Opinion-No: Emily Stone, MBBS, MMed
There is little doubt that lung cancer patients and the people around them who smoke need to stop. Smoking cessation can improve survival,1 surgical outcomes,2-4 and response to anticancer therapies5 and can reduce the risk of recurrence.6 However, many physicians feel poorly trained and unsure about providing smoking cessation advice; even if they advise their patients to quit, they often fail to follow through with specific measures.7-9 There are many compelling arguments to include e-cigarettes in smoking cessation. They may give smokers autonomy. They may address the urgency of smoking cessation in lung cancer patients. They may be less dangerous than tobacco cigarettes although the data are not entirely clear.10 If we could sell them under tight regulation, we could minimize the risks.11 But these arguments carry inherent flaws with a profusion of contradictory evidence. We have plenty of access to effective, alternative forms of nicotine with a longer safety track record supported by evidence.12 With good advice, smokers can exercise autonomy over their choice of nicotine replacement from the more established products. Regulatory frameworks may be harder to put in place than we think.
Although e-cigarettes have attracted significant support as smoking cessation tools from at least 1 major public health entity,13 2 recent systematic reviews cast doubt upon such claims. The first reviewed 38 studies and found that smokers who used e-cigarettes had lower rates of quitting than those who did not.14 The second reviewed 12 studies, including 3 randomized trials and found only very limited evidence that e-cigarettes aided smoking cessation.15 E-cigarettes may even have the potential to increase smoking rates in teenagers, with a recent study showing that e-cigarette use was associated with a 4-fold increase in tobacco cigarette smoking.16 The marketing of e-cigarettes may undermine the smoking cessation message; advertisements recommend that smokers “switch,” rather than “quit” and use familiar strategies to glamorize the smoking of e-cigarettes.17
Safety data on e-cigarettes are immature. Some studies suggest that e-cigarettes are better: in vitro data have shown reduced cytotoxicity18; exposure chamber data indicate lower levels of secondhand exposure to toxic combustion products.19 However, other reports demonstrate that in vitro exposure to e-liquid results in reduced cell viability20 and increased inflammatory responses.21 Studies have also reported the presence of toxic aldehydes in e-liquids (particularly from flavorings)22 and the potential for harm from passive exposure to e-cigarette vapor.23 Other safety issues, such as leaks, fires, explosions,24,25 and danger to children, 26,27 add to these concerns.
Does the urgency for smoking cessation in lung cancer patients make e-cigarettes a more necessary option? No—there are plenty of guidelines to smoking cessation, replete with information on nicotine replacement therapy, other pharmacotherapies such as varenicline and bupropion, appropriate behavioral strategies, and advice on combining approaches.28-31 In many cases, these strategies are underused32—our need for “better smoking cessation” may simply reflect the need to use the tools we already have.
E-cigarettes may even have the potential to increase smoking rates in teenagers, with a recent study showing that e-cigarette use was associated with a 4-fold increase in tobacco cigarette smoking.
How would tight regulation work for e-cigarettes? There may be potential for restrictions to minimize the risks of e-cigarettes. Suggested restrictions include selling them only to adult smokers, childproof containers, appropriate labeling, electrical safety, and consumer advice.33,11 This would require vigorous oversight by agencies such as the FDA in the United States or the TGA in Australia. In August 2016, the FDA finalized a rule that extended its regulatory authority to cover a range of tobacco products, including e-cigarettes. Requirements include safety warnings and rules for retailers and manufacturers.34 Criticisms of the rule have included concerns about obstruction to safety modifications, reduced product innovation, and protection of tobacco cigarette sales through grandfathering of tobacco cigarettes.35 In Australia, e-cigarettes are currently unlawful for sale or personal use.36 Comprehensive regulation of standardized e-cigarettes seems some distance away.
By recommending e-cigarettes to lung cancer patients as a strategy for smoking cessation, does the physician undermine robust tobacco control? Good tobacco control, which drives down smoking rates, depends on multipronged strategies such as the MPOWER measures recommended by the WHO.37 Countries where these measures have been successfully introduced have shown a steady decline in smoking rates over the past few decades;38,39 such countries include those without high rates of e-cigarette use.38,40,41 E-cigarettes cannot be separated easily from the tobacco cigarette industry as the major international tobacco companies (including PMI, BAT, Lorillard, and Reynolds) have all purchased or developed e-cigarette brands since 2013.42 Does this matter for the lung cancer patient who smokes? In the short term, probably not. They just want to stop smoking and we, their physicians, want them to stop, too. We should avoid, however, any strategies that empower the tobacco industry through profit and that distract us (by the complexity of introducing e-cigarette regulations) from the real game of helping our patients finally quit.
