E-cigarettes: How “safe” are they?

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E-cigarettes: How “safe” are they?
PRACTICE RECOMMENDATIONS

› Inform patients that e-cigarette vapors contain toxic substances, including the heavy metals lead, cadmium, and nickel. A
› Educate all patients—particularly young people and those who are pregnant or lactating—about the potential health risks of e-cigarettes. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Electronic cigarettes (e-cigarettes) have become increasingly popular over the last decade. Although they are perceived by many to be safer than traditional cigarettes, many of the devices still contain nicotine, and inhaling their vapors exposes users to toxic substances, including lead, cadmium, and nickel—heavy metals that are associated with significant health problems.1 (For more on how e-cigarettes work, see “Cigarettes vs e-cigarettes: How does the experience (and cost) compare?”)

In addition, many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.2,3 They frequently end up utilizing both, increasing their health risks by exposing themselves to the dangers of 2 products instead of one.1

Further complicating the issue is that the manufacture and distribution of e-cigarettes has not been well regulated. Without regulation, there is no way to know with certainty how much nicotine the devices contain and what else is in them.

Things, however, are changing. The Food and Drug Administration (FDA) recently announced that e-cigarettes and other tobacco products like cigars and hookahs will now be regulated in the same way the government regulates tobacco cigarettes and smokeless tobacco.4 The rule will not take effect immediately because companies requested time to comply, but once it is enacted, packaging will be required to list what the products contain, among other changes.

Keeping up on the latest information on e-cigarettes is now—and will continue to be—important as family physicians are increasingly asked about them. What follows is a review of what we know about their potential risks.

 

© 2016 iStock

A nicotine system developed by a pharmacist

E-cigarettes, or electronic nicotine delivery systems, were patented in 2003 by a Chinese pharmacist.5 Since their introduction to North America and Europe in 2007, the devices have become known by over 400 different brand names.6 Consumption among adults doubled by 2012, and by 2014, about 4% of US adults used e-cigarettes every day or some days.7 Many of them are dual users of tobacco and electronic cigarettes. In fact, Jenkins and colleagues reports in this issue of JFP (see "E-cigarettes: Who's using them and why?") that over half of cigarette smokers (52%) in their study use e-cigarettes, usually to either lower their cigarette consumption or aid in smoking cessation. (Throughout this article, we will use “cigarettes” and “smoking” to refer to the use of traditional tobacco cigarettes.)

In addition to concern over an increase in use among the general population, there is significant concern about the increase in e-cigarette use among US middle and high school students.1,8,9 In 2015, e-cigarettes were the most commonly used smoking product among middle and high school students, with 620,000 middle school students and nearly 2.4 million high school students using the battery-powered devices in the past 30 days.10

Many factors have contributed to the growing popularity of e-cigarettes.

  • Perceived safety. With tobacco’s dangers so thoroughly documented, many advertising campaigns tout e-cigarettes as less dangerous than conventional cigarettes in terms of their ability to cause cardiac and lung diseases and low birth weights. This is largely because e-cigarettes do not produce the combustion products of tar, ash, or carbon monoxide. In addition, many consumers are mistakenly less fearful about the nicotine added to many e-cigarettes.
  • Expectation that it helps smokers quit. Many smokers view e-cigarettes as an aid to smoking cessation.6 In fact, testimonials of efficacy in tobacco cessation abound in promotional materials and on the Web, and e-cigarettes are recommended by some physicians as a means to quit or lessen smoking of tobacco cigarettes.11
  • Wide availability and opportunities for use. The use of electronic nicotine delivery devices is sometimes permitted in places where smoking of conventional cigarettes is banned, although rules vary widely in different parts of the country. In addition, e-cigarettes are readily available for purchase on the Internet without age verification.
  • Extensive advertising. There are increasing concerns that advertising campaigns unduly target adolescents, young adults, and women.12-155 In addition to advertising, the media and social influences play significant roles in young people’s experimentation with “vaping,” the term for inhaling electronic cigarette aerosols.14,15
  • Regulation, legislation remain controversial. Currently, e-cigarettes are not required to be tested before marketing,16 but that may change with the FDA’s new regulations. The British National Public Health body, Public Health England, has documented public health benefits of e-cigarettes when used as a way to quit smoking, and provides evidence that the devices are less dangerous than traditional cigarettes.17 But this issue and public policy are the subject of ongoing debate. In 2015, the United Kingdom made it illegal to sell e-cigarettes or e-liquids to people younger than 18 years of age and urged child-proof packaging.

What’s “in” an e-cigarette—and are the ingredients toxic?

Because e-cigarettes are relatively new to the global marketplace, little research exists regarding the long-term effects and safety of their use, especially among habitual users.

Vapor/refills. E-liquids may contain a variety of substances because they have been largely unregulated, but they generally include some combination of nicotine, propylene glycol, glycerin, and flavorings. In fact, up to 7000 flavors are available,6 including such kid-friendly flavors as chocolate, cherry crush, and bubble gum.

Since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

When the refills do contain nicotine, users generally derive less of the substance from the electronic devices than they do from a conventional cigarette. Researchers found that individual puffs from an e-cigarette contained 0 to 35 µg nicotine per puff.1,18 Assuming an amount at the high end of the spectrum (30 µg nicotine), it would take about 30 puffs of an e-cigarette to derive the same amount of nicotine (1 mg) typically delivered by a conventional cigarette.

The chemical make-up of the vapor and the biologic effects on animal models have been investigated using 42 different liquid refills.19,20 All contained potentially harmful compounds, but the levels were within exposure limits authorized by the FDA. These potentially dangerous chemicals include the known toxins formaldehyde, acrolein, and hydrocarbons.20

An inflammatory response to the inhalation of the vapors was demonstrated in mouse lungs; exposure to e-cigarette aerosols reduced lung glutathione—an important enzyme in maintaining oxidation-reduction balance—to a degree similar to that of cigarette smoke exposure.20 Less of the enzyme facilitates increased pulmonary inflammation.

In addition, human lung cells release pro-inflammatory cytokines when exposed to e-cigarette aerosols.20 Other health risks include:

Harm to indoor air quality/secondhand exposure. Even though e-cigarettes do not emit smoke, bystanders are exposed to the aerosol or vapor exhaled by the user, and researchers have found varying levels of such substances as formaldehyde, acetaldehyde, isoprene, acetic acid, acetone, propanol, propylene glycol, and nicotine in the air. However, it is unclear at this time whether the ultra-fine particles in the e-cigarette vapor have health effects commensurate with the emissions of conventional cigarettes.1,21,22

Cartridge refill ingestion by children. Accidental nicotine poisonings, particularly among children drawn to the colors, flavors, and scents of the e-liquids, have been problematic. In 2014, for example, over 3500 exposures occurred and more than half of those were in children younger than 6 years of age. (Exposure is defined as contact with the substance in some way including ingestion, inhalation, absorption by the skin/eyes, etc; not all exposures are poisonings or overdoses).23 Although incidence has tapered off somewhat, the American Association of Poison Control Centers reports that there were 623 exposures across all age groups between January 1, 2016 and April 30, 2016.23

Many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.

Environmental impact of discarded e-cigarettes. Discarded e-cigarettes filling our landfills is a new and emerging public health concern. Their batteries, as do all batteries, pollute the land and water and have the potential to leach lead into the environment.24 Similarly, incompletely used liquid cartridges and refills may contain nicotine and heavy metals, which add to these risks.24

Explosions. Fires and explosions have been documented with e-cigarette use, mostly due to malfunctioning lithium-ion batteries.25 Thermal injuries to the face and hands can be significant.

Heavy metals. The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is another area of significant concern, particularly for younger people who might have long-term exposure.1 All 3 heavy metals are known to be toxic to humans, and safe levels of inhalation have not been established.

Inhalation and/or ingestion of lead, in particular, can cause severe neurologic damage, especially to the developing brains of children.26 Lead also results in hematologic dysfunction. Because of the risks associated with inhalation of this heavy metal, the substance was removed from gasoline years ago.

Inhaled cadmium induces kidney, liver, bone, and respiratory tract pathology27 and can cause organ failure, hypertension, anemias, fractures, osteoporosis, and/or osteomalacia.28 And inhaling nickel produces an inflammatory pulmonary reaction.29

Pregnancy/lactation. Since no clear evidence exists on the safety of e-cigarette use during pregnancy, women should avoid exposure to these vapors during the entire perinatal period. Similarly, the effects of e-cigarettes on infants who are breastfeeding are not established. Pregnant and breastfeeding women should not replace cigarettes with e-cigarettes.30,31 For pregnant women who smoke, the US Preventive Services Task Force (USPSTF) advises using only behavioral methods to stop cigarette use.32 And until more information becomes available, exposing infants and young children to e-cigarette vapor during breastfeeding is not recommended.

On the flip side, without tobacco, tar, ash, or carbon monoxide, e-cigarettes may have some advantages when compared with the use of traditional cigarettes, but that has not been substantiated.

 

 

SIDEBAR
Cigarettes vs e-cigarettes: How does the experience (and cost) compare?

If you were to ask a smoker to describe how cigarette smoking compares to using e-cigarettes, he or she would probably tell you that while the process of drawing on an e-cigarette is similar to that of a conventional cigarette, the experience in terms of reaching that state of relaxation or getting that “smoker’s high” is not.

In fact, a recent national survey of current and former smokers found that more than three-quarters of current smokers (77%) rated e-cigarettes less satisfying than conventional cigarettes and stopped using them.1 “Being less harmful” was the most highly rated reason for continuing to use the devices among people who switched from conventional to e-cigarettes.

How do they work? E-cigarettes do not burn anything and users do not light them. E-cigarettes work in much the same way as a smoke or fog machine. They use battery power (usually a rechargeable lithium battery) to heat a solution—usually containing nicotine, flavorings, and other chemicals—to the point that it turns into vapor. Much of whatever substances are in the vapor enter the bloodstream through the buccal mucosa, rather than the lungs.

Devices typically have an on/off button or switch, an atomizer containing a heating coil, a battery, and an LED light, which is designed to simulate a burning cigarette. A sensor detects when a user takes a drag and activates the atomizer and light. Some of the devices can be charged with a USB cord.

Because e-cigarettes don’t burn anything, they don’t have any smoke. They also don’t have any tar, ash, carbon monoxide, or odor (except perhaps a faint, short-lived scent matching the flavor liquid chosen). But the issues of second-hand exposure and effects on air quality are still being investigated.

With over 500 brands available, devices generally fall into one of 3 categories:2

  • Cigalikes: About the same size and shape of a conventional cigarette, these cigarette look-alikes may come pre-filled with about a day’s worth of liquid and then may be discarded, or they may be non-disposable and have a replaceable cartridge.

     

 

  • eGo’s: Also known as "vape pens," these devices tend to be longer and wider than cigalikes, have a more powerful battery, and usually are refillable or have a replaceable cartridge.

  • Mods: Short for “modules,” these “vaporizers” tend to be the largest and most expensive type of e-cigarette. They may be refilled with e-liquid or accept replaceable cartridges and have even more powerful batteries.

