Tobacco harm reduction

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Tobacco harm reduction (THR) is a public health strategy to lower the health risks to individuals and wider society associated with using tobacco products. It is an example of the concept of harm reduction, a strategy for dealing with the abuse of other drugs. Tobacco smoking is widely acknowledged as a leading cause of illness and death,[1] and preventing smoking is vital to public health.

In the developed world, a reduction in the prevalence of smoking has been primarily achieved through reducing the uptake of smoking among younger people rather than improving the rates of quitting in established smokers. It is, however, this latter group who will generate the greatest source of population burden of morbidity and premature mortality caused by smoking in the next twenty years.[2][3]

Nicotine itself, however, is not very harmful, as inferred from the long history of use for nicotine replacement therapy products.[4] Nicotine increases heart rate and blood pressure and has a range of local irritant effects but is not carcingogenic (cancer causing).[5] Indeed, none of the three main causes of mortality from smoking, lung cancer, COPD and cardiovascular disease, is caused primarily by nicotine. The main hazardous component is the smoke which results from the combustion of tobacco, so if nicotine could be effectively and acceptably delivered without smoke, it is likely that most if not all the harm of smoking could be avoided. THR measures have been focused on reducing or eliminating the use of combustible tobacco by switching to other nicotine products, including:

  1. Cutting down (either long-term or before quitting smoking)
  2. Temporary abstinence
  3. Switching to non-tobacco nicotine containing products, such as pharmaceutical nicotine replacement therapies or currently (generally) unlicensed products such as electronic cigarettes
  4. Switching to smokeless tobacco products such as Swedish snus
  5. Switching to non-combustible organic or additive-free tobacco products

It is widely acknowledged that discontinuation of all tobacco products confers the greatest lowering of risk. However, approved smoking cessation methods have a 90% failure rate, when used as directed.[1] In addition, there is a considerable population of smokers who are unable or unwilling to achieve abstinence.[6] Harm reduction is likely of substantial benefit to these smokers and public health.[1][4] Providing reduced-harm alternatives to smokers is likely to result in lower total population risk than pursuing abstinence-only policies.[7]

The strategy is controversial: proponents of tobacco harm reduction assert that lessening the health risk for the individual user is worthwhile and manifests over the population in fewer tobacco-related illnesses and deaths.[6][8] Opponents have argued that some aspects of harm reduction interfere with cessation and abstinence and might increase initiation.[9][10] However, surveys carried from 2013 to 2015 in the UK[11] and France [12] suggest that on the contrary, the availability of safer alternatives to smoking is associated with decreased smoking prevalence and increased smoking cessation.

History[edit]

The concept of tobacco harm reduction was established in 1976 when Professor Michael Russell wrote: "People smoke for nicotine but they die from the tar"[13] and suggested that the ratio of tar to nicotine could be the key to safer smoking.[4][6] Since then, the harm from smoking has been well-established as being caused almost exclusively by toxins released through the combustion of tobacco.[1] In contrast, non-combustible tobacco products as well as pure nicotine products are considerably less harmful, although they still have the potential for addiction.[4]

Debates on tobacco harm reduction tend to be geographically defined arguments, because of the varying legal, moral, and historical status of tobacco, and the different types of tobacco products and use in different cultures around the world. For instance, cigarette smoking is the dominant form in the United States, while use of cigars, pipes, and smokeless tobacco is limited to a much smaller population. Anti-smoking advocacy efforts and widespread popularization of the negative health effects of smoking over the last few decades have led to restrictions in the sale and use of tobacco products. Despite this, tobacco in all its forms has remained a legal product in most societies. A notable exception is the European Union, where the most dangerous products (cigarettes) are available but smokeless tobacco products, which are far less hazardous, are banned.[14] The exception is Sweden, where there is a long tradition of smokeless tobacco (snus) use among men.

