigarette: a possible substitute for
`cigarette dependence. P. Caponnetto, C. Russo, C.M. Bruno,
`A. Alamo, M.D. Amaradio, R. Polosa.
`Cigarette smoking is the leading cause of premature
`mortality in western countries and it is important for smok-
`ers to stop as early as possible. Electronic cigarettes are a
`popular phenomenon of global proportion. Recent uncon-
`trolled studies, reported that a certain number of smokers
`have quit using electronic cigarettes. This could hint a role
`
`for electronic cigarettes to be used for smoking cessation,
`and therefore merits further evaluation for this purpose.
`Besides vaporising nicotine to be inhaled, electronic ciga-
`rettes may also provide a coping mechanism for condi-
`tioned smoking cues by replacing some of the rituals associ-
`ated with smoking gestures, and for these reasons cigarette
`could become a tool – if studied more extensively – in the
`fight against tobacco-related morbidity and mortality.
`Monaldi Arch Chest Dis 2013; 79: 1, 12-19.
`
`Keywords: Nicotine addiction, Smoking cessation, Smoking reduction, Electronic cigarettes, Tobacco harm reduction.
`
`1 Centro per la Prevenzione e Cura del Tabagismo (CPCT), Azienda Ospedaliero-Universitaria “Policlinico V. Emanuele”,
`Università di Catania, Catania;
`2 Institute of Internal Medicine, Azienda Ospedaliero-Universitaria “Policlinico V. Emanuele”, Università di Catania, Catania,
`Italy.
`
`Correspondence: Prof. Riccardo Polosa, MD, PhD, UOC di Medicina Interna, Edificio 4, Piano 3, AOU “Policlinico V. Emanuele”,
`Università di Catania, Via S. Sofia 78, 95123 Catania, Italy; e-mail: polosa@unict.it
`
`Introduction
`
`Tobacco addiction is the leading cause of pre-
`ventable premature mortality across the globe with
`approximately 5 million tobacco-related deaths per
`annum [1]. Death is principally caused by cancers,
`chronic obstructive pulmonary disease (COPD),
`lung and ischemic heart disease (IHD) [2, 3]. De-
`pending on the different diseases, short and long
`term abstinence is known to decrease significantly
`the peril of these diseases [3, 4].
`Contemporary strategies to encourage smok-
`ing cessation range from simple medical advice to
`pharmacotherapy and counselling [5]. Counselling
`and drugs are effective when used by themselves
`for treating tobacco addiction, but the combination
`of counselling and medication is more effective
`than either alone [5]. Consequently, clinicians
`should encourage all smokers attempting to quit to
`use both counselling and medication. It should be
`noted that treatments aimed at smoking cessation
`are among the most cost effective interventions in
`health care [6].The potent addictive qualities of
`nicotine produce a huge hurdle, even for those
`with a real wish to quit smoking. Approximately
`80% of smokers who attempt to quit on their own
`relapse within the first month of cessation, and on-
`ly about 3-5% remain abstinent at 24 week [7].
`Additionally, smoking cessation medications cur-
`rently available such as nicotine replacement ther-
`apy, the atypical antidepressant bupropion and the
`
`partial agonist of the α′ 4β2 nicotinic acetylcholine
`receptor, varenicline, at best double or triple this
`quit rate under the ideal circumstances of a re-
`search setting but have had low uptake and inferi-
`or efficacy in a real life setting [5, 8]. Moreover,
`bupropion and varenicline have come under in-
`creased scrutiny due to reports of serious adverse
`events that include behaviour alteration, depres-
`sion, self-injurious thoughts, and suicidal behav-
`iour [9]. The Tobacco Advisory Group of the Roy-
`al College of Physicians acknowledges that the ad-
`vance of addiction includes modifications in be-
`haviour together with changes in mind, structure
`and function that harm the capacity to achieve and
`sustain abstinence. They note that some of these
`changes may not be completely reversible [10]. Fi-
`nally, even tobacco control policies – particularly
`when not integrated and supported by adequate
`funding – are not very effective [11].