What do they cost? A pack of cigarettes (containing 20 cigarettes) costs anywhere from $5 to $14, depending on where one lives.3 The price of e-cigarette devices starts at about $8 and can climb higher than $100. A 5-pack of flavor cartridges or a refill tank of e-liquid (which may last as long as about 150 cigarettes) costs about $10 to $15.4

To put this in perspective, a pack-a-day smoker in New York might spend about $5000 a year on cigarettes ($14 per pack x 365 days in a year), whereas someone who uses an e-cigarette device ($10) plus a refill tank per week ($14 x 52 weeks per year) will spend about $740 a year. (The actual cost will be higher because atomizers or devices as a whole must be replaced periodically, with some lasting only days and others lasting weeks or months, depending largely on how often one uses them. Although the cost of atomizers ranges widely, many can be found for $3-$5.)

Of course, the difference between cigarettes and e-cigarettes will be less dramatic in states where cigarettes are cheaper.

References

1.  Pechacek TF, Nayak P, Gregory KR, et al. The potential that electronic delivery systems can be a disruptive technology: results from a national survey. Nicotine Tob Res. 2016. Available at: http://ntr.oxfordjournals.org/content/early/2016/05/03/ntr.ntw102.abstract. Accessed May 13, 2016.

2.  Center for Environmental Health. A smoking gun: cancer-causing chemicals in e-cigarettes. Available at: http://www.ceh.org/wp-content/uploads/CEH-2015-report_A-Smoking-Gun_-Cancer-Causing-Chemicals-in-E-Cigarettes_alt.pdf. Accessed May 11, 2016.

3.  Holmes H. The price of being an American. What a pack of cigarettes costs, in every state. August 28, 2015. Available at: http://www.theawl.com/2015/08/what-a-pack-of-cigarettes-costs-in-every-state. Accessed May 11, 2016.

4.  Blu. How much do e-cigs cost? E-cig & vapor cigarette prices. Available at: http://www.blucigs.com/much-e-cigs-cost/. Accessed May 13, 2016.

 

 

Don’t substitute one form of nicotine for another

The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is an area of significant concern.

The USPSTF has not determined the benefit-to-harm ratio of using e-cigarettes as a smoking cessation aid, but recommends prescribing behavioral techniques and/or pharmacologic alternatives instead.32 Because the devices have been promoted as an aid to smoking cessation, intention to quit using tobacco products is a reason often stated for utilizing e-cigarettes.2,33,34 Indeed, use of e-cigarettes is much more likely among those who already utilize tobacco products.35-37

At least one study reports that e-cigarettes have efficacy similar to nicotine patches in achieving smoking abstinence among smokers who want to quit.38 Former smokers who used e-cigarettes to quit smoking reported fewer withdrawal symptoms than those who used nicotine skin patches.39 In addition, former smokers were more likely to endorse e-cigarettes than nicotine patches as a tobacco cigarette cessation aid. Significant reduction in tobacco smoke exposure has been demonstrated in dual users of tobacco and electronic cigarettes;40,41 however, both of these nicotine delivery systems sustain nicotine addiction.

Despite many ongoing studies to determine if e-cigarettes are useful as a smoking cessation aid, the results vary widely and are inconclusive at this time.42

E-cigarettes do not increase long-term tobacco abstinence

Contrary to popular belief, research shows that e-cigarette use among smokers is not associated with long-term tobacco abstinence.1 E-cigarette users, however, may make more attempts to quit smoking compared with smokers not using them.43 In addition, even though there is some evidence that e-cigarettes help smokers reduce the number of cigarettes smoked per day, simply reducing the daily number of cigarettes does not equate with safety.44 Smoking just one to 4 cigarettes per day poses 3 times the risk of myocardial infarction and lung cancer compared with not smoking.44 And since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

A gateway to other substances of abuse?

Pregnant and breastfeeding women should not replace tobacco cigarettes with e-cigarettes.

There is also fear that nicotine exposure via e-cigarettes, especially in young people, serves as a “gateway” to tobacco consumption and other substance abuses, and increases the risk for nicotine addiction.34 Such nicotine-induced effects are a result of changes in brain chemistry, and have been documented in humans and animals.34

These concerns about negative health consequences, combined with the fact that e-cigarettes are undocumented as a smoking cessation aid, add urgency to the need for legislative and regulatory actions that hopefully can curb all nicotine exposures, particularly for our nation’s youth. In the meantime, it is important for physicians to advise patients—and the public—about the risks of e-cigarettes and the importance of quitting all forms of nicotine inhalation because nicotine—regardless of how it is delivered—is still an addictive drug.

CORRESPONDENCE
Steven Lippmann, MD, University of Louisville School of Medicine, 401 E. Chestnut Street, Suite 610, Louisville, KY 40202; sblipp01@louisville.edu.

References

1. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129:1972-1986.

2. Vickerman KA, Carpenter KM, Altman T, et al. Use of electronic cigarettes among state tobacco cessation quitline callers. Nicotine Tob Res. 2013;15:1787-1791.

3. Grana R, Popova L, Ling P. A longitudinal analysis of electronic cigarette use and smoking cessation. JAMA Int Med. 2014;174:812-813.

4. U.S. Food and Drug Administration. Vaporizers, e-cigarettes, and other electronic nicotine delivery systems (ENDS). Available at: http://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm456610.htm. Accessed May 12, 2016.

5. Grana R, Benowitz N, Glantz SA. Background paper on E-cigarettes (electronic nicotine delivery systems). Center for Tobacco Control Research and Education, University of California, San Francisco, a WHO Collaborating Center on Tobacco Control. Prepared for World Health Organization Tobacco Free Initiative. December 2013. Available at: http://pvw.escholarship.org/uc/item/13p2b72n. Accessed March 31, 2014.

6. Zhu SH, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control. 2014;23:iii3-iii9.

7. Electronic Cigarette Use Among Adults: United States, 2014. NCHStats: A blog of the National Center for Health Statistics. Available at: http://nchstats.com/2015/10/28/electronic-cigarette-use-among-adults-united-states-2014/. Accessed April 22, 2016.

8. Centers for Disease Control and Prevention. E-cigarette use more than doubles among U.S. middle and high school students from 2011-2012. Available at: http://www.cdc.gov/media/releases/2013/p0905-ecigarette-use.html. Accessed April 22, 2016.

9. Centers for Disease Control and Prevention. Notes from the field: electronic cigarette use among middle and high school students — United States, 2011-2012. MMWR Morb Mortal Wkly Rep. 2013;62:729-730.

10. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students—United States, 2011-2015. MMWR Morb Mortal Wkly Rpt. 2016;65:361-367.

11. Kandra KL, Ranney LM, Lee JG, et al. Physicians’ attitudes and use of e-cigarettes as cessation devices, North Carolina, 2013. PloS One. 2014;9:e103462.

12. Schraufnagel DE. Electronic cigarettes: vulnerability of youth. Pediatr Allergy Immunol Pulmonol. 2015;28:2-6.

13. White J, Li J, Newcombe R, et al. Tripling use of electronic cigarettes among New Zealand adolescents between 2012 and 2014. J Adolesc Health. 2015;56:522-528.

14. Duke JC, Lee YO, Kim AE, et al. Exposure to electronic cigarette television advertisements among youth and young adults. Pediatrics. 2014;134:29-36.

15. Huang J, Kornfield R, Szczypka G, et al. A cross-sectional examination of marketing of electronic cigarettes on Twitter. Tob Control. 2014;23:iii26-iii30.

16. Rojewski AM, Coleman N, Toll BA. Position Statement: Emerging policy issues regarding electronic nicotine delivery systems: a need for regulation. Society of Behavioral Medicine. 2016. Available at: http://www.sbm.org/UserFiles/file/e-cig-statement_v2_lores.pdf. Accessed April 22, 2016.

17. McNeill A, Brose LS, Calder R, et al. E-cigarettes: an evidence update. A report commissioned by Public Health England. 2015. Available at: https://www.gov.uk/government/publications/e-cigarettes-an-evidence-update. Accessed April 22, 2016.

18. Goniewicz ML, Kuma T, Gawron M, et al. Nicotine levels in electronic cigarettes. Nicotine Tob Res. 2013;15:158-166.

19. Varlet V, Farsalinos K, Augsburger M, et al. Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health. 2015;12:4796-4815.

20. 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:e0116732.

21. Schober W, Szendrei K, Matzen W, et al. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health. 2014;217:628-637.

22. Schripp T, Markewitz D, Uhde E, et al. Does e-cigarette consumption cause passive vaping? Indoor Air. 2013;23:25-31.

23. The American Association of Poison Control Centers. E-cigarettes and liquid nicotine. Available at: http://www.aapcc.org/alerts/e-cigarettes/. Accessed May 12, 2016.

24. Krause MJ, Townsend TG. Hazardous waste status of discarded electronic cigarettes. Waste Manag. 2015;39:57-62.

25. U.S. Fire Administration. Electronic cigarette fires and explosions. October 2014. Available at: https://www.usfa.fema.gov/downloads/pdf/publications/electronic_cigarettes.pdf. Accessed May 17, 2016.

26. Skerfving S, Löfmark L, Lundh T, et al. Late effects of low blood lead concentrations in children on school performance and cognitive functions. Neurotoxicology. 2015;49:114-120.

27. Bernhoft RA. Cadmium toxicity and treatment. Scientific World Journal. 2013;394652.

28. Agency for Toxic Substances and Disease Registry. Case studies in environmental medicine (CSEM) Cadmium Toxicity. Available at: http://www.atsdr.cdc.gov/csem/cadmium/docs/cadmium.pdf. Accessed April 22, 2016.

29. Das KK, Buchner V. Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health. 2007;22:157-173.

30. England LJ, Bunnell RE, Pechacek TF, et al. Nicotine and the developing human: a neglected element in the electronic cigarette debate. Am J Prev Med. 2015;49:286-293.

31. Suter MA, Mastrobattista J, Sachs M, et al. Is there evidence for potential harm of electronic cigarette use in pregnancy? Birth defects research. Birth Defects Res A Clin Mol Teratol. 2015;103:186-195.

32. U.S. Preventive Services Task Force. Draft Recommendation Statement. Tobacco smoking cessation in adults and pregnant women: behavioral and pharmacotherapy interventions. Available at: http://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement147/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions1. Accessed March 22, 2016.

33. Peters EN, Harrell PT, Hendricks PS, et al. Electronic cigarettes in adults in outpatient substance use treatment: awareness, perceptions, use, and reasons for use. Am J Addict. 2015;24:233-239.

34. Kandel ER, Kandel DB. A molecular basis for nicotine as a gateway drug. N Engl J Med. 2014;371:932-943.

35. King BA, Patel R, Nguyen KH, et al. Trends in awareness and use of electronic cigarettes among US Adults, 2010-2013. Nicotine Tob Res. 2015;17:219-227.

36. McMillen RC, Gottlieb MA, Shaefer RM, et al. Trends in electronic cigarette use among U.S. adults: use is increasing in both smokers and nonsmokers. Nicotine Tob Res. 2015;1195-1202.

37. Lee S, Grana RA, Glantz SA. Electronic cigarette use among Korean adolescents: a cross-sectional study of market penetration, dual use, and relationship to quit attempts and former smoking. J Adolesc Health. 2014;54:684-690.

38. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382:1629-1637.

39. Nelson VA, Goniewicz ML, Beard E, et al. Comparison of the characteristics of long-term users of electronic cigarettes versus nicotine replacement therapy: a cross-sectional survey of English ex-smokers and current smokers. Drug Alcohol Depend. 2015;153:300-305.

40. Caponnetto P, Campagna D, Cibella F, et al. Efficiency and safety of an electronic cigarette (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013;8:e66317.