In October 2008 the American Association of Public Health Physicians (AAPHP) became the first medical organization in the U.S. to officially endorse tobacco harm reduction as a viable strategy to reduce the death toll related to cigarette smoking.[15][16][17] Joel Nitzkin, MD[18] wrote: "So if we can figure that the nicotine in the e-cigarettes is basically a generic version of the same nicotine that is in prescription products, we have every reason to believe that the hazard posed by e-cigarettes would be much lower than one percent, probably lower than one tenth of one percent of the hazard posed by regular cigarettes."[19]

"Safer cigarettes"[edit]

Light Cigarettes

Cigarette manufacturers have attempted to design safer cigarettes for almost 50 years, but results have been marginal at best.[20] Filters were introduced in the early 1950s, and manufacturers were selling low-yield cigarettes by the late 1960s.[20] Initially it was thought that these innovations were harm reducing.[21] For example, in 1976 investigators at the American Cancer Society published research concluding that light cigarettes were safer.[22] The study authors wrote that "total death rates, death rates from coronary heart disease, and death rates from lung cancer were somewhat lower for those who smoked 'low' tar-nicotine cigarettes than for those who smoked 'high' tar-nicotine cigarettes." However, scientific evidence suggests that switching from regular to light or low-tar cigarettes does not reduce the health risks of smoking or lower the smoker's exposure to the nicotine, tar, and carcinogens present in cigarette smoke.[23] Indeed, part of the World Health Organization’s Framework Convention on Tobacco Control’s Article 11 and its accompanying guidelines recommend that misleading terms, including ‘light’ and ‘mild’, should be removed from tobacco product advertising, packaging, and labeling,.[24][25]

Smokeless tobacco[edit]

It has been established that use of Swedish and American smokeless tobacco confers only 0.1% to 10% of the risks of smoking,[6] though smokeless products in India and elsewhere in Asia contain higher levels of contaminants and thus confer greater risks.[8] Two respected medical groups believe that smokeless tobacco may play a role in reducing smoking-attributable deaths. In 2007, Britain's Royal College of Physicians concluded "...that smokers smoke predominantly for nicotine, that nicotine itself is not especially hazardous, and that if nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved." [26]

In the United States, a study based on National Health Interview Survey data found that 73% of smokers who switched to smokeless tobacco as part of their latest quit attempt were successful in quitting smoking.[27] In the same study, smokers who used pharmaceutical nicotine products in their most recent quit attempt had success rates between 0 and 35%.[27]

Snus[edit]

Scandinavian snus is a moist form of smokeless tobacco which is usually placed under the upper lip, and is not smoked or swallowed. A 2014 report commissioned by Public Health England on another avenue for tobacco harm reduction, electronic cigarettes, said snus "has a risk profile that includes possible increases in risk of oesophageal and pancreatic cancer, and of fatal (but not non-fatal) myocardial infarction, but not COPD or lung cancer." The report examined the case of snus as "a unique natural experiment in the impact of a socially accepted, non-medical, affordable and easily accessible reduced harm product on the prevalence of tobacco smoking". They concluded that "Although controversial, the Swedish natural experiment demonstrates that despite dual use and primary uptake of the reduced-harm product by young people, availability of reduced-harm alternatives for tobacco smokers can have a beneficial effect. While snus is not likely to become a legal or indeed politically viable option in the UK, this data proves the concept that harm reduction strategies can contribute to significant reductions in smoking prevalence."[28]

Based on the mounting evidence that the health risks of Swedish snus are far lower than those of combustible tobacco products, in August 2014, Swedish Match (a manufacturer) filed a Modified Risk Tobacco Product (MRTP) application with the FDA Center for Tobacco Products (CTP). The MRTP application seeks to modify the warning labels on smokeless tobacco products such that they reflect the evidence of reduced-harm compared to smoking. Among the proposed labeling changes, the MRTP application requests replacing the current warning, "This product is not a safe alternative to cigarettes," with this text: "No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes."[29]

Electronic cigarettes[edit]

E-cigarettes are battery-powered devices that provide nicotine for inhalation in a vapour generated by heating a solution of water, nicotine propylene glycol or vegetable glycerin and typically some flavouring. They were first developed in China in 2003, and first introduced to Europe and the US around 2006.[30]