`Consequently, there are 5 million tobacco-re-
`lated deaths per annum. Many smokers will keep
`smoking until they die from it because when given
`only the options of smoking or completely giving
`up nicotine, many will not give it up. Nicotine per
`se does not cause much risk when separated from
`inhaling cigarette smoke, it is important to consid-
`er that another choice is also presented to smokers;
`the reduction of smoking-related diseases by as-
`suming nicotine in a low risk form.
`A new approach is needed; can electronic cig-
`arette be a possible solution? The electronic ciga-
`
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`ELECTRONIC CIGARETTE: A PROMISING TOOL?
`
`rette is a cigarette shaped electronic creation, pro-
`duced and marketed by numerous companies,
`powered by a lithium-ion re-chargeable battery
`that is designed to vaporise nicotine to be inhaled
`[12]. Besides vaporising nicotine to be inhaled,
`electronic cigarettes may also provide a coping
`mechanism for conditioned smoking cues by re-
`placing some of the rituals associated with smok-
`ing gestures (e.g. hand-to-mouth action of smok-
`ing), and for these reasons it is now perceived by
`users as a potentially more attractive substitute for
`smoking than low toxin smokeless tobacco [13].
`Electronic cigarettes use the process of vaporisa-
`tion rather than combustion and for this reason this
`tool could be used as a lower risk substitute for tra-
`ditional cigarettes because tobacco combustion is
`not necessary for its operation. Additionally,
`smokers report buying electronic cigarettes to help
`quit smoking traditional cigarette, to reduce ciga-
`rette consumption, to alleviate nicotine withdraw-
`al symptoms due to workplace smoking restric-
`tions, and to continue having a ‘smoking’ experi-
`ence, but with reduced health risks [14]. Electron-
`ic cigarette is a popular phenomenon of global pro-
`portion [15] that calls for further research, legisla-
`tion, and product development.
`The focus of the present article is about the
`health effects of using an electronic cigarette, with
`consideration given to the acceptability, safety and
`effectiveness of this product to serve as a long-
`term substitute for smoking or as a tool for smok-
`ing cessation.
`
`Electronic cigarette:
`a rapidly growing phenomenon
`
`Nicotine Replacement Therapy (NRT), the
`most frequent smoking-cessation product, aimed
`at aiding smoking cessation by reducing the sever-
`ity of smoking withdrawal symptoms and ciga-
`rettes cravings, do not fully control all the symp-
`toms of withdrawal because the available delivery
`systems do not reproduce the rapid and high levels
`of nicotine achieved through cigarette use [16, 17].
`Different types of NRT (nicotine lozenge, gum,
`patch, nasal spray, and inhaler) could have a dis-
`tinct role upon either withdrawal symptoms or
`urges to smoke, but there is little direct evidence
`that one nicotine product is more effective than an-
`other. However, it is possible that electronic-ciga-
`rettes, that resemble a traditional cigarette may de-
`liver aerosolised nicotine in a more efficient man-
`ner. Moreover, efficacy with NRTs, as with other
`anti-smoking medication, is modest because it ad-
`dresses only the physical component of cigarette
`smoking (i.e. nicotine dependence), and is unlike-
`ly to resolve the psychological factors (cognitive
`and behavioural including handling, holding and
`puffing a cigarette) associated with cigarette
`smoking [18, 19]. When the smoker quits, those
`rituals are no longer there, but the need for the rit-
`ual still exists. Given that both nicotine and smok-
`ing related cues appear to control cigarette craving
`and withdrawal symptoms, electronic cigarettes
`– by supplying nicotine and by mimicking the ritu-
`
`als associated with cigarette smoking – may be used
`as an efficient smoking cessation appliance [20].
`In two studies we have reported objective mea-
`sures of long term smoking cessation in five heavy
`smokers with high nicotine dependence with and
`without major depression, who quit after taking up
`an electronic cigarette. These heavy smokers who
`were treated before for smoking cessation, used e-
`cigarettes on their own and reported during a fol-
`low-up telephone interview to have quit smoking.
