E-Cigarettes: What Do We Know Today and What Should We Tell Our Patients?

December 13, 2022

Written By: Luba Yammine, PhD

The prevalence of cigarette smoking in the U.S. has decreased substantially over the last several decades, from 42.6% in 1965 to 13.7% in 2018.1  While this reduction in cigarette smoking is encouraging, the tobacco product landscape has been evolving with the advent of new tobacco products, including electronic cigarettes (EC).

EC come in various shapes and sizes and are known by different names, such as e-cigs, mods, vape pens, or electronic nicotine delivery systems. Some EC look like conventional cigarettes or cigars, while others look like USB flash drives or pens. Most EC have a battery, a chamber to hold a liquid, and a heating element that facilitates the conversion of the liquid into an aerosol which users inhale into their lungs. Most EC liquids contain nicotine. The process of using EC is commonly known as vaping.

EC are especially popular among youth. From 2011 to 2019, the use of EC increased from 0.6% to 10.5% and from 1.5% to 27.5% among middle and high schoolers, respectively.2 EC use has been growing among the adults as well, increasing from 4.4% in 2017 to 5.5% in 2018. While there was a slight reduction t0 5.1% in 2020, the prevalence of daily EC use among the adults has grown from 1.5% in 2017, to 2.1% in 2018, to 2.3% in 2020.3

Various policies have been and continue to be implemented in the last few years to combat the use of EC among youth and young adults. In December 2019, the federal minimum age for the sale of all tobacco products, including EC, was raised from 18 to 21 years, making it illegal to persons younger than 21 years to purchase all tobacco products. Further, since most youth and young adults use flavored EC products, in February 2020, the FDA implemented a ban on flavored cartridge-based EC3 (significantly, the ban does not apply to disposable EC which come in a variety of flavors that appeal to youth). Some U.S. cities have implemented local policies to decrease EC use. For example, in 2019 San Francisco became the first U.S. city to completely ban the sale and distribution of EC.

Despite these measures, EC use remains high, especially among youth, which has been a cause of serious public health concerns. The literature and information in the media regarding EC are profuse and often contradictory, from claims that EC is a safe and effective smoking cessation tool to reports that EC may cause lung injury and other negative health outcomes.

Do EC help people quit smoking?

A 2022 Cochrane review4 of 78 studies, including 40 randomized controlled trials, sought to assess the effectiveness, tolerability, and safety of EC in helping people quit smoking. The review included studies that compared nicotine-containing EC to various smoking cessation modalities, such as nicotine replacement therapy (NRT), varenicline (Chantix), EC without nicotine, and behavioral support, as well as studies that compared nicotine-containing EC to no smoking cessation support. The results indicated that there was high-certainty evidence that nicotine-containing EC were more likely to help people quit smoking for at least 6 months than NRT, and there was moderate-certainty evidence that EC containing nicotine were more effective than EC without nicotine. Evidence comparing nicotine-containing EC with usual care/no treatment also suggested benefit, but this evidence was less certain. With regard to the unwanted effects of nicotine-containing EC, throat or mouth irritation, headache, and nausea were identified as most frequent. There was no evidence of serious harm; however, the authors acknowledged that the longest follow-up was two years, and the number of studies that included the two-year follow-up was small.

This review raised concerns in the scientific community.5,6 For example, the review was criticized for including uncontrolled intervention studies and for the lack of a balanced scientific view. Regarding the latter, there were criticisms that the authors of the review did not acknowledge that population-based cohort studies do not show a benefit of EC on smoking cessation; that many who use EC for smoking cessation continue using EC long-term and/or become “dual users” of both combustible cigarettes and EC; and that a large number of in-vitro, preclinical, clinical, and population-based studies have shown negative health effects of EC use.5,6

Notably, the aforementioned Cochrane review was updated in 20227 and included 19 studies. This time, the investigators aimed to examine the proportion of people still using EC, both with nicotine and without, at 6 months or longer. Findings indicated that of participants who quit combustible cigarettes, 70% were still using EC at 6 months or longer, with more people using nicotine EC than non-nicotine EC.

What do we know regarding the risks of EC?  