There are many brands and models of e-cigarettes available today but they can be broadly grouped into three categories. First generation e-cigarettes are similar in appearance to a conventional cigarette and are typically designed to be for single use. Second generation e-cigarettes are around the size of a large fountain pen, have a battery linked to a permenant vapouriser and a refillable tank for the nicotine solution. Third generation e-cigarettes tend to be larger, with a more powerful battery and two heating elements which allow users to carry the power.[26] Nicotine delivery has typically increased with successive generations of e-cigarette,[31] and it has been suggested that repeated use of second and third generation devices can result in sustained venous blood levels of nicotine which are comparable with those expected in smokers.[32]

Electronic cigarettes are a promising harm reduction technology because they deliver nicotine without the dangerous chemicals in tobacco smoke, while remaining attractive to smokers.[4] While the eventual regulatory status of e-cigarettes in many countries remains uncertain,[4] public health advocates view electronic cigarette as having a valid place within tobacco harm reduction strategy.[33] In a first step towards the regulation of e-cigarettes, the MHRA granted Marketing Authorisations (licences) for the medicinal products e-Voke 10 mg and 15 mg Electronic Inhaler (PL 40317/0001-2) on 16 November 2015.[34] Public health researchers in the UK estimated that 6,000 premature smoking-related deaths per year would be prevented for every million smokers who switched to e-cigarettes.[33] Since currently approved smoking cessation methods have a 90% failure rate, the use of e-cigarettes as a prominent THR modality is likely to substantially reduce tobacco-related illness in the United States, with the potential to save 4.8 million lives over the next 20 years.[1]

A survey of UK adults found that over two thirds of ex-smokers and over one third of current smokers report that one of the main reasons they use e-cigarettes is to help them stop smoking completely.[35]

Research into the safety and efficacy of e-cigarettes for smoking cessation, published up until January 2016, is limited, but suggests a potential increase in long term smoking cessation using e-cigarettes containing nicotine compared to those without, with no increased health risk compared to smokers with medium term use (two years or less).[36]

As with any new product, long term or rare adverse effects will not become clear until e-cigarettes have been in widespread use for decades. However, in an effort to decrease tobacco related death and disease, e-cigarettes appear to have a potential to be part of the strategy.[37]

Regulation of e-cigarettes varies around the world. The Institute for Global Tobacco Control (IGTC) has identified 68 countries that have laws regulating e-cigarettes, as at November 2016.[38] Types of regulation include complete prohibition on the sale and marketing of e-cigarettes, prohibition on their use in enclosed public places, minimum age for purchase, an allowance for e-cigarettes to be sold under general consumer product regulations and most recently, in the UK, e-cigarettes may be brought to market as either medicines or consumer products (with those seeking medicines approval undergoing the standard medicines licensing process). The World Health Organization acknowledge that e-cigarettes may play a role in harm reduction strategies, but should be regulated to minimize any potential risks. However, the vast differences in regulatory approaches evident around the world highlights the challenge of developing a global regulatory approach.

Propellant-based nicotine delivery[edit]

An alternative nicotine delivery platform based on existing asthma inhaler technology has been developed by a UK-based healthcare company, Kind Consumer Limited. The technology is under license to Nicoventures Limited a subsidiary of British American Tobacco who are responsible for the launch and commercialization of the technology as an approved nicotine replacement therapy product. The MHRA granted Marketing Authorizations (licenses) for the medicinal products Voke/Nicotine 0.45 mg Inhaler (PL 39589/0001-2) on 11 September 2014, with a variation to the license to support full commercialization granted on 23 February 2015.