`Following this telephone call, all cases were ad-
`mitted to our smoking cessation clinic to assess
`their exhaled-CO measured [21, 22]. This is im-
`portant in consideration of the fact that this was ac-
`complished without the use of recommended nico-
`tine dependence treatments and smoking cessation
`counselling, and who had repeatedly failed in pre-
`vious attempts when provided with professional
`smoking cessation assistance at our smoking ces-
`sation clinic. In a recent research, we observed
`possible change in smoking habits of 40 smokers
`not willing to quit using an electronic cigarette
`[23]. Combined six months smoking abstinence
`and smoking reduction was shown in 22/40 (55%)
`smokers. The fact that 22 smokers unwilling to
`quit eventually switched to the electronic cigarette
`or quit altogether for 6 months needs to be ex-
`plained. Although the results presented are encour-
`aging, large and carefully conducted prospective
`randomised controlled trials will be required be-
`fore a definite answer about the efficacy and safe-
`ty of electronic-cigarettes can be reached. Some
`research is already in progress in Italy and New
`Zealand and hopefully it will be able to confirm
`and expand the preliminary clinical knowledge of
`electronic-cigarettes.
`
`Health analysis about electronic cigarettes
`
`Toxicology
`
`Complete toxicology characterisation of the el-
`ements contained in electronic cigarettes’ liquid
`and vapour using gas chromatography mass spec-
`trometry (GC-MS) is accumulating quickly and
`shows that their primary components are propy-
`lene glycol (PG), water, nicotine and glycerine
`[24]. PG is approved by Food and Drug Adminis-
`tration (FDA) for a variety of pharmaceuticals for-
`mulation. It has undergone extensive testing and is
`widely used in a variety of consumer products in-
`cluding food [25].
`In a classic study, Laugesen tested electronic
`cigarette mist for over 50 priority-listed cigarette
`smoke toxicants and found none [26]. This re-
`search only revealed minimal traces of Tobacco-
`specific Nitrosamines (TSNAs) in the “high” nico-
`tine cartridge of a Ruyan brand electronic cigarette
`similar to the quantity reported to be present in a
`nicotine medicinal patch.
`In an recent report, laboratory analyses carried
`out by the US Food and Drug Administration
`(FDA) failed to find carcinogens and toxic chemi-
`cals in most of the electronic cigarettes tested with
`a single exception: about 1% of diethylene glycol
`
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`P. CAPONNETTO ET AL.
`
`(DEG) were detected in the liquid of one of the 18
`samples, however this not represent a toxic quanti-
`ty [24, 25].
`Another independent analysis of the same
`electronic cigarette products tested by the FDA
`found no evidence of carcinogenic TSNAs in their
`aerosol [27]. The fact, highlighted by FDA, that
`there is no quality control in the making of several
`E-cigarettes can be a cause for different findings in
`different analyses of the same product.
`A further study conducted by Cahn and Siegel
`have reviewed the evidence regarding the safety of
`the liquid in electronic cigarettes [28]. TSNAs
`were reported in two studies, but at trace levels,
`similar to those found in a nicotine patch, were
`most importantly, about 500-fold to 1400-fold
`lower than TSNA levels measured in regular ciga-
`rettes (electronic cigarettes containing only 0.07-
`0.2% of the TSNAs present in tobacco cigarettes)
`(table 1). This is an important factor. Electronic
`cigarettes deliver a nicotine vapour without the
`combustion products that is responsible for nearly
`all of smoking’s harmful effects. Temperatures of
`up to 950 degrees are generated with each puff of
`a lit cigarette and some 5000 or so chemicals,
`many of which are toxic or carcinogenic, are gen-
`erated during the combustion process [29]. Elec-
`tronic cigarettes use the process of vaporisation
`rather than combustion and the low operating tem-
`perature of the atomiser (about 50-60°C; approx.
`5-10% of the temperature of a lit cigarette) sug-
`gests that these products as a class are unlikely to
`emit cigarette toxicants in their mist [25].
