E-Cigarettes: The good, the bad and the unknown

An electronic cigarette (e-cigarette) is a battery-powered device containing a liquid substance that is vaporized and then inhaled in a manner analogous to a traditional cigarette. The ‘e-liquid’ may or may not contain nicotine. Importantly, nicotine-containing e-cigarettes are not authorized for sale in Canada, while those that do not contain nicotine are authorized for sale, provided that no health claims are made related to their use.¹

According to Health Canada regulation, nicotine-containing e-cigarettes are within the scope of the Food and Drugs Act and, as such, require market authorization based upon clinical evidence of safety, quality and efficacy, prior to being imported, advertised or sold in Canada. No nicotine-containing e-cigarette has been granted such authorization in Canada, yet they are readily available nationwide, which has contributed to the controversy and debate surrounding their use.¹

On the plus side: harm reduction

Despite overwhelming evidence of harm and financial burden, the majority of smokers find it extremely difficult or impossible to quit. From a harm reduction perspective, e-cigarettes reduce exposure to the innumerable carcinogens and toxins found in cigarette smoke.² An e-cigarette can be a replacement for a conventional cigarette in satisfying the chemical and behavioural aspects of cigarette smoking.

Moreover, in a number of survey, the potential advantages of using e-cigarettes vs. conventional cigarettes included the following:³

• They may make it easier for you to cut down the number of cigarettes smoked, and help people quit altogether
• They may not be as bad for people’s health
• They taste better than conventional cigarettes, and there is no tobacco smoke associated with their use
• They can be used in places where smoking regular cigarettes is banned
• They may provide a viable aid for people who have attempted previous cessation endeavours to quit altogether

With respect to harm reduction, Nutt and colleagues investigated the relative importance of different types of harm related to the use of nicotine-containing products, using a multi-criteria decision analysis model. The authors concluded that cigarettes are the nicotine product causing by far the most harm to users and others in the world today. Attempts to switch to non-combusted sources of nicotine should be encouraged, as the harms from these products are much lower.⁴

On the negative side: unproven as safe or effective and may renormalize smoking

The evidence supporting the safety and efficacy of e-cigarettes is limited. A recent systematic review of the literature identified only two completed randomized controlled trials (RCTs) of e-cigarettes, whereas the remainder of evidence included in the review came from cohort studies that were rated as having a high risk of bias.⁵ Based upon the two RCTs, participants who used nicotine-containing e-cigarettes were more likely to have abstained from smoking, compared with participants who used non-nicotine containing e-cigarettes (RR 2.29, 95% CI 1.05–4.96). However, the six-month abstinence rates were 4% for non-nicotine containing e-cigarettes and 9% for nicotine-containing e-cigarettes; the grade of evidence was considered to be low.

Further, given that Health Canada does not regulate e-cigarettes, they are not held to the same stringent effectiveness and safety checks as those required for drugs and nicotine replacement therapies. It is concerning that most people who use e-cigarettes also continue to smoke conventional cigarettes, which brings into question the efficacy of e-cigarettes for quitting.⁶ In addition, adverse effects after smoking a single e-cigarette, such as cough, sore throat, eye irritation and increases in airway resistance and heart rate, have been reported in the literature, suggesting that there is potential for e-cigarettes to harm the respiratory system.⁷ In an animal model, e-cigarette exposure was associated with significantly impaired pulmonary bacterial clearance of Streptococcus pneumonia and enhanced virus-induced illness and mortality with influenza A.⁸ Further, e-cigarettes are a source of second-hand exposure to nicotine. Therefore, using an e-cigarette in indoor environments may involuntarily expose nonusers to nicotine.⁹

Another concern with e-cigarettes is that their use may undo some of the ‘denormalization’ of smoking achieved by smoke-free legislation and other measures, and create new smoking role models for children.¹⁰ Some are concerned over how to manage the challenges that these products present to current norms of clinical practice. One such concern is whether e-cigarette use should be permitted in inpatient settings or on hospital grounds. An additional issue with the use of nicotine containing e-cigarettes relates to the observation that nicotine may be a ‘gateway drug.’ According to the gateway hypothesis, there is a well-defined developmental sequence of drug use that begins with legal drugs (e.g. nicotine and alcohol), which leads to illicit drug use (e.g. marijuana and cocaine).¹¹

Thus, with the uptake of e-cigarettes in the younger population, there is a possibility that this may create a new generation addicted to nicotine, which may be the precursor to the use of other drugs as well. Of concern are the results of a US-based survey conducted in 2014 that found that for the first time, e-cigarette use surpassed that of traditional cigarettes and other tobacco products in high school students.¹² Moreover, e-cigarette ad campaigns have been described as disproportionately appealing to youth, based on celebrity endorsements, trendy imagery and fruit, candy and alcohol flavours. Further, many are discomfited by the fact that the major tobacco companies responsible for the global smoking epidemic are all developing or acquiring e-cigarettes and other nicotine devices.¹⁰