Nicotine pyruvate technology[edit]

Philip Morris International bought the rights to a nicotine pyruvate technology developed by Jed Rose at Duke University.[39] The technology is based around the chemical reaction between nicotine acid and a base which produces a nicotine pyruvate vapour for inhalation.[40] It has undergone preliminary clinical evaluation which has shown delivery of nicotine to the lungs.[41]

Public perceptions[edit]

Smokers remain confused about tobacco harm reduction. In a 2004 survey, about 80-100% of participants incorrectly perceived low-yield cigarettes as harm-reducing, while 75-80% mistakenly believed that switching to smokeless tobacco conferred no risk reduction.[42]

Similar confusion exists about electronic cigarettes. In the UK, research commissioned by the anti-smoking charity Action on Smoking and Health found that in 2016, more than three times as many people think e-cigarettes are as harmful or more harmful than smoking than in 2013 (25% vs 7%), the highest proportion since the survey began.[35] They expressed concern that the proportion of adult smokers who thought that e-cigarettes were more or equally harmful than cigarettes was highest in those who had never tried e-cigarettes, and these perceived potential harms was the main reason why they had not tried them.[35]

In 2015 a report commissioned by Public Health England noted, as well as the UK figures above, that in the US belief among responders to a survey that vaping was safer than smoking cigarettes fell from 82% in 2010 to 51% in 2014.[43] The report blamed "misinterpreted research findings", attracting negative media coverage, for the growth in the "inaccurate" belief that e-cigarettes were less harmful than smoking, and concluded that "There is a need to publicise the current best estimate that using EC is around 95% safer than smoking".[44]

In an article published by the Wall Street Journal in 2016 entitled "Are E-Cigarettes a Healthy Way to Quit Smoking?", Dr. Jed E. Rose co-inventor of the nicotine patch said, "Having worked my entire career to develop effective smoking-cessation treatments, I have realized that current approaches are ineffective for the vast majority of smokers. Alternative approaches are urgently needed. The World Health Organization predicts[45] a billion deaths will be attributable to smoking during the 21st century. Electronic cigarettes have an unparalleled potential to reduce the public-health impact of smoking, by allowing smokers to replace the habit and nicotine of smoking without the toxic effects of combustion."[46]

Concerns around tobacco harm reduction strategies[edit]

Whilst tobacco harm reduction approaches have the potential to reduce risks to the current adult smoking population, there are hypothesised potential hazards to wider public health. Smoking has become less acceptable over recent years in a number of countries, a result of a number of he Framework Convention on Tobacco Control (FCTC) guidelines to reduce smoking prevalence. The renormalisation of smoking is a concern if e-cigarette use appears to become more appealing, for example through their use in locations where conventional cigarettes are prohibited, advertising and increased e-cigarette use by parents, siblings, peers, celebrities or other influential groups.[47][48]

Concerns have also been raised that non-tobacco nicotine use may results in uptake of tobacco smoking that would not otherwise have occurred. This ‘gateway theory’ has been largely applied to the use of e-cigarettes by non-smokers and particularly children.[49] There is no reported evidence, however, that NRT use among young people has ever acted as a gateway to smoking, or that e-cigarette use has resulted in any appreciable increase initiation of smoking among children or adults. The Royal College of Physicians suggest that any association between e-cigarette and conventional cigarette use is likely due to common liability to use these products and the use of e-cigarettes to reduce smoking.[26]

Dual use of tobacco products and non-tobacco nicotine by continuing smokers is another aspect which has raised concern. It is suggested that dual use could inadvertently sustain smoking by making it easier for smokers to temporarily abstain from tobacco use, or encourage smokers to move towards dual use rather than complete cessation in the mistaken belief that this offers significant health gains. Dual use of tobacco and NRT is licensed by the Medicines and Healthcare products Regulatory Authority (MHRA) as a tobacco harm reduction strategy which actually increases the chance of quitting.[50] The Royal College of Physicians reviewed evidence around dual use and smoking cessation and reported that findings were suggestive that e-cigarettes had the potential to offer the same cessation gains,[26] although further research would be helpful to more clearly delineate such an effect.