`
`General safety data
`
`In a recent study on safety assessment of elec-
`tronic cigarettes smokers, researchers found no ab-
`normal changes in blood pressure, haematological
`data, or blood chemistry and no severe adverse
`
`events after 4 weeks of regular electronic ciga-
`rettes use [30]. Our clinical safety assessment of
`electronic cigarette in 40 smokers showed that dry
`cough, mouth and throat irritation were commonly
`reported in the initial four weeks of use, but all ap-
`peared to wane spontaneously by the end of the
`study, after 24 weeks of regular use [23] (figure 1).
`These are likely to be due to exposure to propylene
`glycol mist generated by the electronic cigarettes’s
`atomizer. Exposure to propylene glycol mist may
`occur from smoke generators in discotheques, the-
`atres, and aviation emergency training and is
`known to cause ocular, mouth, throat, upper air-
`way irritation and cough [31, 32]. Dizziness was
`frequently reported by smokers at the beginning of
`the research and can be brought about by the hy-
`perventilation associated to the greater puffing
`time with the electronic cigarette. The consider-
`able reduction in the occurrence of dizziness ob-
`served by the end of the study may be due to the
`improved familiarisation with the puffing tech-
`nique.
`Additionally, traditional cigarette smoking re-
`duction by mean the electronic cigarette under
`study led to an important decrease in exhaled car-
`bon monoxide (CO) levels [23].
`Surprisingly, typical cigarette withdrawal
`symptoms were not reported during the course of
`the research. It is probable that the electronic ciga-
`rette by providing a coping mechanism for condi-
`tioned smoking cues could alleviate typical ciga-
`rette withdrawal symptoms associated with ciga-
`rette smoking reduction and cigarette smoking ab-
`stinence as shown for nicotine-free inhalators [33].
`In a recent study Vardavas et al [34], conclud-
`ed that: “Electronic Cigarette assessed in the con-
`text of this study were found to have immediate ad-
`verse physiologic effects after short term use that
`are similar to some of the effects seen with tobac-
`co smoking, however the long term health effects
`
`Table 1. - Summary data of maximum tobacco-specific nitrosamine levels in various cigarettes and nicotine-
`delivery products including electronic cigarettes (ng/g, except for nicotine gum and patch that are ng/gum piece
`and ng/patch) [Modified by Chan Z et al. J Public Health Policy 2011]
`
`Product
`
`Nicorette gum (4 mg)
`
`NicoDerm CQ patch (4 mg)
`
`Electronic cigarettes
`
`Swedish snus
`
`Winston (full)
`
`Marlboro (full)
`
`Camel (full)
`
`Marlboro (ultra-light)
`
`NNN
`
`2.00
`
`ND
`
`3.87
`
`980.00
`
`2200.00
`
`2900.00
`
`2500.00
`
`2900.00
`
`NNK
`
`ND
`
`8.00
`
`1.46
`
`180.00
`
`580.00
`
`960.00
`
`900.00
`
`750.00
`
`NAT
`
`ND
`
`ND
`
`2.16
`
`790.00
`
`560.00
`
`2300.00
`
`1700.00
`
`1100.00
`
`NAB
`
`ND
`
`ND
`
`0.69
`
`60.00
`
`25.00
`
`100.00
`
`91.00
`
`58.00
`
`NNN = 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NNK = N’-nitrosonornicotine; NAT = N’-nitrosoanatabine; NAB =
`N’-nitrosoanabasine; ND = Not detected.
`
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`ELECTRONIC CIGARETTE: A PROMISING TOOL?
`
`The role of nicotine
`
`Fig. 1. - Adverse events reported by electronic cigarette users who completed all study visits
`[Modified from ref. 23].
`
`Nicotine fulfils all the
`criteria of an addictive agent,
`including psycho-active ef-
`fects, compulsive use, relapse
`after abstinence, drug-rein-
`forced behaviour, physical
`dependence and tolerance.