41. Polosa R, Caponnetto P, Morjaria JB, et al. Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health. 2011;11:786.

42. Malas M, van der Tempel J, Schwartz R, et al. Electronic cigarettes for smoking cessation: a systematic review. Nicotine Tob Res. 2016. [Epub ahead of print].

43. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110:1160-1168.

44. Bjartveit K, Tverdal A. Health consequences of smoking 1-4 cigarettes per day. Tob Control. 2005;14:315-320.

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Lee Smith, MD
Kanwarjeet Brar, MD
Kavitha Srinivasan, MD
Manasa Enja, MD
Steven Lippmann, MD

University of Louisville School of Medicine, Ky
sblipp01@louisville.edu

The authors reported no potential conflict of interest relevant to this article.

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Kanwarjeet Brar, MD
Kavitha Srinivasan, MD
Manasa Enja, MD
Steven Lippmann, MD

University of Louisville School of Medicine, Ky
sblipp01@louisville.edu

The authors reported no potential conflict of interest relevant to this article.

Author and Disclosure Information

Lee Smith, MD
Kanwarjeet Brar, MD
Kavitha Srinivasan, MD
Manasa Enja, MD
Steven Lippmann, MD

University of Louisville School of Medicine, Ky
sblipp01@louisville.edu

The authors reported no potential conflict of interest relevant to this article.

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Related Articles
PRACTICE RECOMMENDATIONS

› Inform patients that e-cigarette vapors contain toxic substances, including the heavy metals lead, cadmium, and nickel. A
› Educate all patients—particularly young people and those who are pregnant or lactating—about the potential health risks of e-cigarettes. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Electronic cigarettes (e-cigarettes) have become increasingly popular over the last decade. Although they are perceived by many to be safer than traditional cigarettes, many of the devices still contain nicotine, and inhaling their vapors exposes users to toxic substances, including lead, cadmium, and nickel—heavy metals that are associated with significant health problems.1 (For more on how e-cigarettes work, see “Cigarettes vs e-cigarettes: How does the experience (and cost) compare?”)

In addition, many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.2,3 They frequently end up utilizing both, increasing their health risks by exposing themselves to the dangers of 2 products instead of one.1

Further complicating the issue is that the manufacture and distribution of e-cigarettes has not been well regulated. Without regulation, there is no way to know with certainty how much nicotine the devices contain and what else is in them.

Things, however, are changing. The Food and Drug Administration (FDA) recently announced that e-cigarettes and other tobacco products like cigars and hookahs will now be regulated in the same way the government regulates tobacco cigarettes and smokeless tobacco.4 The rule will not take effect immediately because companies requested time to comply, but once it is enacted, packaging will be required to list what the products contain, among other changes.

Keeping up on the latest information on e-cigarettes is now—and will continue to be—important as family physicians are increasingly asked about them. What follows is a review of what we know about their potential risks.

 

© 2016 iStock

A nicotine system developed by a pharmacist

E-cigarettes, or electronic nicotine delivery systems, were patented in 2003 by a Chinese pharmacist.5 Since their introduction to North America and Europe in 2007, the devices have become known by over 400 different brand names.6 Consumption among adults doubled by 2012, and by 2014, about 4% of US adults used e-cigarettes every day or some days.7 Many of them are dual users of tobacco and electronic cigarettes. In fact, Jenkins and colleagues reports in this issue of JFP (see "E-cigarettes: Who's using them and why?") that over half of cigarette smokers (52%) in their study use e-cigarettes, usually to either lower their cigarette consumption or aid in smoking cessation. (Throughout this article, we will use “cigarettes” and “smoking” to refer to the use of traditional tobacco cigarettes.)

In addition to concern over an increase in use among the general population, there is significant concern about the increase in e-cigarette use among US middle and high school students.1,8,9 In 2015, e-cigarettes were the most commonly used smoking product among middle and high school students, with 620,000 middle school students and nearly 2.4 million high school students using the battery-powered devices in the past 30 days.10

Many factors have contributed to the growing popularity of e-cigarettes.

  • Perceived safety. With tobacco’s dangers so thoroughly documented, many advertising campaigns tout e-cigarettes as less dangerous than conventional cigarettes in terms of their ability to cause cardiac and lung diseases and low birth weights. This is largely because e-cigarettes do not produce the combustion products of tar, ash, or carbon monoxide. In addition, many consumers are mistakenly less fearful about the nicotine added to many e-cigarettes.
  • Expectation that it helps smokers quit. Many smokers view e-cigarettes as an aid to smoking cessation.6 In fact, testimonials of efficacy in tobacco cessation abound in promotional materials and on the Web, and e-cigarettes are recommended by some physicians as a means to quit or lessen smoking of tobacco cigarettes.11
  • Wide availability and opportunities for use. The use of electronic nicotine delivery devices is sometimes permitted in places where smoking of conventional cigarettes is banned, although rules vary widely in different parts of the country. In addition, e-cigarettes are readily available for purchase on the Internet without age verification.
  • Extensive advertising. There are increasing concerns that advertising campaigns unduly target adolescents, young adults, and women.12-155 In addition to advertising, the media and social influences play significant roles in young people’s experimentation with “vaping,” the term for inhaling electronic cigarette aerosols.14,15
  • Regulation, legislation remain controversial. Currently, e-cigarettes are not required to be tested before marketing,16 but that may change with the FDA’s new regulations. The British National Public Health body, Public Health England, has documented public health benefits of e-cigarettes when used as a way to quit smoking, and provides evidence that the devices are less dangerous than traditional cigarettes.17 But this issue and public policy are the subject of ongoing debate. In 2015, the United Kingdom made it illegal to sell e-cigarettes or e-liquids to people younger than 18 years of age and urged child-proof packaging.

What’s “in” an e-cigarette—and are the ingredients toxic?

Because e-cigarettes are relatively new to the global marketplace, little research exists regarding the long-term effects and safety of their use, especially among habitual users.

Vapor/refills. E-liquids may contain a variety of substances because they have been largely unregulated, but they generally include some combination of nicotine, propylene glycol, glycerin, and flavorings. In fact, up to 7000 flavors are available,6 including such kid-friendly flavors as chocolate, cherry crush, and bubble gum.

Since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

When the refills do contain nicotine, users generally derive less of the substance from the electronic devices than they do from a conventional cigarette. Researchers found that individual puffs from an e-cigarette contained 0 to 35 µg nicotine per puff.1,18 Assuming an amount at the high end of the spectrum (30 µg nicotine), it would take about 30 puffs of an e-cigarette to derive the same amount of nicotine (1 mg) typically delivered by a conventional cigarette.

The chemical make-up of the vapor and the biologic effects on animal models have been investigated using 42 different liquid refills.19,20 All contained potentially harmful compounds, but the levels were within exposure limits authorized by the FDA. These potentially dangerous chemicals include the known toxins formaldehyde, acrolein, and hydrocarbons.20

An inflammatory response to the inhalation of the vapors was demonstrated in mouse lungs; exposure to e-cigarette aerosols reduced lung glutathione—an important enzyme in maintaining oxidation-reduction balance—to a degree similar to that of cigarette smoke exposure.20 Less of the enzyme facilitates increased pulmonary inflammation.

In addition, human lung cells release pro-inflammatory cytokines when exposed to e-cigarette aerosols.20 Other health risks include:

Harm to indoor air quality/secondhand exposure. Even though e-cigarettes do not emit smoke, bystanders are exposed to the aerosol or vapor exhaled by the user, and researchers have found varying levels of such substances as formaldehyde, acetaldehyde, isoprene, acetic acid, acetone, propanol, propylene glycol, and nicotine in the air. However, it is unclear at this time whether the ultra-fine particles in the e-cigarette vapor have health effects commensurate with the emissions of conventional cigarettes.1,21,22

Cartridge refill ingestion by children. Accidental nicotine poisonings, particularly among children drawn to the colors, flavors, and scents of the e-liquids, have been problematic. In 2014, for example, over 3500 exposures occurred and more than half of those were in children younger than 6 years of age. (Exposure is defined as contact with the substance in some way including ingestion, inhalation, absorption by the skin/eyes, etc; not all exposures are poisonings or overdoses).23 Although incidence has tapered off somewhat, the American Association of Poison Control Centers reports that there were 623 exposures across all age groups between January 1, 2016 and April 30, 2016.23

Many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.

Environmental impact of discarded e-cigarettes. Discarded e-cigarettes filling our landfills is a new and emerging public health concern. Their batteries, as do all batteries, pollute the land and water and have the potential to leach lead into the environment.24 Similarly, incompletely used liquid cartridges and refills may contain nicotine and heavy metals, which add to these risks.24

Explosions. Fires and explosions have been documented with e-cigarette use, mostly due to malfunctioning lithium-ion batteries.25 Thermal injuries to the face and hands can be significant.

Heavy metals. The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is another area of significant concern, particularly for younger people who might have long-term exposure.1 All 3 heavy metals are known to be toxic to humans, and safe levels of inhalation have not been established.

Inhalation and/or ingestion of lead, in particular, can cause severe neurologic damage, especially to the developing brains of children.26 Lead also results in hematologic dysfunction. Because of the risks associated with inhalation of this heavy metal, the substance was removed from gasoline years ago.

Inhaled cadmium induces kidney, liver, bone, and respiratory tract pathology27 and can cause organ failure, hypertension, anemias, fractures, osteoporosis, and/or osteomalacia.28 And inhaling nickel produces an inflammatory pulmonary reaction.29

Pregnancy/lactation. Since no clear evidence exists on the safety of e-cigarette use during pregnancy, women should avoid exposure to these vapors during the entire perinatal period. Similarly, the effects of e-cigarettes on infants who are breastfeeding are not established. Pregnant and breastfeeding women should not replace cigarettes with e-cigarettes.30,31 For pregnant women who smoke, the US Preventive Services Task Force (USPSTF) advises using only behavioral methods to stop cigarette use.32 And until more information becomes available, exposing infants and young children to e-cigarette vapor during breastfeeding is not recommended.

On the flip side, without tobacco, tar, ash, or carbon monoxide, e-cigarettes may have some advantages when compared with the use of traditional cigarettes, but that has not been substantiated.

 

 

SIDEBAR
Cigarettes vs e-cigarettes: How does the experience (and cost) compare?

If you were to ask a smoker to describe how cigarette smoking compares to using e-cigarettes, he or she would probably tell you that while the process of drawing on an e-cigarette is similar to that of a conventional cigarette, the experience in terms of reaching that state of relaxation or getting that “smoker’s high” is not.

In fact, a recent national survey of current and former smokers found that more than three-quarters of current smokers (77%) rated e-cigarettes less satisfying than conventional cigarettes and stopped using them.1 “Being less harmful” was the most highly rated reason for continuing to use the devices among people who switched from conventional to e-cigarettes.

How do they work? E-cigarettes do not burn anything and users do not light them. E-cigarettes work in much the same way as a smoke or fog machine. They use battery power (usually a rechargeable lithium battery) to heat a solution—usually containing nicotine, flavorings, and other chemicals—to the point that it turns into vapor. Much of whatever substances are in the vapor enter the bloodstream through the buccal mucosa, rather than the lungs.

Devices typically have an on/off button or switch, an atomizer containing a heating coil, a battery, and an LED light, which is designed to simulate a burning cigarette. A sensor detects when a user takes a drag and activates the atomizer and light. Some of the devices can be charged with a USB cord.