No one can argue against smoking cessation in lung cancer patients. Many strategies are available to physicians, particularly to those who feel up-to-date in the field. But until (1) the safety data are mature, (2) e-cigarettes conform universally to tight regulatory standards, (3) e-cigarettes are no longer made by companies whose primary interest is profit from tobacco, and (4) there are no better alternatives, physicians should not routinely recommend them to their patients.✦
Opinion-Yes: K. Michael Cummings, PhD, MPH
Should clinicians recommend electronic cigarettes (e-cigarettes) to their lung cancer patients who continue to smoke? For many clinicians the answer to this question is a resounding NO WAY. However, I hope to persuade you that there are good reasons why clinicians should strongly consider recommending e-cigarettes to at least some of their patients who smoke.
It is not hard to understand why healthcare providers may be hesitant about recommending e-cigarettes to patients who continue to smoke, especially for those with a diagnosis of lung cancer. No e-cigarette has been officially licensed and marketed as an effective method to help someone stop smoking; in fact, some reviews suggest that e-cigarettes might actually hinder one’s ability to stop smoking.1,2 Additionally, it is hard to ignore the barrage of negative news stories about e-cigarettes: e.g., they can explode, there are cancer-causing chemicals in the vapor, the flavorings used in some of the products are attracting kids to use them, and big tobacco is pushing them as a way to keep people hooked and to attract a new generation of smokers.3-5 Finally, for patients with lung cancer, it seems illogical to consider recommending a product that involves inhaling vapor particles into already sensitive and damaged lungs.
Patients expect treatment guidance from their doctor. For those who smoke, the standard of care should include firm advice to stop smoking along with the provision of evidence-based treatment methods to address their nicotine dependence. 6 Treating nicotine dependence is exceedingly inexpensive compared to treating the consequences of not quitting, especially in those with lung cancer where continued smoking is known to increase risks for treatment-related complications, recurrence, and mortality. 7-10 Individual, group, and telephone counseling combined with 7 government- licensed stop smoking medications (i.e., nicotine replacement medications: gum, lozenge, patch, inhaler, and nasal spray; and non-nicotine medicines: varenicline [Chantix, Champix] and bupropion [Zyban, Wellbutrin]) have been shown to reliably increase quit rates over and above quitting without support (i.e., “cold turkey”).11,12
So why consider e-cigarettes as a treatment option? First, many patients have already tried the evidence-based methods and have found them to be unhelpful.13-16 Indeed, even with the best combination of evidence-based treatments, only about 1 in 5 smokers will be abstinent 6–12 months later.12 Most lung cancer patients do try to stop smoking when given the bad news about their cancer diagnosis, but a significant percentage relapse back to smoking.7,8 Mostly, what clinicians tell patients who have relapsed is to try harder to quit, often recommending the same failed treatment options again. Rarely does this work. If a patient’s cancer therapy fails to work, it would not be sound advice to recommend it keep being used; the same philosophy should apply to treating nicotine dependence.
Nicotine seeking is the primary motivation for continued smoking, so providing addicted smokers with an alternative that delivers nicotine without most of the harmful toxins in smoke makes sense.
Second, nicotine seeking is the primary motivation for continued smoking, so providing addicted smokers with an alternative that delivers nicotine without most of the harmful toxins in smoke makes sense.17 The problem with the licensed nicotine replacement medications is they provide too little nicotine too slowly to really satisfy smokers’ craving for nicotine when they try to abstain from smoking. Newer model e-cigarettes can deliver nicotine in a way that more closely mimics the nicotine delivery from a tobacco cigarette, which makes them attractive substitutes for cigarettes. 18,19 The improved nicotine delivery of newer e-cigarette devices may help explain conflicting scientific evidence on the effectiveness of e-cigarettes in stopping smoking. Many of the early studies of e-cigarettes were evaluating products that did not deliver nicotine effectively. Smokers in these studies rarely used the products frequently enough to get any benefit, and most returned to smoking. Studies with newer model e-cigarette devices are showing greater frequency of use by smokers and improved effectiveness for smoking cessation.20
Third, e-cigarettes are not lit, do not burn, and do not produce cigarette smoke. While e-cigarette vapor does include some of the same chemicals found in cigarette smoke, the levels of these chemicals are many-fold lower than found in cigarette smoke.21,22 So while e-cigarettes are not 100% safe, the risks are surely far lower than the alternative of inhaling cigarette smoke.23-25 It is also worth noting that several studies have found that smokers who switched from cigarettes to an e-cigarette had significantly improved lung function and lower risk of airway infection, which would be clinically important for someone with lung cancer.26-30