`Nicotine stimulates dedicated
`receptors in the brain which
`create both sedative and eu-
`phoric effects [38]. Individu-
`als who have mood dysfunc-
`tions or attention deficits are
`more likely to start smoking
`and less likely to be able to
`stop smoking. Nicotine has
`useful effects on attention,
`concentration, and mood and
`smokers who have mood
`dysfunctions or attention
`deficits may be depending on
`nicotine as a means of self-
`medication [39].
`Nicotine is a sympath-
`omimetic drug that releases
`catecholamine, increases heart rate and cardiac
`contractility, constricts cutaneous and coronary
`blood vessels, and transiently increases blood
`pressure. It also reduces sensitivity to insulin and
`may aggravate or precipitate diabetes, and may
`contribute to endothelial dysfunction. These vari-
`ous effects on the cardiovascular system could, in
`theory, promote atherogenesis and precipitate
`acute ischemic events in people who have coro-
`nary artery disease. This has been of particular
`concern in smokers who use nicotine medication
`while they are still smoking. However, increased
`cardiovascular risk due to nicotine medication
`does not appear to be a problem [40]. Nicotine is
`not a direct carcinogen, but there are concerns that
`it may be a tumour promoter. Whether nicotine is
`a cancer promoter in people has not been estab-
`lished [40]. Suspected adverse reproductive effects
`of nicotine include most prominently fetal neu-
`roteratogenic effects. In general, it is not desirable
`to use nicotine during pregnancy, but if the alter-
`native is cigarette smoking, then nicotine medica-
`tion is less hazardous [40]. Nicotine replacement
`therapy used long term is well-tolerated without
`evidence of serious adverse health effects [41]. In
`conclusion, nicotine per se does not cause much
`risk when separated from inhaling smoke.
`
`Effect of an electronic nicotine delivery device
`(e-cigarette) on smoking habits
`
`Contemporary smoking cessation treatments
`can increase the chance of quitting in committed
`smokers who are already motivated and prepared
`to stop smoking [42], but a broader range of strate-
`gies are needed in order to bring more smokers in-
`to treatment and increase the numbers who are mo-
`tivated to make quit attempts. Although not for-
`
`15
`
`of e-cigarette use are unknown but potentially ad-
`verse and worthy of further investigation”.
`Unfortunately, the work illustrated by Var-
`davas and colleagues [34] are not conclusive due
`to the number of subjects studied (30 cases and 10
`controls) and, the choice of study outcomes of un-
`clear clinical relevance.
`The reported 16% decrease in FeNO (i.e. 2.1
`ppb in absolute term) and 11% increase in periph-
`eral flow resistance (IOS) (i.e. 0.025 kPa/L/s in ab-
`solute term) after e-cigarette use from baseline are
`so small and well within tests variability [35, 36]
`that it is highly unlikely to have meaningful ad-
`verse effects. It should be notedthat no changes
`were detected by canonical pulmonary function
`testing after e-cigarette use. Moreover, the small
`changes in FeNO and IOS may be non-specific.
`The mist generated by the e-cigarette per se might
`have contributed to these changes. Nebulization of
`saline per se can reduce FeNO from baseline. Con-
`sequently, authors should have included a more
`pertinent control (e.g. saline mist generated by an
`ultrasonic nebulizer) in their study. Also, another
`reasonable comparator that should have been used
`as control could have been the participants’ own
`brand cigarette.
`The data noted above suggests that electronic
`cigarettes are safer than tobacco cigarettes [28]
`and comparable in terms of tobacco-specific ni-
`trosamines (TSNAs) levels to conventional nico-
`tine replacement products [37]. Despite these im-
`portant results, large and well conducted long-term
`studies will be required before a complete answer
`regarding the safety of electronic cigarettes can be
`formulated [20]. In fact, this tool appears to be
`much safer than traditional cigarettes and compa-
`rable in toxicity to conventional nicotine replace-
`ment products [28].
`
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`P. CAPONNETTO ET AL.
`
`mally regulated as a pharmaceutical product, the
`preliminary positive results with electronic ciga-
`rettes could be confirmed and expanded in classic
`smoking cessation trials of smokers motivated to
`quit.