Because e-cigarettes don’t burn anything, they don’t have any smoke. They also don’t have any tar, ash, carbon monoxide, or odor (except perhaps a faint, short-lived scent matching the flavor liquid chosen). But the issues of second-hand exposure and effects on air quality are still being investigated.

With over 500 brands available, devices generally fall into one of 3 categories:2

  • Cigalikes: About the same size and shape of a conventional cigarette, these cigarette look-alikes may come pre-filled with about a day’s worth of liquid and then may be discarded, or they may be non-disposable and have a replaceable cartridge.

     

 

  • eGo’s: Also known as "vape pens," these devices tend to be longer and wider than cigalikes, have a more powerful battery, and usually are refillable or have a replaceable cartridge.

  • Mods: Short for “modules,” these “vaporizers” tend to be the largest and most expensive type of e-cigarette. They may be refilled with e-liquid or accept replaceable cartridges and have even more powerful batteries.

What do they cost? A pack of cigarettes (containing 20 cigarettes) costs anywhere from $5 to $14, depending on where one lives.3 The price of e-cigarette devices starts at about $8 and can climb higher than $100. A 5-pack of flavor cartridges or a refill tank of e-liquid (which may last as long as about 150 cigarettes) costs about $10 to $15.4

To put this in perspective, a pack-a-day smoker in New York might spend about $5000 a year on cigarettes ($14 per pack x 365 days in a year), whereas someone who uses an e-cigarette device ($10) plus a refill tank per week ($14 x 52 weeks per year) will spend about $740 a year. (The actual cost will be higher because atomizers or devices as a whole must be replaced periodically, with some lasting only days and others lasting weeks or months, depending largely on how often one uses them. Although the cost of atomizers ranges widely, many can be found for $3-$5.)

Of course, the difference between cigarettes and e-cigarettes will be less dramatic in states where cigarettes are cheaper.

References

1.  Pechacek TF, Nayak P, Gregory KR, et al. The potential that electronic delivery systems can be a disruptive technology: results from a national survey. Nicotine Tob Res. 2016. Available at: http://ntr.oxfordjournals.org/content/early/2016/05/03/ntr.ntw102.abstract. Accessed May 13, 2016.

2.  Center for Environmental Health. A smoking gun: cancer-causing chemicals in e-cigarettes. Available at: http://www.ceh.org/wp-content/uploads/CEH-2015-report_A-Smoking-Gun_-Cancer-Causing-Chemicals-in-E-Cigarettes_alt.pdf. Accessed May 11, 2016.

3.  Holmes H. The price of being an American. What a pack of cigarettes costs, in every state. August 28, 2015. Available at: http://www.theawl.com/2015/08/what-a-pack-of-cigarettes-costs-in-every-state. Accessed May 11, 2016.

4.  Blu. How much do e-cigs cost? E-cig & vapor cigarette prices. Available at: http://www.blucigs.com/much-e-cigs-cost/. Accessed May 13, 2016.

 

 

Don’t substitute one form of nicotine for another

The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is an area of significant concern.

The USPSTF has not determined the benefit-to-harm ratio of using e-cigarettes as a smoking cessation aid, but recommends prescribing behavioral techniques and/or pharmacologic alternatives instead.32 Because the devices have been promoted as an aid to smoking cessation, intention to quit using tobacco products is a reason often stated for utilizing e-cigarettes.2,33,34 Indeed, use of e-cigarettes is much more likely among those who already utilize tobacco products.35-37

At least one study reports that e-cigarettes have efficacy similar to nicotine patches in achieving smoking abstinence among smokers who want to quit.38 Former smokers who used e-cigarettes to quit smoking reported fewer withdrawal symptoms than those who used nicotine skin patches.39 In addition, former smokers were more likely to endorse e-cigarettes than nicotine patches as a tobacco cigarette cessation aid. Significant reduction in tobacco smoke exposure has been demonstrated in dual users of tobacco and electronic cigarettes;40,41 however, both of these nicotine delivery systems sustain nicotine addiction.

Despite many ongoing studies to determine if e-cigarettes are useful as a smoking cessation aid, the results vary widely and are inconclusive at this time.42

E-cigarettes do not increase long-term tobacco abstinence

Contrary to popular belief, research shows that e-cigarette use among smokers is not associated with long-term tobacco abstinence.1 E-cigarette users, however, may make more attempts to quit smoking compared with smokers not using them.43 In addition, even though there is some evidence that e-cigarettes help smokers reduce the number of cigarettes smoked per day, simply reducing the daily number of cigarettes does not equate with safety.44 Smoking just one to 4 cigarettes per day poses 3 times the risk of myocardial infarction and lung cancer compared with not smoking.44 And since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

A gateway to other substances of abuse?

Pregnant and breastfeeding women should not replace tobacco cigarettes with e-cigarettes.

There is also fear that nicotine exposure via e-cigarettes, especially in young people, serves as a “gateway” to tobacco consumption and other substance abuses, and increases the risk for nicotine addiction.34 Such nicotine-induced effects are a result of changes in brain chemistry, and have been documented in humans and animals.34

These concerns about negative health consequences, combined with the fact that e-cigarettes are undocumented as a smoking cessation aid, add urgency to the need for legislative and regulatory actions that hopefully can curb all nicotine exposures, particularly for our nation’s youth. In the meantime, it is important for physicians to advise patients—and the public—about the risks of e-cigarettes and the importance of quitting all forms of nicotine inhalation because nicotine—regardless of how it is delivered—is still an addictive drug.

CORRESPONDENCE
Steven Lippmann, MD, University of Louisville School of Medicine, 401 E. Chestnut Street, Suite 610, Louisville, KY 40202; sblipp01@louisville.edu.

PRACTICE RECOMMENDATIONS

› Inform patients that e-cigarette vapors contain toxic substances, including the heavy metals lead, cadmium, and nickel. A
› Educate all patients—particularly young people and those who are pregnant or lactating—about the potential health risks of e-cigarettes. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Electronic cigarettes (e-cigarettes) have become increasingly popular over the last decade. Although they are perceived by many to be safer than traditional cigarettes, many of the devices still contain nicotine, and inhaling their vapors exposes users to toxic substances, including lead, cadmium, and nickel—heavy metals that are associated with significant health problems.1 (For more on how e-cigarettes work, see “Cigarettes vs e-cigarettes: How does the experience (and cost) compare?”)

In addition, many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.2,3 They frequently end up utilizing both, increasing their health risks by exposing themselves to the dangers of 2 products instead of one.1

Further complicating the issue is that the manufacture and distribution of e-cigarettes has not been well regulated. Without regulation, there is no way to know with certainty how much nicotine the devices contain and what else is in them.

Things, however, are changing. The Food and Drug Administration (FDA) recently announced that e-cigarettes and other tobacco products like cigars and hookahs will now be regulated in the same way the government regulates tobacco cigarettes and smokeless tobacco.4 The rule will not take effect immediately because companies requested time to comply, but once it is enacted, packaging will be required to list what the products contain, among other changes.

Keeping up on the latest information on e-cigarettes is now—and will continue to be—important as family physicians are increasingly asked about them. What follows is a review of what we know about their potential risks.

 

© 2016 iStock

A nicotine system developed by a pharmacist

E-cigarettes, or electronic nicotine delivery systems, were patented in 2003 by a Chinese pharmacist.5 Since their introduction to North America and Europe in 2007, the devices have become known by over 400 different brand names.6 Consumption among adults doubled by 2012, and by 2014, about 4% of US adults used e-cigarettes every day or some days.7 Many of them are dual users of tobacco and electronic cigarettes. In fact, Jenkins and colleagues reports in this issue of JFP (see "E-cigarettes: Who's using them and why?") that over half of cigarette smokers (52%) in their study use e-cigarettes, usually to either lower their cigarette consumption or aid in smoking cessation. (Throughout this article, we will use “cigarettes” and “smoking” to refer to the use of traditional tobacco cigarettes.)

In addition to concern over an increase in use among the general population, there is significant concern about the increase in e-cigarette use among US middle and high school students.1,8,9 In 2015, e-cigarettes were the most commonly used smoking product among middle and high school students, with 620,000 middle school students and nearly 2.4 million high school students using the battery-powered devices in the past 30 days.10

Many factors have contributed to the growing popularity of e-cigarettes.

  • Perceived safety. With tobacco’s dangers so thoroughly documented, many advertising campaigns tout e-cigarettes as less dangerous than conventional cigarettes in terms of their ability to cause cardiac and lung diseases and low birth weights. This is largely because e-cigarettes do not produce the combustion products of tar, ash, or carbon monoxide. In addition, many consumers are mistakenly less fearful about the nicotine added to many e-cigarettes.
  • Expectation that it helps smokers quit. Many smokers view e-cigarettes as an aid to smoking cessation.6 In fact, testimonials of efficacy in tobacco cessation abound in promotional materials and on the Web, and e-cigarettes are recommended by some physicians as a means to quit or lessen smoking of tobacco cigarettes.11
  • Wide availability and opportunities for use. The use of electronic nicotine delivery devices is sometimes permitted in places where smoking of conventional cigarettes is banned, although rules vary widely in different parts of the country. In addition, e-cigarettes are readily available for purchase on the Internet without age verification.
  • Extensive advertising. There are increasing concerns that advertising campaigns unduly target adolescents, young adults, and women.12-155 In addition to advertising, the media and social influences play significant roles in young people’s experimentation with “vaping,” the term for inhaling electronic cigarette aerosols.14,15
  • Regulation, legislation remain controversial. Currently, e-cigarettes are not required to be tested before marketing,16 but that may change with the FDA’s new regulations. The British National Public Health body, Public Health England, has documented public health benefits of e-cigarettes when used as a way to quit smoking, and provides evidence that the devices are less dangerous than traditional cigarettes.17 But this issue and public policy are the subject of ongoing debate. In 2015, the United Kingdom made it illegal to sell e-cigarettes or e-liquids to people younger than 18 years of age and urged child-proof packaging.

What’s “in” an e-cigarette—and are the ingredients toxic?

Because e-cigarettes are relatively new to the global marketplace, little research exists regarding the long-term effects and safety of their use, especially among habitual users.

Vapor/refills. E-liquids may contain a variety of substances because they have been largely unregulated, but they generally include some combination of nicotine, propylene glycol, glycerin, and flavorings. In fact, up to 7000 flavors are available,6 including such kid-friendly flavors as chocolate, cherry crush, and bubble gum.

Since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

When the refills do contain nicotine, users generally derive less of the substance from the electronic devices than they do from a conventional cigarette. Researchers found that individual puffs from an e-cigarette contained 0 to 35 µg nicotine per puff.1,18 Assuming an amount at the high end of the spectrum (30 µg nicotine), it would take about 30 puffs of an e-cigarette to derive the same amount of nicotine (1 mg) typically delivered by a conventional cigarette.

The chemical make-up of the vapor and the biologic effects on animal models have been investigated using 42 different liquid refills.19,20 All contained potentially harmful compounds, but the levels were within exposure limits authorized by the FDA. These potentially dangerous chemicals include the known toxins formaldehyde, acrolein, and hydrocarbons.20

An inflammatory response to the inhalation of the vapors was demonstrated in mouse lungs; exposure to e-cigarette aerosols reduced lung glutathione—an important enzyme in maintaining oxidation-reduction balance—to a degree similar to that of cigarette smoke exposure.20 Less of the enzyme facilitates increased pulmonary inflammation.