The unknown

In addition to the lack of long-term studies on the safety and efficacy of e-cigarettes, uncertainty about their chemical composition remains. Frequently, the chemical composition of the e-liquid contained within an e-cigarette is not provided on the product labelling and when the information is available, it tends to be incomplete.¹⁰ Components may be listed simply as “additives”. For nicotine containing e-cigarettes, the labelled content may be nonspecific, with nicotine being listed as low, medium or high concentration, so comparisons with conventional cigarettes (milligrams/cigarette) are difficult.

As well, analysis of the contents of e-cigarettes has identified some potentially toxic components, including trace levels of tobacco-specific nitrosamines (cancer-causing compounds commonly found in traditional cigarettes), diethylene glycol (a component of antifreeze and brake fluid), and particles of silver, iron, aluminum and silicate and nanoparticles of tin, chromium and nickel in concentrations higher than or equal to those found in conventional cigarette smoke.¹³ In addition, traces of tadalafil (a PDE5 inhibitor) and rimonabant (an anti-obesity drug withdrawn from the European market due to safety concerns), have been detected in some brands.¹⁴ Further, analysis of the aerosol created when “vaping” e-cigarettes has found that formaldehyde-releasing agents are formed during the process, the effects of which are unknown but may pose risk, given that formaldehyde is a carcinogen.¹⁵

Summary

Clinicians should take every opportunity to strongly encourage their patients who smoke cigarettes to stop, and should assist in their quit attempts by using the evidence-based cessation treatments and behavioural support. Given the lack of evidence of safety, efficacy and quality standards of e-cigarettes, further clinical trials and subsequent approval for market authorization in Canada are needed in order to establish their role in smoking cessation. Until then, healthcare practitioners should use their professional judgement to assist patients with navigating the continuum of risk.¹⁶

References

1. Health Canada. Notice – To All Persons Interested in Importing, Advertising or Selling Electronic Smoking Products in Canada. Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/pol/notice_avis_e-cig-eng.php. Accessed April 18, 2016.
2. Alwood B. Electronic cigarettes: The potential benefits outweigh the risks. S Afr Med J. 2013;103(11):832–833.
3. McNeill A, Brose LS, Calder R, et al. E-cigarettes: An Evidence Update. London, UK: Public Health England; 2015. Available at: https://www.gov.uk/government/publications/e-cigarettes-an-evidence-update. Accessed April 18, 2016.
4. Nutt DJ, Phillips LD, Balfour D, et al. estimating the harms of nicotine-containing products using the MCDA approach. Eur Addict Res. 2014;20:218–225.
5. McRobbie H, Bullen C, Hartmann-Boyce J, et al. Electronic cigarettes for smoking cessation and reduction. Cochrane Database Syst Rev. 2014;12:CD010216.
6. Regan AK, Promoff G, Dube SR, et al. Electronic nicotine delivery systems: adult use and awareness of the ‘e-cigarette’ in the USA. Tob Control. 2013;22(1):19–23.
7. Gennimata S et al. Acute effect of e-cigarette on pulmonary function in healthy subjects and smokers. European Respiratory Society Annual Congress; 2012.
8. Sussan TE, Gajghate S, Thimmulappa RK, et al. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and antiviral defenses in a mouse model. PLoS One. 2015;10(2):e0116861.
9. Czogala J, Goniewicz ML, Fidelus B, et al. Second-hand exposure to vapors from electronic cigarettes. Nicotine Tob Res. 2014;16(6):655–662.
10. Britton J. Electronic cigarettes. Thorax. 2013; 68(10): 904–905.
11. Kandel ER, Kandel DB. A molecular basis for nicotine as a gateway drug. N Engl J Med. 2014;371:932–943.
12. University of Michigan website. E-cigarettes surpass tobacco cigarettes among teens. Available at:
13. http://tinyurl.com/jmomk64. Accessed January 22, 2016.
14. Adkins BW. Electronic cigarette smokers: be wary. W V Med J. 2014;110(1):8.
15. Hadwiger ME, Trehy ML, Ye W, et al. Identification of aminotadalafil and rimonabant in electronic cigarette products using high pressure liquid chromatography with diode array and tandem mass spectrometric detection. J Chromatog A. 2010;1217(48):7547–7555.
16. Jensen RP, Luo W, Pankow JF, et al. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med.2015;372(4):392–394.
17. Abrams DB. Promise and peril of e-cigarettes: can disruptive technology make cigarettes obsolete? JAMA. 2014;311:135–136.