`The most frequent smoking-cessation treat-
`ment is nicotine replacement therapy, which is
`aimed at addressing nicotine dependence [43].
`NRT does not completely control all symptoms of
`withdrawal because the available delivery systems
`do not reproduce the rapid and high levels of nico-
`tine achieved through tobacco use [16, 17]. Its
`principal mechanism of action is to replace partial-
`ly the nicotine formerly obtained from cigarette
`smoking, and this aids smoking cessation by atten-
`uating the reinforcing effects of nicotine delivered
`via tobacco, and therefore reduces the severity of
`cigarette withdrawal symptoms and cravings [44].
`Nicotine lozenge, nicotine gum, nicotine patch,
`nicotine nasal spray, and nicotine inhaler could
`have a distinct impact upon either withdrawal
`symptoms or urges to smoke, but there is little di-
`rect evidence that one NRT product is more effec-
`tive than another, perhaps with the only exception
`of the nicotine nasal spray [5]. It is possible that
`the electronic cigarette may deliver aerosolised
`nicotine in a more efficient manner compared to
`NRT. Moreover, efficacy with NRT, as for other
`antismoking medications like bupropion or vareni-
`cline, is modest because it addresses only the phys-
`ical component of smoking (i.e. nicotine depen-
`dence), and is unlikely to resolve the psychologi-
`cal factors (cognitive, and behavioural including
`handling, holding and puffing a cigarette) associat-
`ed with cigarette smoking [18, 19]. When the
`smoker quit, those rituals are no longer there, but
`the need for the ritual still exists and this is an im-
`portant cause of early relapse. Given that both
`smoking related cues and nicotine appear to con-
`trol withdrawal symptoms and cigarette craving,
`electronic cigarettes – by supplying nicotine and
`by mimicking the rituals associated with tradition-
`al cigarette smoking – may be used as an helpful
`smoking cessation device [21-23]. Also, when we
`bear in mind that nicotine per se does not cause
`much risk when separated from inhaling cigarettes
`smoke, switching to the electronic cigarette
`equates to quitting in exposure terms.
`An internet survey, conducted by Etter and
`Bullen, supports the idea that electronic cigarettes
`may be effective in smoking cessation. In this sur-
`vey of 3587 electronic cigarettes users [45], most
`respondents (up to 96%) reported the electronic
`cigarette helped them quit smoking or reduce their
`smoking. They also said electronic cigarettes were
`used to avoid relapse. Most ex-smokers in the sam-
`ple (79%) feared they might relapse to smoking if
`they stopped using the electronic cigarette.
`A second online survey [46] enrolled 303
`users, most of whom lived in the US (72%) or Eu-
`rope (21%), via email and links on various blogs
`and forums. This survey was conducted by a UK
`electronic cigarette company and the data was
`evaluated by independent university researchers.
`Most (79%) were using electronic cigarettes as a
`
`16
`
`complete replacement for smoking, with another
`17% using them as a partial replacement. Health
`improvements were reported for general health
`(91%), smoker’s cough (97%), and ability to exer-
`cise (84%), and none reported that these were
`worse.
`In a third survey [47], the 6-month point preva-
`lence of smoking abstinence among the 222 elec-
`tronic cigarettes users was of 31%. Of those using
`the electronic cigarette more than 20 times per day,
`70% were non-smokers at 6 months.
`A further research [48] surveyed 257 users in
`Poland to investigate patterns of use. Of the 170
`users who completed the survey, 83% were regular
`smokers when they began using electronic ciga-
`rettes, and 66% declared they were not smoking.
`Almost all (98%) used their electronic cigarettes
`every day. Nicotine levels used ranged from zero
`nicotine (3%) to higher than 16 mg per cartridge
`(25%), with 41% using 8-16 mg per cartridge.
`These studies, showed that a certain number of
`smokers quit using electronic cigarettes and there-
`fore merits further evaluation for this purpose.