In addition, human lung cells release pro-inflammatory cytokines when exposed to e-cigarette aerosols.20 Other health risks include:

Harm to indoor air quality/secondhand exposure. Even though e-cigarettes do not emit smoke, bystanders are exposed to the aerosol or vapor exhaled by the user, and researchers have found varying levels of such substances as formaldehyde, acetaldehyde, isoprene, acetic acid, acetone, propanol, propylene glycol, and nicotine in the air. However, it is unclear at this time whether the ultra-fine particles in the e-cigarette vapor have health effects commensurate with the emissions of conventional cigarettes.1,21,22

Cartridge refill ingestion by children. Accidental nicotine poisonings, particularly among children drawn to the colors, flavors, and scents of the e-liquids, have been problematic. In 2014, for example, over 3500 exposures occurred and more than half of those were in children younger than 6 years of age. (Exposure is defined as contact with the substance in some way including ingestion, inhalation, absorption by the skin/eyes, etc; not all exposures are poisonings or overdoses).23 Although incidence has tapered off somewhat, the American Association of Poison Control Centers reports that there were 623 exposures across all age groups between January 1, 2016 and April 30, 2016.23

Many people use e-cigarettes as a means to stop smoking, but few who do so achieve abstinence.

Environmental impact of discarded e-cigarettes. Discarded e-cigarettes filling our landfills is a new and emerging public health concern. Their batteries, as do all batteries, pollute the land and water and have the potential to leach lead into the environment.24 Similarly, incompletely used liquid cartridges and refills may contain nicotine and heavy metals, which add to these risks.24

Explosions. Fires and explosions have been documented with e-cigarette use, mostly due to malfunctioning lithium-ion batteries.25 Thermal injuries to the face and hands can be significant.

Heavy metals. The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is another area of significant concern, particularly for younger people who might have long-term exposure.1 All 3 heavy metals are known to be toxic to humans, and safe levels of inhalation have not been established.

Inhalation and/or ingestion of lead, in particular, can cause severe neurologic damage, especially to the developing brains of children.26 Lead also results in hematologic dysfunction. Because of the risks associated with inhalation of this heavy metal, the substance was removed from gasoline years ago.

Inhaled cadmium induces kidney, liver, bone, and respiratory tract pathology27 and can cause organ failure, hypertension, anemias, fractures, osteoporosis, and/or osteomalacia.28 And inhaling nickel produces an inflammatory pulmonary reaction.29

Pregnancy/lactation. Since no clear evidence exists on the safety of e-cigarette use during pregnancy, women should avoid exposure to these vapors during the entire perinatal period. Similarly, the effects of e-cigarettes on infants who are breastfeeding are not established. Pregnant and breastfeeding women should not replace cigarettes with e-cigarettes.30,31 For pregnant women who smoke, the US Preventive Services Task Force (USPSTF) advises using only behavioral methods to stop cigarette use.32 And until more information becomes available, exposing infants and young children to e-cigarette vapor during breastfeeding is not recommended.

On the flip side, without tobacco, tar, ash, or carbon monoxide, e-cigarettes may have some advantages when compared with the use of traditional cigarettes, but that has not been substantiated.

 

 

SIDEBAR
Cigarettes vs e-cigarettes: How does the experience (and cost) compare?

If you were to ask a smoker to describe how cigarette smoking compares to using e-cigarettes, he or she would probably tell you that while the process of drawing on an e-cigarette is similar to that of a conventional cigarette, the experience in terms of reaching that state of relaxation or getting that “smoker’s high” is not.

In fact, a recent national survey of current and former smokers found that more than three-quarters of current smokers (77%) rated e-cigarettes less satisfying than conventional cigarettes and stopped using them.1 “Being less harmful” was the most highly rated reason for continuing to use the devices among people who switched from conventional to e-cigarettes.

How do they work? E-cigarettes do not burn anything and users do not light them. E-cigarettes work in much the same way as a smoke or fog machine. They use battery power (usually a rechargeable lithium battery) to heat a solution—usually containing nicotine, flavorings, and other chemicals—to the point that it turns into vapor. Much of whatever substances are in the vapor enter the bloodstream through the buccal mucosa, rather than the lungs.

Devices typically have an on/off button or switch, an atomizer containing a heating coil, a battery, and an LED light, which is designed to simulate a burning cigarette. A sensor detects when a user takes a drag and activates the atomizer and light. Some of the devices can be charged with a USB cord.

Because e-cigarettes don’t burn anything, they don’t have any smoke. They also don’t have any tar, ash, carbon monoxide, or odor (except perhaps a faint, short-lived scent matching the flavor liquid chosen). But the issues of second-hand exposure and effects on air quality are still being investigated.

With over 500 brands available, devices generally fall into one of 3 categories:2

  • Cigalikes: About the same size and shape of a conventional cigarette, these cigarette look-alikes may come pre-filled with about a day’s worth of liquid and then may be discarded, or they may be non-disposable and have a replaceable cartridge.

     

 

  • eGo’s: Also known as "vape pens," these devices tend to be longer and wider than cigalikes, have a more powerful battery, and usually are refillable or have a replaceable cartridge.

  • Mods: Short for “modules,” these “vaporizers” tend to be the largest and most expensive type of e-cigarette. They may be refilled with e-liquid or accept replaceable cartridges and have even more powerful batteries.

What do they cost? A pack of cigarettes (containing 20 cigarettes) costs anywhere from $5 to $14, depending on where one lives.3 The price of e-cigarette devices starts at about $8 and can climb higher than $100. A 5-pack of flavor cartridges or a refill tank of e-liquid (which may last as long as about 150 cigarettes) costs about $10 to $15.4

To put this in perspective, a pack-a-day smoker in New York might spend about $5000 a year on cigarettes ($14 per pack x 365 days in a year), whereas someone who uses an e-cigarette device ($10) plus a refill tank per week ($14 x 52 weeks per year) will spend about $740 a year. (The actual cost will be higher because atomizers or devices as a whole must be replaced periodically, with some lasting only days and others lasting weeks or months, depending largely on how often one uses them. Although the cost of atomizers ranges widely, many can be found for $3-$5.)

Of course, the difference between cigarettes and e-cigarettes will be less dramatic in states where cigarettes are cheaper.

References

1.  Pechacek TF, Nayak P, Gregory KR, et al. The potential that electronic delivery systems can be a disruptive technology: results from a national survey. Nicotine Tob Res. 2016. Available at: http://ntr.oxfordjournals.org/content/early/2016/05/03/ntr.ntw102.abstract. Accessed May 13, 2016.

2.  Center for Environmental Health. A smoking gun: cancer-causing chemicals in e-cigarettes. Available at: http://www.ceh.org/wp-content/uploads/CEH-2015-report_A-Smoking-Gun_-Cancer-Causing-Chemicals-in-E-Cigarettes_alt.pdf. Accessed May 11, 2016.

3.  Holmes H. The price of being an American. What a pack of cigarettes costs, in every state. August 28, 2015. Available at: http://www.theawl.com/2015/08/what-a-pack-of-cigarettes-costs-in-every-state. Accessed May 11, 2016.

4.  Blu. How much do e-cigs cost? E-cig & vapor cigarette prices. Available at: http://www.blucigs.com/much-e-cigs-cost/. Accessed May 13, 2016.

 

 

Don’t substitute one form of nicotine for another

The presence of lead, cadmium, and nickel in inhaled e-cigarette vapor is an area of significant concern.

The USPSTF has not determined the benefit-to-harm ratio of using e-cigarettes as a smoking cessation aid, but recommends prescribing behavioral techniques and/or pharmacologic alternatives instead.32 Because the devices have been promoted as an aid to smoking cessation, intention to quit using tobacco products is a reason often stated for utilizing e-cigarettes.2,33,34 Indeed, use of e-cigarettes is much more likely among those who already utilize tobacco products.35-37

At least one study reports that e-cigarettes have efficacy similar to nicotine patches in achieving smoking abstinence among smokers who want to quit.38 Former smokers who used e-cigarettes to quit smoking reported fewer withdrawal symptoms than those who used nicotine skin patches.39 In addition, former smokers were more likely to endorse e-cigarettes than nicotine patches as a tobacco cigarette cessation aid. Significant reduction in tobacco smoke exposure has been demonstrated in dual users of tobacco and electronic cigarettes;40,41 however, both of these nicotine delivery systems sustain nicotine addiction.

Despite many ongoing studies to determine if e-cigarettes are useful as a smoking cessation aid, the results vary widely and are inconclusive at this time.42

E-cigarettes do not increase long-term tobacco abstinence

Contrary to popular belief, research shows that e-cigarette use among smokers is not associated with long-term tobacco abstinence.1 E-cigarette users, however, may make more attempts to quit smoking compared with smokers not using them.43 In addition, even though there is some evidence that e-cigarettes help smokers reduce the number of cigarettes smoked per day, simply reducing the daily number of cigarettes does not equate with safety.44 Smoking just one to 4 cigarettes per day poses 3 times the risk of myocardial infarction and lung cancer compared with not smoking.44 And since many individuals continue to use traditional and electronic cigarettes, they end up in double jeopardy of toxicity through exposure to the dangers of both.

A gateway to other substances of abuse?

Pregnant and breastfeeding women should not replace tobacco cigarettes with e-cigarettes.

There is also fear that nicotine exposure via e-cigarettes, especially in young people, serves as a “gateway” to tobacco consumption and other substance abuses, and increases the risk for nicotine addiction.34 Such nicotine-induced effects are a result of changes in brain chemistry, and have been documented in humans and animals.34

These concerns about negative health consequences, combined with the fact that e-cigarettes are undocumented as a smoking cessation aid, add urgency to the need for legislative and regulatory actions that hopefully can curb all nicotine exposures, particularly for our nation’s youth. In the meantime, it is important for physicians to advise patients—and the public—about the risks of e-cigarettes and the importance of quitting all forms of nicotine inhalation because nicotine—regardless of how it is delivered—is still an addictive drug.

CORRESPONDENCE
Steven Lippmann, MD, University of Louisville School of Medicine, 401 E. Chestnut Street, Suite 610, Louisville, KY 40202; sblipp01@louisville.edu.

References

1. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129:1972-1986.

2. Vickerman KA, Carpenter KM, Altman T, et al. Use of electronic cigarettes among state tobacco cessation quitline callers. Nicotine Tob Res. 2013;15:1787-1791.

3. Grana R, Popova L, Ling P. A longitudinal analysis of electronic cigarette use and smoking cessation. JAMA Int Med. 2014;174:812-813.

4. U.S. Food and Drug Administration. Vaporizers, e-cigarettes, and other electronic nicotine delivery systems (ENDS). Available at: http://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm456610.htm. Accessed May 12, 2016.

5. Grana R, Benowitz N, Glantz SA. Background paper on E-cigarettes (electronic nicotine delivery systems). Center for Tobacco Control Research and Education, University of California, San Francisco, a WHO Collaborating Center on Tobacco Control. Prepared for World Health Organization Tobacco Free Initiative. December 2013. Available at: http://pvw.escholarship.org/uc/item/13p2b72n. Accessed March 31, 2014.

6. Zhu SH, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control. 2014;23:iii3-iii9.

7. Electronic Cigarette Use Among Adults: United States, 2014. NCHStats: A blog of the National Center for Health Statistics. Available at: http://nchstats.com/2015/10/28/electronic-cigarette-use-among-adults-united-states-2014/. Accessed April 22, 2016.