Fourth, many smokers prefer e-cigarettes over other aids to quitting. In England, a study tracking the use of stop smoking methods found that e-ciga rettes were the most popular method used.14 There are several reasons for the popularity of e-cigarettes as a stop smoking method, including the behavioral and sensory similarity to cigarette smoking, access to products that can be purchased at retail and online often at a lower cost compared to nicotine medications, effective product marketing with appealing flavors, and word of mouth from those who have successfully switched from smoking to “vaping.” The fact that e-cigarettes are not viewed as medicines and are used in much the same way as cigarettes may actually make them more attractive as substitutes for smoking compared, to licensed stop-smoking medicines. Additionally, with the wide variety of e-cigarette models now available, smokers have an opportunity to try different flavors and nicotine deliveries before settling on a device that best suits their needs. Two recent studies have found that smokers who purchased e-cigarettes from vape shops, where presumably they received some advice on the types of products available and how to vape, were more successful in quitting smoking compared to those who purchased e-cigarettes online or through a traditional tobacco selling retail outlet.31,32
Given the wide range of e-cigarette devices available and complexities associated with using them properly, it is not surprising that those getting instructions on which device might best suit their needs would fare better than those left to figure this out on their own.33 Currently, there are no standards for licensing vape shops or guidelines to ensure that the advice given to customers is accurate. However, unlike tobacco selling outlets that may also sell e-cigarettes, vape shops are in the business of selling only vaping products and are therefore motivated to help their customers switch away from cigarettes. Given the evolving and sometimes confusing science on e-cigarettes and the rapidly changing marketplace of nicotine delivery products, it is understandable why clinicians are hesitant to recommend e-cigarettes as an option to their patients trying to stop smoking.34 However, faced with the realities of nicotine addiction, the inadequacies of current evidencebased tobacco dependence treatments, and the dire consequences of continued smoking, uncertainty about e-cigarettes is no excuse for simply rejecting them. Clinicians have to make decisions based on the available evidence, which is nearly always incomplete. However, currently available evidence suggests a favorable risk-benefit profile for e-cigarette use in smokers who are otherwise unable to quit.23-25 Useful and credible guidance on how to talk to patients about e-cigarettes can be found in medical journals and online.35-39
What is important to recognize is that e-cigarettes are not a fad. Millions of people (including many cancer patients) are using them daily, and the marketplace of products is continuing to evolve. It would be unwise for clinicians to ignore this new technology that offers the potential to make cigarette smoking obsolete.40 ✦
Kenneth Michael Cummings, PhD, MPH, is coleader of the Tobacco Research Program at the Hollings Cancer Center, Medical University of South Carolina, US. A conflict of interest statement for Dr. Cummings is on file with the IASLC and available upon request.
References (Opinion-No: Emily Stone)
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2. Mason DP, Subramanian S, Nowicki ER, et al. Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study. Ann Thorac Surg. 2009;88(2):362-370; discussion 370-371.
3. Balduyck B, Nia PS, Cogen A, et al. The effect of smoking cessation on quality of life after lung cancer surgery. Eur J Cardiothorac Surg [Internet]. 2011 [cited 2016 Jan 26];40(6):1432-1438.
4. Mediratta N, Poullis M. Smoking status and 30-day mortality in patients undergoing pulmonary resections. Asian Cardiovasc Thorac Ann. 2016;24(7):663-669.
5. Roach MC, Rehman S, DeWees TA, Abraham CD, Bradley JD, Robinson CG. It’s never too late: smoking cessation after stereotactic body radiation therapy for non-small cell lung carcinoma improves overall survival. Pract Radiat Oncol. 2016;6(1):12-18.
6. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569.
7. Prochazka A, Koziol-McLain J, Tomlinson D, Lowenstein SR. Smoking cessation counseling by emergency physicians: opinions, knowledge, and training needs. Acad Emerg Med Off J Soc Acad Emerg Med. 1995;2(3):211-216.
8. Tong EK, Strouse R, Hall J, Kovac M, Schroeder SA. National survey of U.S. health professionals’ smoking prevalence, cessation practices, and beliefs. Nicotine Tob Res Off J Soc Res Nicotine Tob. 2010;12(7):724-733.
9. Weaver KE, Danhauer SC, Tooze JA, et al. Smoking cessation counseling beliefs and behaviors of outpatient oncology providers. The Oncologist. 2012;17(3):455–462.
10. Callahan-Lyon P. Electronic cigarettes: human health effects. Tob Control. 2014;23 Suppl 2:ii36-40.
11. Gartner CE, Hall WD, Borland R. How should we regulate smokeless tobacco products and e-cigarettes? Med J Aust. 2012;197(11):611-612.