`
`Electronic cigarette and its role in the fight against
`tobacco-related morbidity and mortality
`
`When given only the options of smoking ciga-
`rettes or completely giving up nicotine, many
`smokers will not give it up and will keep on smok-
`ing thus exposing themselves to increasing health
`risks. However, if it considered that nicotine per se
`does not cause much risk, a third possible option is
`also presented to smokers; the reduction of smok-
`ing-related diseases by taking nicotine in a low
`risk form. Tobacco Harm reduction (THR), the
`substitution of low risk nicotine products for ciga-
`rette smoking, is likely to offer huge public health
`benefits. Harm reduction is particularly com-
`pelling for the use of nicotine because so many
`people have such a strong inclination for using it.
`Actually THR is perhaps the most complex, con-
`troversial and divisive issue in tobacco control to-
`day [49].
`As well the realistic example of Swedish snus
`(a type of finely ground moist snuff that delivers
`significant levels of nicotine) as a successful THR
`strategy [50-52], electronic cigarettes may prove to
`be an even more attractive long-term alternative be-
`cause of their similarities to traditional cigarettes
`smoking, including the hand-to-mouth repetitive
`motion and the visual cue of a smoke-like vapour.
`However, electronic cigarettes need to be im-
`proved for different reasons like its heaviness
`compared to classic cigarette and battery recharge.
`Of course, these products may contribute to
`nicotine dependence, but the desire of a cigarette
`– free world is just that – a dream. This is because
`of the established nicotine’s beneficial effects,
`such as the improved ability to pay attention, con-
`centrate and remember, as well as the capacity of
`relieving symptoms of mood impairments [36].
`Several studies [45, 46, 53] paint a profile of
`the typical electronic cigarettes consumer as a
`long-term smoker who tried repeatedly to quit.
`
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`ELECTRONIC CIGARETTE: A PROMISING TOOL?
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`The median age of respondents ranges from late
`30s to mid 40s. The percentage of respondents us-
`ing electronic cigarette as a complete replacement
`for traditional cigarettes smoking ranges from 31%
`to over 79%. Most who did not stop smoking com-
`pletely reduced the number of cigarettes smoked.
`Over 90% reported that their health status had im-
`proved. When asked the main reason why they
`chose to use an electronic cigarette, 64.6% stated
`“to continue to have a ‘smoking’ experience, but
`with reduced health risks”.
`Although much more long term studies are
`needed, early results indicate that electronic ciga-
`rettes could be effective for helping long-term,
`heavy smokers to abstain from inhaling smoke.
`
`Conclusions
`
`According to the World Health Organisation
`(WHO) Framework Convention on Tobacco Con-
`trol (FCTC) a significant reduction in the health
`burden of tobacco in the medium term may be ob-
`tained by encouraging cessation among smokers
`[54]. Therefore, a broader range of strategies are
`needed in order to fight against tobacco-related
`morbidity and mortality.
`Unfortunately, efficacy of evidence based
`smoking cessation treatments is modest and far
`too many smokers are unwilling or unable to quit.
`Electronic cigarettes, for its specific characteris-
`tics, could be used as a lower risk substitute for to-
`bacco cigarettes. This tool may prove to be a
`hopeful solution for reduction in the use of tradi-
`tional cigarettes and their related risk, with the
`
`Table 2. - Positive and negative aspects of e-cigarettes
`
`pros of these products clearly outweighing the
`cons (table 2).
`This electronic device delivers a nicotine vapour
`without the combustion products that are responsible
`for nearly all of smoking’s harmful effects. It use the
`process of vaporisation rather than combustion and
`the low operating temperature of the atomizer (less
`than 80°C) suggests that this tool are unlikely to
`emit cigarette toxicants [25]. In contrast, tempera-
`tures of up to 950 degrees are generated with each
`puff of a lit cigarette and some 5000 or so chemi-
`cals, many of which are toxic or carcinogenic, are
`generated during the combustion process [29].