8. Centers for Disease Control and Prevention. E-cigarette use more than doubles among U.S. middle and high school students from 2011-2012. Available at: http://www.cdc.gov/media/releases/2013/p0905-ecigarette-use.html. Accessed April 22, 2016.

9. Centers for Disease Control and Prevention. Notes from the field: electronic cigarette use among middle and high school students — United States, 2011-2012. MMWR Morb Mortal Wkly Rep. 2013;62:729-730.

10. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students—United States, 2011-2015. MMWR Morb Mortal Wkly Rpt. 2016;65:361-367.

11. Kandra KL, Ranney LM, Lee JG, et al. Physicians’ attitudes and use of e-cigarettes as cessation devices, North Carolina, 2013. PloS One. 2014;9:e103462.

12. Schraufnagel DE. Electronic cigarettes: vulnerability of youth. Pediatr Allergy Immunol Pulmonol. 2015;28:2-6.

13. White J, Li J, Newcombe R, et al. Tripling use of electronic cigarettes among New Zealand adolescents between 2012 and 2014. J Adolesc Health. 2015;56:522-528.

14. Duke JC, Lee YO, Kim AE, et al. Exposure to electronic cigarette television advertisements among youth and young adults. Pediatrics. 2014;134:29-36.

15. Huang J, Kornfield R, Szczypka G, et al. A cross-sectional examination of marketing of electronic cigarettes on Twitter. Tob Control. 2014;23:iii26-iii30.

16. Rojewski AM, Coleman N, Toll BA. Position Statement: Emerging policy issues regarding electronic nicotine delivery systems: a need for regulation. Society of Behavioral Medicine. 2016. Available at: http://www.sbm.org/UserFiles/file/e-cig-statement_v2_lores.pdf. Accessed April 22, 2016.

17. McNeill A, Brose LS, Calder R, et al. E-cigarettes: an evidence update. A report commissioned by Public Health England. 2015. Available at: https://www.gov.uk/government/publications/e-cigarettes-an-evidence-update. Accessed April 22, 2016.

18. Goniewicz ML, Kuma T, Gawron M, et al. Nicotine levels in electronic cigarettes. Nicotine Tob Res. 2013;15:158-166.

19. Varlet V, Farsalinos K, Augsburger M, et al. Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health. 2015;12:4796-4815.

20. 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:e0116732.

21. Schober W, Szendrei K, Matzen W, et al. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health. 2014;217:628-637.

22. Schripp T, Markewitz D, Uhde E, et al. Does e-cigarette consumption cause passive vaping? Indoor Air. 2013;23:25-31.

23. The American Association of Poison Control Centers. E-cigarettes and liquid nicotine. Available at: http://www.aapcc.org/alerts/e-cigarettes/. Accessed May 12, 2016.

24. Krause MJ, Townsend TG. Hazardous waste status of discarded electronic cigarettes. Waste Manag. 2015;39:57-62.

25. U.S. Fire Administration. Electronic cigarette fires and explosions. October 2014. Available at: https://www.usfa.fema.gov/downloads/pdf/publications/electronic_cigarettes.pdf. Accessed May 17, 2016.

26. Skerfving S, Löfmark L, Lundh T, et al. Late effects of low blood lead concentrations in children on school performance and cognitive functions. Neurotoxicology. 2015;49:114-120.

27. Bernhoft RA. Cadmium toxicity and treatment. Scientific World Journal. 2013;394652.

28. Agency for Toxic Substances and Disease Registry. Case studies in environmental medicine (CSEM) Cadmium Toxicity. Available at: http://www.atsdr.cdc.gov/csem/cadmium/docs/cadmium.pdf. Accessed April 22, 2016.

29. Das KK, Buchner V. Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health. 2007;22:157-173.

30. England LJ, Bunnell RE, Pechacek TF, et al. Nicotine and the developing human: a neglected element in the electronic cigarette debate. Am J Prev Med. 2015;49:286-293.

31. Suter MA, Mastrobattista J, Sachs M, et al. Is there evidence for potential harm of electronic cigarette use in pregnancy? Birth defects research. Birth Defects Res A Clin Mol Teratol. 2015;103:186-195.

32. U.S. Preventive Services Task Force. Draft Recommendation Statement. Tobacco smoking cessation in adults and pregnant women: behavioral and pharmacotherapy interventions. Available at: http://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement147/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions1. Accessed March 22, 2016.

33. Peters EN, Harrell PT, Hendricks PS, et al. Electronic cigarettes in adults in outpatient substance use treatment: awareness, perceptions, use, and reasons for use. Am J Addict. 2015;24:233-239.

34. Kandel ER, Kandel DB. A molecular basis for nicotine as a gateway drug. N Engl J Med. 2014;371:932-943.

35. King BA, Patel R, Nguyen KH, et al. Trends in awareness and use of electronic cigarettes among US Adults, 2010-2013. Nicotine Tob Res. 2015;17:219-227.

36. McMillen RC, Gottlieb MA, Shaefer RM, et al. Trends in electronic cigarette use among U.S. adults: use is increasing in both smokers and nonsmokers. Nicotine Tob Res. 2015;1195-1202.

37. Lee S, Grana RA, Glantz SA. Electronic cigarette use among Korean adolescents: a cross-sectional study of market penetration, dual use, and relationship to quit attempts and former smoking. J Adolesc Health. 2014;54:684-690.

38. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382:1629-1637.

39. Nelson VA, Goniewicz ML, Beard E, et al. Comparison of the characteristics of long-term users of electronic cigarettes versus nicotine replacement therapy: a cross-sectional survey of English ex-smokers and current smokers. Drug Alcohol Depend. 2015;153:300-305.

40. Caponnetto P, Campagna D, Cibella F, et al. Efficiency and safety of an electronic cigarette (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013;8:e66317.

41. Polosa R, Caponnetto P, Morjaria JB, et al. Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health. 2011;11:786.

42. Malas M, van der Tempel J, Schwartz R, et al. Electronic cigarettes for smoking cessation: a systematic review. Nicotine Tob Res. 2016. [Epub ahead of print].

43. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110:1160-1168.

44. Bjartveit K, Tverdal A. Health consequences of smoking 1-4 cigarettes per day. Tob Control. 2005;14:315-320.

References

1. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129:1972-1986.

2. Vickerman KA, Carpenter KM, Altman T, et al. Use of electronic cigarettes among state tobacco cessation quitline callers. Nicotine Tob Res. 2013;15:1787-1791.

3. Grana R, Popova L, Ling P. A longitudinal analysis of electronic cigarette use and smoking cessation. JAMA Int Med. 2014;174:812-813.

4. U.S. Food and Drug Administration. Vaporizers, e-cigarettes, and other electronic nicotine delivery systems (ENDS). Available at: http://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm456610.htm. Accessed May 12, 2016.

5. Grana R, Benowitz N, Glantz SA. Background paper on E-cigarettes (electronic nicotine delivery systems). Center for Tobacco Control Research and Education, University of California, San Francisco, a WHO Collaborating Center on Tobacco Control. Prepared for World Health Organization Tobacco Free Initiative. December 2013. Available at: http://pvw.escholarship.org/uc/item/13p2b72n. Accessed March 31, 2014.

6. Zhu SH, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control. 2014;23:iii3-iii9.

7. Electronic Cigarette Use Among Adults: United States, 2014. NCHStats: A blog of the National Center for Health Statistics. Available at: http://nchstats.com/2015/10/28/electronic-cigarette-use-among-adults-united-states-2014/. Accessed April 22, 2016.

8. Centers for Disease Control and Prevention. E-cigarette use more than doubles among U.S. middle and high school students from 2011-2012. Available at: http://www.cdc.gov/media/releases/2013/p0905-ecigarette-use.html. Accessed April 22, 2016.

9. Centers for Disease Control and Prevention. Notes from the field: electronic cigarette use among middle and high school students — United States, 2011-2012. MMWR Morb Mortal Wkly Rep. 2013;62:729-730.

10. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students—United States, 2011-2015. MMWR Morb Mortal Wkly Rpt. 2016;65:361-367.

11. Kandra KL, Ranney LM, Lee JG, et al. Physicians’ attitudes and use of e-cigarettes as cessation devices, North Carolina, 2013. PloS One. 2014;9:e103462.

12. Schraufnagel DE. Electronic cigarettes: vulnerability of youth. Pediatr Allergy Immunol Pulmonol. 2015;28:2-6.

13. White J, Li J, Newcombe R, et al. Tripling use of electronic cigarettes among New Zealand adolescents between 2012 and 2014. J Adolesc Health. 2015;56:522-528.

14. Duke JC, Lee YO, Kim AE, et al. Exposure to electronic cigarette television advertisements among youth and young adults. Pediatrics. 2014;134:29-36.

15. Huang J, Kornfield R, Szczypka G, et al. A cross-sectional examination of marketing of electronic cigarettes on Twitter. Tob Control. 2014;23:iii26-iii30.

16. Rojewski AM, Coleman N, Toll BA. Position Statement: Emerging policy issues regarding electronic nicotine delivery systems: a need for regulation. Society of Behavioral Medicine. 2016. Available at: http://www.sbm.org/UserFiles/file/e-cig-statement_v2_lores.pdf. Accessed April 22, 2016.

17. McNeill A, Brose LS, Calder R, et al. E-cigarettes: an evidence update. A report commissioned by Public Health England. 2015. Available at: https://www.gov.uk/government/publications/e-cigarettes-an-evidence-update. Accessed April 22, 2016.

18. Goniewicz ML, Kuma T, Gawron M, et al. Nicotine levels in electronic cigarettes. Nicotine Tob Res. 2013;15:158-166.

19. Varlet V, Farsalinos K, Augsburger M, et al. Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health. 2015;12:4796-4815.

20. 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:e0116732.

21. Schober W, Szendrei K, Matzen W, et al. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health. 2014;217:628-637.

22. Schripp T, Markewitz D, Uhde E, et al. Does e-cigarette consumption cause passive vaping? Indoor Air. 2013;23:25-31.

23. The American Association of Poison Control Centers. E-cigarettes and liquid nicotine. Available at: http://www.aapcc.org/alerts/e-cigarettes/. Accessed May 12, 2016.

24. Krause MJ, Townsend TG. Hazardous waste status of discarded electronic cigarettes. Waste Manag. 2015;39:57-62.

25. U.S. Fire Administration. Electronic cigarette fires and explosions. October 2014. Available at: https://www.usfa.fema.gov/downloads/pdf/publications/electronic_cigarettes.pdf. Accessed May 17, 2016.

26. Skerfving S, Löfmark L, Lundh T, et al. Late effects of low blood lead concentrations in children on school performance and cognitive functions. Neurotoxicology. 2015;49:114-120.

27. Bernhoft RA. Cadmium toxicity and treatment. Scientific World Journal. 2013;394652.

28. Agency for Toxic Substances and Disease Registry. Case studies in environmental medicine (CSEM) Cadmium Toxicity. Available at: http://www.atsdr.cdc.gov/csem/cadmium/docs/cadmium.pdf. Accessed April 22, 2016.

29. Das KK, Buchner V. Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health. 2007;22:157-173.

30. England LJ, Bunnell RE, Pechacek TF, et al. Nicotine and the developing human: a neglected element in the electronic cigarette debate. Am J Prev Med. 2015;49:286-293.

31. Suter MA, Mastrobattista J, Sachs M, et al. Is there evidence for potential harm of electronic cigarette use in pregnancy? Birth defects research. Birth Defects Res A Clin Mol Teratol. 2015;103:186-195.