See also[edit]

References[edit]

  1. ^ a b c d e Nitzkin, J (June 2014). "The Case in Favor of E-Cigarettes for Tobacco Harm Reduction". Int J Environ Res Public Health. 11 (6): 6459–71. doi:10.3390/ijerph110606459. PMC 4078589Freely accessible. PMID 25003176. A carefully structured Tobacco Harm Reduction (THR) initiative, with e-cigarettes as a prominent THR modality, added to current tobacco control programming, is the most feasible policy option likely to substantially reduce tobacco-attributable illness and death in the United States over the next 20 years. 
  2. ^ "IARC Monographs- Tobacco smoke and involuntary smoking". monographs.iarc.fr. International Agency for Research on Cancer. Retrieved 18 April 2017. 
  3. ^ Jha, P; Peto, R (2 January 2014). "Global effects of smoking, of quitting, and of taxing tobacco.". The New England Journal of Medicine. 370 (1): 60–8. doi:10.1056/nejmra1308383. PMID 24382066. 
  4. ^ a b c d e f Fagerström, KO, Bridgman, K (March 2014). "Tobacco harm reduction: The need for new products that can compete with cigarettes". Addictive Behaviors. 39 (3): 507–511. doi:10.1016/j.addbeh.2013.11.002. PMID 24290207. The need for more appealing, licensed nicotine products capable of competing with cigarettes sensorially, pharmacologically and behaviourally is considered by many to be the way forward. 
  5. ^ "IARC Monographs- Classifications". monographs.iarc.fr. International Agency for Research on Cancer. Retrieved 18 April 2017. 
  6. ^ a b c d Rodu, Brad; Godshall, William T. (2006). "Tobacco harm reduction: An alternative cessation strategy for inveterate smokers". Harm Reduction Journal. 3: 37. doi:10.1186/1477-7517-3-37. PMC 1779270Freely accessible. PMID 17184539. 
  7. ^ Phillips, CV (November 2009). "Debunking the claim that abstinence is usually healthier for smokers than switching to a low-risk alternative, and other observations about anti-tobacco-harm-reduction arguments". Harm Reduct. J. 6: 29. doi:10.1186/1477-7517-6-29. PMC 2776004Freely accessible. PMID 19887003. Hiding THR from smokers, waiting for them to decide to quit entirely or waiting for a new anti-smoking magic bullet, causes the deaths of more smokers every month than a lifetime using low-risk nicotine products ever could. 
  8. ^ a b "Harm reduction in nicotine addiction: Helping people who can't quit" (PDF). Tobacco Advisory Group of the Royal College of Physicians. October 2007. Retrieved 21 April 2012. 
  9. ^ Sumner, W (2005). "Permissive nicotine regulation as a complement to traditional tobacco control". BMC Public Health. 5: 18. doi:10.1186/1471-2458-5-18. 
  10. ^ Tomar, SL; Fox, BJ; Severson, HH (2009). "Is smokeless tobacco use an appropriate public health strategy for reducing societal harm from cigarette smoking?". Int J Environ Res Public Health. 6: 10–24. doi:10.3390/ijerph6010010. 
  11. ^ Action on Smoking and Health, May 2016, Use of electronic cigarettes (vapourisers) among adults in Great Britain [1]
  12. ^ Résultats de l'enquête cigarette électronique ETINCEL - OFDT, 2014
  13. ^ Russell, MA (June 1976). "Low-tar medium-nicotine cigarettes: a new approach to safer smoking". Br Med J. 1 (6023): 1430–3. doi:10.1136/bmj.1.6023.1430. PMC 1640397Freely accessible. PMID 953530. 
  14. ^ Bates, C; Fagerstrom, K; Jarvis, MJ; Kunze, M; McNeill, A; Ramstrom, L (2003). "European Union policy on smokeless tobacco: a statement in favour of evidence based regulation for public health". Tob Control. 12: 360–367. doi:10.1136/tc.12.4.360. PMC 1747769Freely accessible. PMID 14660767. 