12. Fiore MC, Jaén CR, Baker TB. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. 2008; Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008.
13. McNeill A, Brose LS, Calder R, Hitchman SC, Hajek P, McRobbie H. E-cigarettes: an evidence update. 2015; A report commissioned by Public Health England. Available from: https://www. gov.uk/government/uploads/system/uploads/ attachment_data/file/457102/Ecigarettes_an_ evidence_update_A_report_commissioned_by_ Public_Health_England_FINAL.pdf.
14. Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016;4(2):116-128. 15. El Dib R, Suzumura EA, Akl EA, et al. Electronic nicotine delivery systems and/or electronic nonnicotine delivery systems for tobacco smoking cessation or reduction: a systematic review and meta-analysis. BMJ Open. 2017;7(2):e012680.
16. Miech R, Patrick ME, O’Malley PM, Johnston LD. E-cigarette use as a predictor of cigarette smoking: results from a 1-year follow-up of a national sample of 12th grade students. Tob Control. 2017. pii: tobaccocontrol- 2016-053291. doi: 10.1136/tobaccocontrol- 2016-053291. [Epub ahead of print]
17. 7 Ways E-Cigarette Companies Are Copying Big Tobacco’s Playbook. Tobacco Unfiltered. Available from: http://www.tobaccofreekids.org/tobacco_ unfiltered/post/2013_10_02_ecigarettes.
18. Azzopardi D, Patel K, Jaunky T, et al. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke. Toxicol Mech Methods. 2016 Jul 23; 26(6): 477–491. 19. Czogala J, Goniewicz ML, Fidelus B, Zielinska- Danch W, Travers MJ, Sobczak A. Secondhand exposure to vapors from electronic cigarettes. Nicotine Tob Res. 2014;16(6):655-662.
20. Welz C, Canis M, Schwenk-Zieger S, et al. Cytotoxic and genotoxic effects of electronic cigarette liquids on human mucosal tissue cultures of the oropharynx. J Environ Pathol Toxicol Oncol. 2016;35:343-354.
21. Lerner CA, Sundar IK, Yao H, et al. Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung. PloS One. 2015;10(2):e0116732.
22. Dinakar C, O’Connor GT. The health effects of electronic cigarettes. N Engl J Med. 2016;375(26):2608- 2609.
23. Hess IM, Lachireddy K, Capon A. A systematic review of the health risks from passive exposure to electronic cigarette vapour. Public Health Res Pract. 2016;26(2).
24. Rudy SF, Durmowicz EL. Electronic nicotine delivery systems: overheating, fires and explosions. Tob Control. 2017;26:10-18.
25. Brownson EG, Thompson CM, Goldsberry S, et al. Explosion injuries from e-cigarettes. N Engl J Med. 2016;375(14):1400–1402.
26. Seo AD, Kim DC, Yu HJ, Kang MJ. Accidental ingestion of e-cigarette liquid nicotine in a 15-month-old child: an infant mortality case of nicotine intoxication. Korean J Pediatr. 2016;59(12):490-493.
27. Payne JD, Michaels D, Orellana-Barrios M, Nugent K. Electronic cigarette toxicity. J Prim Care Community Health. 2017;8(2):100-102.
28. NCCN. NCCN Guidelines for Smoking Cessation. Available from: https://www.nccn.org/about/news/ newsinfo.aspx?NewsID=498
29. RACGP Clinical Guidelines: Supporting Smoking Cessation – A Guide for Health Professionals. Available from: http://www.racgp.org.au/yourpractice/ guidelines/smoking-cessation/.
30. AHRQ. Treating Tobacco Use and Dependence: 2008 Update. Available from: /professionals/cliniciansproviders/ guidelines-recommendations/tobacco/ index.html. 31. Smoking Services | Guidance and Guidelines | NICE. Available from: https://www.nice.org.uk/guidance/ ph10?unlid=563156352016615154627. 32. Warren GW, Ostroff JS, Goffin JR. Lung cancer screening, cancer treatment, and addressing the continuum of health risks caused by tobacco. Am Soc Clin Oncol Educ Book Am Soc Clin Oncol Meet. 2016;35:223-239.
33. Mendelsohn CP. Electronic cigarettes: what can we learn from the UK experience? Med J Aust. 2016;204:14-15.
34. FDA. Vaporizers, E-Cigarettes and Other Electronic Nicotine Delivery Systems (ENDs). Available from: https://www.fda.gov/TobaccoProducts/ Labeling/ProductsIngredientsComponents/ ucm456610.htm.