32. U.S. Preventive Services Task Force. Draft Recommendation Statement. Tobacco smoking cessation in adults and pregnant women: behavioral and pharmacotherapy interventions. Available at: http://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement147/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions1. Accessed March 22, 2016.

33. Peters EN, Harrell PT, Hendricks PS, et al. Electronic cigarettes in adults in outpatient substance use treatment: awareness, perceptions, use, and reasons for use. Am J Addict. 2015;24:233-239.

34. Kandel ER, Kandel DB. A molecular basis for nicotine as a gateway drug. N Engl J Med. 2014;371:932-943.

35. King BA, Patel R, Nguyen KH, et al. Trends in awareness and use of electronic cigarettes among US Adults, 2010-2013. Nicotine Tob Res. 2015;17:219-227.

36. McMillen RC, Gottlieb MA, Shaefer RM, et al. Trends in electronic cigarette use among U.S. adults: use is increasing in both smokers and nonsmokers. Nicotine Tob Res. 2015;1195-1202.

37. Lee S, Grana RA, Glantz SA. Electronic cigarette use among Korean adolescents: a cross-sectional study of market penetration, dual use, and relationship to quit attempts and former smoking. J Adolesc Health. 2014;54:684-690.

38. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382:1629-1637.

39. Nelson VA, Goniewicz ML, Beard E, et al. Comparison of the characteristics of long-term users of electronic cigarettes versus nicotine replacement therapy: a cross-sectional survey of English ex-smokers and current smokers. Drug Alcohol Depend. 2015;153:300-305.

40. Caponnetto P, Campagna D, Cibella F, et al. Efficiency and safety of an electronic cigarette (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013;8:e66317.

41. Polosa R, Caponnetto P, Morjaria JB, et al. Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health. 2011;11:786.

42. Malas M, van der Tempel J, Schwartz R, et al. Electronic cigarettes for smoking cessation: a systematic review. Nicotine Tob Res. 2016. [Epub ahead of print].

43. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110:1160-1168.

44. Bjartveit K, Tverdal A. Health consequences of smoking 1-4 cigarettes per day. Tob Control. 2005;14:315-320.

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Offer these interventions to help prevent suicide by firearm

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Offer these interventions to help prevent suicide by firearm

Firearms are the most common means of suicide in the United States, accounting for approximately 20,000 adult deaths annually,1 which is approximately two-thirds of the more than 32,000 gun-related fatalities each year in the United States. Of approximately 3,000 American children who are shot to death annually, one-third are suicides.1-4

Firearms are dangerous; it has been documented that even guns obtained for recreation or protection increase the risk of suicide, homicide, or injury.2,3 This problem has become a public health concern.3-8 Because most suicide attempts with firearms are fatal, psychiatrists have an interest in reducing such outcomes.1-8


Risk factors for suicide by firearm

Easy availability of a gun in the home, with ammunition present—especially a gun that is kept loaded and not locked up—is the one of the biggest risk factors for suicide by firearms.4 Unrestricted, quick access allows people who are impulsive little time to reconsider suicide. The risk presented by easy availability is magnified by dangerous concomitant intoxication (see below), distress, and lack of supervision (of children).

Alcohol consumption is associated with suicide. Approximately one-fourth of the people who commit suicide are intoxicated at the time of death.9 Alcohol use, especially binge drinking, is observed in an even larger percentage of suicide attempts than individuals using guns while sober.

Female sex. In recent years, gun use by women has increased, along with firearm-related suicide. Simply having a gun at home greatly increases the suicide rate for women.2-4

People with a history of high impulsivity, impaired judgment, violence, or psychiatric and neurologic disorders places people at greater risk of shooting themselves, especially those with depression, suicidal ideation, substance abuse, psychosis, or dementia.4

Older age, particularly men who live alone, increases the risk of suicide by firearms, especially in the context of chronic pain or other health problems. Gunfire is the most common means of suicide among geriatric patients of both sexes.8

Lethality. In general, suicide attempts with guns are more likely to be fatal than overdosing, poisoning, or self-mutilation.1,2 Most self-inflicted gunshot wounds result in death, usually on the day of the shooting.1,2

Evidence about these risk factors has led the American Medical Association and other health care groups to encourage physicians—in particular, psychiatric clinicians who focus on suicide prevention—to counsel patients about gun safety.


What can you do to minimize risk?
Gun-related inquiry and counsel by psychiatrists can benefit patients and their family.4 Be aware, however, of restrictions on such discussions by health care providers in some states (Box).10


Ask about the presence of firearms in the home.
Our advice and our “doctor’s orders” are a means to promote health; suggestions in the context of a supportive physician-patient relationship could result in compliance.3,4 Firearm-focused discussions might be uncomfortable or unpopular but are critical for preventing suicide. Openly discussing such issues with our patients could avoid tragedies.4 Involving family or significant others in these interventions also might be helpful.

Ask about access to and storage of firearms.
Simply talking about gun safety is helpful.4 Seeking information about gun usage is especially called for in psychiatric practices that treat patients with suicidal ideation, depression, substance abuse, and cognitive impairment.8 Discuss firearm availability with patients who have a history of substance use, impulsivity, anger, or violence, or who have a brain disorder or neurologic condition. Talking about firearms with patients and educating them about safety is indicated whenever you observe a risk factor for suicide.

Advise safe storage. Aim to have the entire family agree to a safety policy. Guns should be kept unloaded and not stored with ammunition (eg, keep guns in the attic and ammunition in the basement), which might diminish the risk of (1) an impulsive shooting and (2) a planned attempt by giving people time to consider options other than suicide. Firearm safety includes locking ammunition and weapons in a safe and applying trigger locks. Try to get patients and their family to plan for compliance with such recommendations whenever possible.

Guide dialogue and educate patients about handling guns safely. Be sure that patients know that most firearm deaths that happen inside a home are suicide.2-4 Advise patients, and their family, that firearms should not be handled while intoxicated.4 Encourage families to remove gun access from members who are suicidal, depressed, abusing pharmaceuticals or using illicit drugs, and those in distress or with a significant mental or neurologic illness.

In such circumstances, institute a protective plan to prevent shootings. This can be time-limited, or might include removing guns or ammunition from the home or deactivating firing mechanisms, etc. For safety reasons, some families do not keep ammunition in their home.

 

 

Additionally, firearms in the hands of children ought to include close monitoring by a responsible, sober adult. Keeping guns in locked storage is especially important for preventing suicide in children. Despite suicide being less frequent among younger people than in adults, taking steps to avoid 1,000 child suicides each year in the United States is a valuable intervention.


Conclusion

Specific inquiry, overt discussion, and face-to-face counseling about gun safety can be a life-saving aspect of psychiatric intervention. With such recommendations and education, psychiatrists can play a productive role in reducing firearm-related suicide.


Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
References


1. Center for Disease Control and Prevention. Injury prevention and control: data and statistics. http://www.cdc.gov/injury/wisqars. Updated December 8, 2015. Accessed April 1, 2016.
2. Narang P, Paladugu A, Manda SR, et al. Do guns provide safety? At what cost? South Med J. 2010;103(2):151-153.
3. Cherlopalle S, Kolikonda MK, Enja M, et al. Guns in America: defense or danger? J Trauma Treat. 2014;3(4):207.
4. Lippmann S. Doctors teaching gun safety. Journal of the Kentucky Medical Association. 2015;113(4):112.
5. Cooke BK, Goddard ER, Ginory A, et al. Firearms inquiries in Florida: “medical privacy” or medical neglect? J Am Acad Psychiatry Law. 2012;40(3):399-408.
6. Valeras AB. Patient with gun. Fam Med. 2013;45(8):584-585.
7. Butkus R, Weissman A. Internists’ attitude toward prevention of firearm injury. Ann Intern Med. 2015;160(12):821-827.
8. Kapp MB. Geriatric patients, firearms, and physicians. Ann Intern Med. 2013;159(6):421-422.
9. Kaplan MS, McFarland BH, Huguet N, et al. Acute alcohol intoxication and suicide: a gender-stratified analysis of the National Violent Death Reporting System. Inj Prev. 2013;19(1):38-43.
10. Fla Stat §790.338.

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Steven Lippmann, MD
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Firearms are the most common means of suicide in the United States, accounting for approximately 20,000 adult deaths annually,1 which is approximately two-thirds of the more than 32,000 gun-related fatalities each year in the United States. Of approximately 3,000 American children who are shot to death annually, one-third are suicides.1-4

Firearms are dangerous; it has been documented that even guns obtained for recreation or protection increase the risk of suicide, homicide, or injury.2,3 This problem has become a public health concern.3-8 Because most suicide attempts with firearms are fatal, psychiatrists have an interest in reducing such outcomes.1-8


Risk factors for suicide by firearm

Easy availability of a gun in the home, with ammunition present—especially a gun that is kept loaded and not locked up—is the one of the biggest risk factors for suicide by firearms.4 Unrestricted, quick access allows people who are impulsive little time to reconsider suicide. The risk presented by easy availability is magnified by dangerous concomitant intoxication (see below), distress, and lack of supervision (of children).

Alcohol consumption is associated with suicide. Approximately one-fourth of the people who commit suicide are intoxicated at the time of death.9 Alcohol use, especially binge drinking, is observed in an even larger percentage of suicide attempts than individuals using guns while sober.

Female sex. In recent years, gun use by women has increased, along with firearm-related suicide. Simply having a gun at home greatly increases the suicide rate for women.2-4

People with a history of high impulsivity, impaired judgment, violence, or psychiatric and neurologic disorders places people at greater risk of shooting themselves, especially those with depression, suicidal ideation, substance abuse, psychosis, or dementia.4

Older age, particularly men who live alone, increases the risk of suicide by firearms, especially in the context of chronic pain or other health problems. Gunfire is the most common means of suicide among geriatric patients of both sexes.8

Lethality. In general, suicide attempts with guns are more likely to be fatal than overdosing, poisoning, or self-mutilation.1,2 Most self-inflicted gunshot wounds result in death, usually on the day of the shooting.1,2

Evidence about these risk factors has led the American Medical Association and other health care groups to encourage physicians—in particular, psychiatric clinicians who focus on suicide prevention—to counsel patients about gun safety.


What can you do to minimize risk?
Gun-related inquiry and counsel by psychiatrists can benefit patients and their family.4 Be aware, however, of restrictions on such discussions by health care providers in some states (Box).10


Ask about the presence of firearms in the home.
Our advice and our “doctor’s orders” are a means to promote health; suggestions in the context of a supportive physician-patient relationship could result in compliance.3,4 Firearm-focused discussions might be uncomfortable or unpopular but are critical for preventing suicide. Openly discussing such issues with our patients could avoid tragedies.4 Involving family or significant others in these interventions also might be helpful.

Ask about access to and storage of firearms.
Simply talking about gun safety is helpful.4 Seeking information about gun usage is especially called for in psychiatric practices that treat patients with suicidal ideation, depression, substance abuse, and cognitive impairment.8 Discuss firearm availability with patients who have a history of substance use, impulsivity, anger, or violence, or who have a brain disorder or neurologic condition. Talking about firearms with patients and educating them about safety is indicated whenever you observe a risk factor for suicide.

Advise safe storage. Aim to have the entire family agree to a safety policy. Guns should be kept unloaded and not stored with ammunition (eg, keep guns in the attic and ammunition in the basement), which might diminish the risk of (1) an impulsive shooting and (2) a planned attempt by giving people time to consider options other than suicide. Firearm safety includes locking ammunition and weapons in a safe and applying trigger locks. Try to get patients and their family to plan for compliance with such recommendations whenever possible.