  15. ^ Update on the Scientific Status of Tobacco Harm Reduction, 2008-2010. Prepared for the American Association of Public Health Physicians. Brad Rodu, DDS and Joel L Nitzkin, MD. June 28, 2010.
  16. ^ Principles to Guide AAPHP Tobacco Policy. American Association of Public Health Physicians.
  17. ^ Rodu, B. (2011). "The scientific foundation for tobacco harm reduction, 2006-2011". Harm Reduction Journal. 8: 19–99. doi:10.1186/1477-7517-8-19. PMC 3161854Freely accessible. PMID 21801389. 
  18. ^ Joel L Nitzkin. LinkedIn.
  19. ^ "Electronic Cigarette Interview with Dr Joel Nitzkin.". The Smokers ANgel. Retrieved 25 November 2013. 
  20. ^ a b Rigotti, NA; Tindle, HA (2004). "The fallacy of light cigarettes". BMJ. 328: 278–279. doi:10.1136/bmj.328.7440.E278. PMC 2901853Freely accessible. PMID 15016715. 
  21. ^ Russell, MAH (1974). "Realistic goals for smoking and health: a case for safer smoking". Lancet. 1: 254–258. doi:10.1016/s0140-6736(74)92558-6. 
  22. ^ Hammond, EC; Garfinkel, L; Seidman, H; Lew, EA (1976). "Tar and nicotine content of cigarette smoke in relation to death rates". Environ Res. 12: 263–274. doi:10.1016/0013-9351(76)90036-0. PMID 1001298. 
  23. ^ Benowitz, NL; Jacob P, 3rd; Bernert, JT; Wilson, M; Wang, L; Allen, F; Dempsey, D (June 2005). "Carcinogen exposure during short-term switching from regular to "light" cigarettes.". Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 14 (6): 1376–83. doi:10.1158/1055-9965.epi-04-0667. PMID 15941944. 
  24. ^ "WHO Framework Convention on Tobacco Control". World Health Organization. World Health Organization. 
  25. ^ "WHO Guidelines for implementation of the WHO FCTC". www.who.int. World Helath Organization. 
  26. ^ a b c d "Nicotine without smoke: Tobacco harm reduction". RCP London. Royal College of Physicians. 28 April 2016. 
  27. ^ a b Rodu, B; Phillips, CV (May 2008). "Switching to smokeless tobacco as a smoking cessation method: evidence from the 2000 National Health Interview Survey". Harm Reduct J. 5: 18. doi:10.1186/1477-7517-5-18. Switching to ST compares very favorably with pharmaceutical nicotine as a quit-smoking aid among American men, despite the fact that few smokers know that the switch provides almost all of the health benefits of complete tobacco abstinence. 
  28. ^ Britton, John; Bogdanovica, Ilze (15 May 2014). "Electronic cigarettes – A report commissioned by Public Health England" (PDF). Public Health England. pp. 11–12. 
  29. ^ "Swedish Match North America MRTP Applications". 27 August 2014. pp. 100,000+. Retrieved 24 October 2014. 
  30. ^ Wlesenthal, Kelly (2013). "Electronic Cigarette History". Retrieved 25 November 2013. 
  31. ^ Talih, S; Balhas, Z; Eissenberg, T; Salman, R; Karaoghlanian, N; El Hellani, A; Baalbaki, R; Saliba, N; Shihadeh, A (February 2015). "Effects of user puff topography, device voltage, and liquid nicotine concentration on electronic cigarette nicotine yield: measurements and model predictions.". Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. 17 (2): 150–7. doi:10.1093/ntr/ntu174. PMC 4837998Freely accessible. PMID 25187061. 
  32. ^ Ramôa, CP; Hiler, MM; Spindle, TR; Lopez, AA; Karaoghlanian, N; Lipato, T; Breland, AB; Shihadeh, A; Eissenberg, T (April 2016). "Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report.". Tobacco control. 25 (e1): e6–9. doi:10.1136/tobaccocontrol-2015-052447. PMC 4888876Freely accessible. PMID 26324250. 