35. Siegel M. POV: New FDA Regulations on Vaping Products a Failure. 2017. Available from: https:// www.bu.edu/today/2016/fda-vaping-regulations/.
36. Legal Status of Electronic Cigarettes in Australia [Internet]. 2016. Available from: http://www.quit. org.au/downloads/resource/policy-advocacy/ policy/legal-status-electronic-cigarettes-australia. pdf.
37. WHO | MPOWER [Internet]. WHO. Available from: http://www.who.int/tobacco/mpower/en/.
38. Schuler G, Adams V, Goto Y. Role of exercise in the prevention of cardiovascular disease: results, mechanisms, and new perspectives. Eur Heart J. 2013;34(24):1790-1799. 39. Samet JM. The Surgeon Generals’ reports and respiratory diseases. From 1964 to 2014. Ann Am Thorac Soc. 2014;11(2):141-148.
40. Australian Government Department of Health and Ageing. Tobacco Key Facts and Figures. Available from: http://www.health.gov.au/internet/main/ publishing.nsf/content/tobacco-kff.
41. Eichler M, Blettner M, Singer S. The use of e-cigarettes: a population-based cross-sectional survey of 4002 individuals in 2016. Dtsch Ärztebl Int. 2016;113(50):847.
42. Tobacco Tactics. Tobacco Tactics. E-cigarettes [Internet].Available from: http://www.tobaccotactics. org/index.php/E-cigarettes.
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2. El Dib R, Suzumura EA, Akl EA, et al. Electronic nicotine delivery systems and/or electronic nonnicotine delivery systems for tobacco smoking cessation or reduction: a systematic review and metaanalysis. BMJ Open. 2017;7:e012680. doi:10.1136/ bmjopen-2016-012680.
3. Rudy SF, Durmowicz EL. Electronic nicotine delivery systems: overheating, fires and explosions. Tob Control. 2017;26:10-18.
4. Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23:133-139.
5. Corey CG, Ambrose BK, Apelberg BJ, King BA. Flavored tobacco product use among middle and high school students–United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64:1066-1070.
6. Cummings KM, Dresler CM, Field JK, et al. E-cigarettes and cancer patients. J Thorac Oncol. 2014;9:438-441.
7. Cataldo JK, Dubey S, Prochaska JJ. Smoking cessation: an integral part of lung cancer treatment. Oncology. 2010;78:289-301.
8. Dobson Amato KA, Hyland A, et al. Tobacco cessation may improve lung cancer patient survival. J Thorac Oncol. 2015;10:1014-1019.
9. Warren GW, Kasza KA, Reid ME, Cummings KM, Marshall JR. Smoking at diagnosis and survival in cancer patients. Int J Cancer. 2013;132:401-410.
10. Warren GW, Alberg AJ, Kraft AS, Cummings KM. The 2014 Surgeon General’s report: “The health consequences of smoking–50 years of progress”: a paradigm shift in cancer care. Cancer. 2014;120:1914-1916.
11. Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A US Public Health Service report. Am J Prev Med. 2008;35:158-176.
12. West R, Raw M, McNeill A, et al. Health-care interventions to promote and assist tobacco cessation: a review of efficacy, effectiveness and affordability for use in national guideline development. Addiction. 2015;110:1388-1403.
13. Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V. Characteristics, perceived side effects and benefits of electronic cigarette use: a worldwide survey of more than 19,000 consumers. Int J Environ Res Public Health. 2014;11:4356-4373.
14. Beard E, West R, Michie S, Brown J. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends. BMJ. 2016;354:i4645.
15. Shahab L, Goniewicz M. Electronic cigarettes are at least as effective as nicotine patches for smoking cessation. Evid Based Med. 2014;19:133.
16. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382:1629-1637.
17. US Department of Health and Human Services. The Health Consequences of Smoking: Nicotine Addiction. A Report of the Surgeon General, 1988. DHHS; 1988. Report No.: Publication No. (CDC) 88-8406.
18. Hajek P, Przulj D, Phillips A, Anderson R, McRobbie H. Nicotine delivery to users from cigarettes and from different types of e-cigarettes. Psychopharmacology. 2017;234:773–779.
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21. Azzopardi D, Patel K, Jaunky T, et al. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke. Toxicol Mech Methods. 2016;26:477-491.
22. Shahab L, Goniewicz ML, Blount BC, et al. Nicotine, carcinogen, and toxin exposure in longterm e-cigarette and nicotine replacement therapy users: a cross-sectional study. Ann Intern Med. 2017;166(6):390-400.
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40. Abrams DB. Promise and peril of e-cigarettes: can disruptive technology make cigarettes obsolete? JAMA. 2014;311:135-136.