Guide dialogue and educate patients about handling guns safely. Be sure that patients know that most firearm deaths that happen inside a home are suicide.2-4 Advise patients, and their family, that firearms should not be handled while intoxicated.4 Encourage families to remove gun access from members who are suicidal, depressed, abusing pharmaceuticals or using illicit drugs, and those in distress or with a significant mental or neurologic illness.

In such circumstances, institute a protective plan to prevent shootings. This can be time-limited, or might include removing guns or ammunition from the home or deactivating firing mechanisms, etc. For safety reasons, some families do not keep ammunition in their home.

 

 

Additionally, firearms in the hands of children ought to include close monitoring by a responsible, sober adult. Keeping guns in locked storage is especially important for preventing suicide in children. Despite suicide being less frequent among younger people than in adults, taking steps to avoid 1,000 child suicides each year in the United States is a valuable intervention.


Conclusion

Specific inquiry, overt discussion, and face-to-face counseling about gun safety can be a life-saving aspect of psychiatric intervention. With such recommendations and education, psychiatrists can play a productive role in reducing firearm-related suicide.


Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Firearms are the most common means of suicide in the United States, accounting for approximately 20,000 adult deaths annually,1 which is approximately two-thirds of the more than 32,000 gun-related fatalities each year in the United States. Of approximately 3,000 American children who are shot to death annually, one-third are suicides.1-4

Firearms are dangerous; it has been documented that even guns obtained for recreation or protection increase the risk of suicide, homicide, or injury.2,3 This problem has become a public health concern.3-8 Because most suicide attempts with firearms are fatal, psychiatrists have an interest in reducing such outcomes.1-8


Risk factors for suicide by firearm

Easy availability of a gun in the home, with ammunition present—especially a gun that is kept loaded and not locked up—is the one of the biggest risk factors for suicide by firearms.4 Unrestricted, quick access allows people who are impulsive little time to reconsider suicide. The risk presented by easy availability is magnified by dangerous concomitant intoxication (see below), distress, and lack of supervision (of children).

Alcohol consumption is associated with suicide. Approximately one-fourth of the people who commit suicide are intoxicated at the time of death.9 Alcohol use, especially binge drinking, is observed in an even larger percentage of suicide attempts than individuals using guns while sober.

Female sex. In recent years, gun use by women has increased, along with firearm-related suicide. Simply having a gun at home greatly increases the suicide rate for women.2-4

People with a history of high impulsivity, impaired judgment, violence, or psychiatric and neurologic disorders places people at greater risk of shooting themselves, especially those with depression, suicidal ideation, substance abuse, psychosis, or dementia.4

Older age, particularly men who live alone, increases the risk of suicide by firearms, especially in the context of chronic pain or other health problems. Gunfire is the most common means of suicide among geriatric patients of both sexes.8

Lethality. In general, suicide attempts with guns are more likely to be fatal than overdosing, poisoning, or self-mutilation.1,2 Most self-inflicted gunshot wounds result in death, usually on the day of the shooting.1,2

Evidence about these risk factors has led the American Medical Association and other health care groups to encourage physicians—in particular, psychiatric clinicians who focus on suicide prevention—to counsel patients about gun safety.


What can you do to minimize risk?
Gun-related inquiry and counsel by psychiatrists can benefit patients and their family.4 Be aware, however, of restrictions on such discussions by health care providers in some states (Box).10


Ask about the presence of firearms in the home.
Our advice and our “doctor’s orders” are a means to promote health; suggestions in the context of a supportive physician-patient relationship could result in compliance.3,4 Firearm-focused discussions might be uncomfortable or unpopular but are critical for preventing suicide. Openly discussing such issues with our patients could avoid tragedies.4 Involving family or significant others in these interventions also might be helpful.

Ask about access to and storage of firearms.
Simply talking about gun safety is helpful.4 Seeking information about gun usage is especially called for in psychiatric practices that treat patients with suicidal ideation, depression, substance abuse, and cognitive impairment.8 Discuss firearm availability with patients who have a history of substance use, impulsivity, anger, or violence, or who have a brain disorder or neurologic condition. Talking about firearms with patients and educating them about safety is indicated whenever you observe a risk factor for suicide.

Advise safe storage. Aim to have the entire family agree to a safety policy. Guns should be kept unloaded and not stored with ammunition (eg, keep guns in the attic and ammunition in the basement), which might diminish the risk of (1) an impulsive shooting and (2) a planned attempt by giving people time to consider options other than suicide. Firearm safety includes locking ammunition and weapons in a safe and applying trigger locks. Try to get patients and their family to plan for compliance with such recommendations whenever possible.

Guide dialogue and educate patients about handling guns safely. Be sure that patients know that most firearm deaths that happen inside a home are suicide.2-4 Advise patients, and their family, that firearms should not be handled while intoxicated.4 Encourage families to remove gun access from members who are suicidal, depressed, abusing pharmaceuticals or using illicit drugs, and those in distress or with a significant mental or neurologic illness.

In such circumstances, institute a protective plan to prevent shootings. This can be time-limited, or might include removing guns or ammunition from the home or deactivating firing mechanisms, etc. For safety reasons, some families do not keep ammunition in their home.

 

 

Additionally, firearms in the hands of children ought to include close monitoring by a responsible, sober adult. Keeping guns in locked storage is especially important for preventing suicide in children. Despite suicide being less frequent among younger people than in adults, taking steps to avoid 1,000 child suicides each year in the United States is a valuable intervention.


Conclusion

Specific inquiry, overt discussion, and face-to-face counseling about gun safety can be a life-saving aspect of psychiatric intervention. With such recommendations and education, psychiatrists can play a productive role in reducing firearm-related suicide.


Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
References


1. Center for Disease Control and Prevention. Injury prevention and control: data and statistics. http://www.cdc.gov/injury/wisqars. Updated December 8, 2015. Accessed April 1, 2016.
2. Narang P, Paladugu A, Manda SR, et al. Do guns provide safety? At what cost? South Med J. 2010;103(2):151-153.
3. Cherlopalle S, Kolikonda MK, Enja M, et al. Guns in America: defense or danger? J Trauma Treat. 2014;3(4):207.
4. Lippmann S. Doctors teaching gun safety. Journal of the Kentucky Medical Association. 2015;113(4):112.
5. Cooke BK, Goddard ER, Ginory A, et al. Firearms inquiries in Florida: “medical privacy” or medical neglect? J Am Acad Psychiatry Law. 2012;40(3):399-408.
6. Valeras AB. Patient with gun. Fam Med. 2013;45(8):584-585.
7. Butkus R, Weissman A. Internists’ attitude toward prevention of firearm injury. Ann Intern Med. 2015;160(12):821-827.
8. Kapp MB. Geriatric patients, firearms, and physicians. Ann Intern Med. 2013;159(6):421-422.
9. Kaplan MS, McFarland BH, Huguet N, et al. Acute alcohol intoxication and suicide: a gender-stratified analysis of the National Violent Death Reporting System. Inj Prev. 2013;19(1):38-43.
10. Fla Stat §790.338.

References


1. Center for Disease Control and Prevention. Injury prevention and control: data and statistics. http://www.cdc.gov/injury/wisqars. Updated December 8, 2015. Accessed April 1, 2016.
2. Narang P, Paladugu A, Manda SR, et al. Do guns provide safety? At what cost? South Med J. 2010;103(2):151-153.
3. Cherlopalle S, Kolikonda MK, Enja M, et al. Guns in America: defense or danger? J Trauma Treat. 2014;3(4):207.
4. Lippmann S. Doctors teaching gun safety. Journal of the Kentucky Medical Association. 2015;113(4):112.
5. Cooke BK, Goddard ER, Ginory A, et al. Firearms inquiries in Florida: “medical privacy” or medical neglect? J Am Acad Psychiatry Law. 2012;40(3):399-408.
6. Valeras AB. Patient with gun. Fam Med. 2013;45(8):584-585.
7. Butkus R, Weissman A. Internists’ attitude toward prevention of firearm injury. Ann Intern Med. 2015;160(12):821-827.
8. Kapp MB. Geriatric patients, firearms, and physicians. Ann Intern Med. 2013;159(6):421-422.
9. Kaplan MS, McFarland BH, Huguet N, et al. Acute alcohol intoxication and suicide: a gender-stratified analysis of the National Violent Death Reporting System. Inj Prev. 2013;19(1):38-43.
10. Fla Stat §790.338.

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Have we done enough to educate patients about e-cigarettes?

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Have we done enough to educate patients about e-cigarettes?

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.1 They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia2), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.3 A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.3 Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.1 Lead causes severe neurotoxicity,4 cadmium can cause organ damage,5 and inhaled nickel causes an inflammatory reaction in the lungs.6

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD

Louisville, Ky

References

1. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129:1972-1986.

2. Bjartveit K, Tverdal A. Health consequences of smoking 1-4 cigarettes per day. Tob Control. 2005;14:315-320.

3. Varlet V, Farsalinos K, Augsburger M, et al. Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health. 2015;12:4796-4815.

4. Skerfving S, Löfmark L, Lundh T, et al. Late effects of low blood lead concentrations in children on school performance and cognitive functions. Neurotoxicology. 2015;49:114-120.

5. Bernhoft RA. Cadmium toxicity and treatment. Scientific-World-Journal. 2013;2013:394652.

6. Das KK, Buchner V. Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health. 2007;22:157-173.

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Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.1 They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia2), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.3 A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.3 Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.1 Lead causes severe neurotoxicity,4 cadmium can cause organ damage,5 and inhaled nickel causes an inflammatory reaction in the lungs.6

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD

Louisville, Ky

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.1 They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia2), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.3 A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.3 Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.1 Lead causes severe neurotoxicity,4 cadmium can cause organ damage,5 and inhaled nickel causes an inflammatory reaction in the lungs.6

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD

Louisville, Ky

References

1. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129:1972-1986.

2. Bjartveit K, Tverdal A. Health consequences of smoking 1-4 cigarettes per day. Tob Control. 2005;14:315-320.

3. Varlet V, Farsalinos K, Augsburger M, et al. Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health. 2015;12:4796-4815.

4. Skerfving S, Löfmark L, Lundh T, et al. Late effects of low blood lead concentrations in children on school performance and cognitive functions. Neurotoxicology. 2015;49:114-120.

5. Bernhoft RA. Cadmium toxicity and treatment. Scientific-World-Journal. 2013;2013:394652.

6. Das KK, Buchner V. Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health. 2007;22:157-173.

References

1. Grana R, Benowitz N, Glantz SA. E-cigarettes: a scientific review. Circulation. 2014;129:1972-1986.

2. Bjartveit K, Tverdal A. Health consequences of smoking 1-4 cigarettes per day. Tob Control. 2005;14:315-320.

3. Varlet V, Farsalinos K, Augsburger M, et al. Toxicity assessment of refill liquids for electronic cigarettes. Int J Environ Res Public Health. 2015;12:4796-4815.

4. Skerfving S, Löfmark L, Lundh T, et al. Late effects of low blood lead concentrations in children on school performance and cognitive functions. Neurotoxicology. 2015;49:114-120.

5. Bernhoft RA. Cadmium toxicity and treatment. Scientific-World-Journal. 2013;2013:394652.

6. Das KK, Buchner V. Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health. 2007;22:157-173.

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