  33. ^ a b West, R, Brown J (September 2014). "Electronic cigarettes: fact and faction". British Journal of General Practice. 64 (626): 442–3. doi:10.3399/bjgp14X681253. PMC 4141591Freely accessible. PMID 25179048. It is important that interpretation of the evidence and communication with policy makers and the public is not distorted by a priori judgements. 
  34. ^ (PDF). Medicines and Healthcare Products Regulatory Association http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con616843.pdf.  Missing or empty |title= (help)
  35. ^ a b c "Use of electronic cigarettes (vapourisers) among adults in Great Britain | Action on Smoking and Health". ash.org.uk. Action on Smoking and Health. 
  36. ^ Hartmann-Boyce, Jamie; McRobbie, Hayden; Bullen, Chris; Begh, Rachna; Stead, Lindsay F; Hajek, Peter (13 September 2016). "Electronic cigarettes for smoking cessation". Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd. 9: CD010216. doi:10.1002/14651858.cd010216.pub3. PMID 27622384. 
  37. ^ M., Z.; Siegel, M (February 2011). "Electronic cigarettes as a harm reduction strategy for tobacco control: a step forward or a repeat of past mistakes?". Journal of public health policy. 32 (1): 16–31. doi:10.1057/jphp.2010.41. PMID 21150942. 
  38. ^ "Country Laws Regulating E-cigarettes | Global Tobacco Control - Learning from the Experts". globaltobaccocontrol.org. Institute for Global Tobacco Control. 
  39. ^ "News Release May 26, 2011". Pmi.com. 
  40. ^ "New smoking cessation therapy proves promising". e! Science News. 2010-02-27. 
  41. ^ Rose, J. E.; Turner, J. E.; Murugesan, T.; Behm, F. D. R. M.; Laugesen, M. (2010). "Pulmonary delivery of nicotine pyruvate: Sensory and pharmacokinetic characteristics" (PDF). Experimental and Clinical Psychopharmacology. 18 (5): 385–394. doi:10.1037/a0020834. PMID 20939642. 
  42. ^ Haddock, CK; Lando, H; Klesges, RC; Peterson, AL; Scarinci, IC (2004). "Modified tobacco use and lifestyle change in risk-reducing beliefs about smoking". Am J Prev Med. 27: 35–41. doi:10.1016/j.amepre.2004.03.010. 
  43. ^ McNeill, A, SC (2015). "E - cigarettes: an evidence update A report commissioned by Public Health England" (PDF). www.gov.uk. UK: Public Health England. p. 79. Retrieved 20 August 2015. 
  44. ^ McNeill, A, SC (2015). "E - cigarettes: an evidence update A report commissioned by Public Health England" (PDF). www.gov.uk. UK: Public Health England. Retrieved 20 August 2015. , pages 6, 11, 78-80
  45. ^ "Who Report On The Global Tobacco Epidemic, 2008" (PDF). US. Retrieved 21 April 2016. 
  46. ^ "Are E-Cigarettes a Healthy Way to Quit Smoking?". www.wsj.com. US: Wall Street Journal. Retrieved 21 April 2016. 
  47. ^ Fairchild, A.L.; Bayer, R.; Colgrove, J. [ecig.co/wp-content/uploads/2014/06/nejmp-e-cig-article.pdf "The renormalization of smoking? E-cigarettes and the tobacco "endgame""] Check |url= value (help) (PDF). New England Journal of Medicine. 
  48. ^ Voigt, K (October 2015). "Smoking Norms and the Regulation of E-Cigarettes.". American Journal of Public Health. 105 (10): 1967–72. doi:10.2105/ajph.2015.302764. PMC 4566542Freely accessible. PMID 26270285. 
  49. ^ Bell, K; Keane, H (October 2014). "All gates lead to smoking: the 'gateway theory', e-cigarettes and the remaking of nicotine.". Social science & medicine (1982). 119: 45–52. doi:10.1016/j.socscimed.2014.08.016. PMID 25150650. 
  50. ^ "The use of nicotine replacement theory to reduce harm in smokers" (PDF). MHRA Public Assessment Report. MHRA.