`Although the reduction in health risks for peo-
`ple who use electronic cigarettes has not been
`quantified, we estimate it as similar to that report-
`ed for smokeless tobacco, which has approximate-
`ly 1% of the death risk of smoking [55]. E-ciga-
`rettes may contain nicotine, which contributes to
`cigarette addiction and helps sustain tobacco use.
`However, if many smokers, not willing to quit, can
`convey their cigarette dependence to a less-harm-
`ful delivery method, millions of live could be
`saved around the world.
`Clearly, these tools need to be effectively reg-
`ulated, but thus far, there have been diverse regu-
`latory responses ranging from no regulation to
`complete bans. WHO’s Study Group on Tobacco
`Product Regulation advised a precautionary ap-
`proach to electronic cigarettes [56] and, with a
`small number of exceptions, most national regula-
`tory agencies have also adopted an analogous ap-
`proach. The experimental basis for this regulatory
`approach is vague, and more appropriate research
`
`Positive
`
`Negative
`
`Beneficial effects on health
`(improved breathing and less cough)
`
`Small percent of the population is sensitive
`to propylene glycol (dry mouth and throat)
`
`No tobacco smoke odour or bad breath
`
`Some flavours (e.g. piña colada) have a lingering fragrance
`
`Less toxic than tobacco smoke
`
`Trace amounts of TSNAs present in some formulas
`
`Mimics sensation in the throat of inhaling smoke
`
`The gestures or actions similar to smoking
`
`Facilitates smoking abstinence
`
`Throat sensation dependent on hardware used
`and liquid composition
`
`Equipment is heavier than traditional cigarette
`and puffing technique requires some training
`
`Some users only manage to reduce the number
`of cigarettes smoked
`
`Relieves withdrawal symptoms and craving
`for tobacco
`
`Relief of withdrawal symptoms varies, affected by quality
`of equipment and nicotine strength of liquid
`
`By and large, no risk to bystanders
`Can be used everywhere
`
`Due to few studies on potential risk to bystanders,
`some communities are outlawing indoor use
`
`No ash, dirt, or burned clothes
`
`Environmental concern about safe disposal
`of cartridges and batteries
`
`Accessible prices (in the long run cheaper
`than traditional cigarette)
`
`The intricacies of their use and maintenance
`may hinder widespread adoption
`
`17
`
`IPR2015-01299
`Fontem Ex. 2004, Page 6 of 8
`
`

`
`on electronic cigarettes must be conducted in order
`to ensure that the decisions of regulators, health-
`care providers and consumers are based on evi-
`dence based medicine.
`In the absence of specific evidence, it is im-
`portant that currently marketed electronic ciga-
`rettes must comply with the best possible quality
`standards. For example, regulations should ensure
`that the liquid is manufactured under sanitary con-
`ditions and uses pharmaceutical grade or USP
`grade ingredients, and that a listing of all ingredi-
`ents and information on the percent of nicotine
`present, if any, should be explicitly stated.
`The dream of a cigarettes – free world is just
`that – a dream. Nicotine’s effects, observed in
`nicotine consumers, include correcting problems
`with the ability to remember, pay attention, and
`concentrate, as well as improving symptoms of
`mood disorders. Keeping such disabilities at bay
`right now can be much stronger motivation to con-
`tinue smoke cigarettes than any threats of diseases
`that may strike years and years in the future. For
`smokers unwilling to quit, nicotine’s effects can be
`harnessed and the harmful effects of the delivery
`mechanism can be attenuated by providing nico-
`tine from less dangerous sources than inhaling to-
`bacco smoke. For these reasons electronic ciga-
`rette could become a promising tool – if studied
`more extensively and deeply – in the fight against
`tobacco-related morbidity and mortality.
`
`Acknowledgements: Riccardo Polosa is full Professor
`of Internal Medicine and he is supported by the University
`of Catania, Italy.
`
`Conflict of Interest: None of the authors have any
`competing interests to declare, with the exception of RP. RP
`has received lecture fees from Pfizer and GSK, a research grant
`from Pfizer, and he served as a consultant for Pfizer, Global
`Health Alliance for treatment of tobacco dependence, and
`Arbi Group Srl.
`
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