While EC are void of many toxic compounds found in combustible cigarettes, EC are not toxin free. For example, diacetyl, a flavor enhancer linked to bronchiolitis obliterans (‘popcorn lung’) and other severe respiratory diseases, has been identified in some vaping liquids, particularly those with flavorings.8 The presence of metals and metalloids (i.e. arsenic, chromium, lead, nickel) in EC is a major concern, given their serious health effects, including cancer. A systematic review of studies on metal/metalloid levels in biological samples (blood, urine, saliva) of EC users found that the levels of most metals/metalloids were similar or even higher in EC users compared to users of combustible cigarettes or cigars.9 Another concern is the use of propylene glycol and glycerol in vaping liquid – both are known airway irritants.

E-cigarette or vaping use-associated lung injury (EVALI) was initially recognized in the summer of 2019. The pathogenesis of EVALI is unknown at this time. The condition presents with flu-like symptoms which can often escalate into severe pneumonia and respiratory failure. Examination of products used by affected patients and biological samples found THC and/or vitamin E acetate in the majority. However, other additives may be involved including CBD oils, coconut oil, and other substances. EVALI appears to be isolated to the U.S., with only sporadic cases of EVALI reported in Europe (U.K.) and in individuals traveling from the U.S. to Europe.10 Of note, oil-based vaping products are banned in the U.K.

Recent studies evaluated the relationship between EC use and COVID-19. Findings showed an increased COVID-19 susceptibility and greater disease severity, including death, among EC users, similar to smokers of combustible cigarettes. The increased risk of COVID-related illness could be due to the EC-associated damage in the epithelial barrier which increases the permeability to inhaled pathogens and decreases clearance of secretions.11,12

A review published in 2019 found that over a 3-year period (2015-2017), 90 cases of EC related burn injuries were reported. The authors noted that this number is likely to be underestimated. Battery malfunction (overheating with subsequent explosion) is the suggested mechanism of EC related injuries, resulting in thermal and chemical burns, some of which requiring skin grafting.13

There is literature suggesting that among youth, EC may serve as a gateway to initiating the use of combustible cigarettes (and other substances). Indeed, there is evidence showing a strong association between  e-cigarette use and subsequent smoking of combustible cigarettes.14 The gateway hypothesis, is not, however, universally accepted by the scientific community, with the most common alternative hypothesis being the ‘common liability theory’, which emphasizes shared predisposing characteristics among multidrug users.15

While more research is needed to further elucidate the gateway effect of EC, addiction to nicotine among youth is a major public health concern. As noted above, most EC liquids contain nicotine, the principal addictive substance compound found in combustible cigarettes and other tobacco products. In the brain, nicotine attaches to the nicotinic acetylcholine receptors, which promotes the release of various neurotransmitters, including dopamine, which causes the feelings of pleasure, upregulates acetylcholine receptors, and alters brain circuitry involved in learning, stress, and self-control, resulting in addiction and dependence. Adolescents and young adults are especially susceptible to nicotine receptor upregulation and addiction.2

Importantly, nicotine concentration in vaping liquids can vary substantially based on the manufacturer, and concentration is dependent on the types of ingredients in the liquids. This concentration can be quite high and cause toxicity. The more recent EC products, referred to as fourth-generation EC, frequently use nicotine salts. Nicotine salts have a lower pH and are less irritating; however, nicotine salts are associated with higher nicotine concentration and more efficient nicotine delivery.16

It is worth noting that it took decades of longitudinal cohort studies to establish that cigarette smoking causes lung cancer and other negative health outcomes.17 With EC being relatively new to the market, the jury is still out as to the potential long-term consequences of EC, and it may take years before these downstream effects of EC are fully recognized. To further complicate this issue, some EC users are former cigarette smokers, making it difficult to separate the impact of smoking combustible cigarettes from the effects of EC.

What are the current recommendations regarding EC use and what should we tell our patients?

  • Patients should be assessed regarding use of all tobacco products, including alternative products, such as EC.
  • EC are not an approved smoking cessation treatment in the U.S. However, there is accumulating evidence suggesting that EC could be used as a form of harm reduction in long-term adult cigarette smokers who have failed first line smoking cessation treatments. Patients who use EC as an alternative to combustible cigarettes should be advised to completely switch from combustible cigarettes to EC and avoid dual use that delays quitting smoking completely. Smoking cessation counseling should still be recommended for persons who use EC as a harm reduction strategy.
  • EC use among youth, young adults, pregnant women, and adults who do not currently use tobacco products should be strongly discouraged.
  • EC should not be referred to as harmless. It is essential that clinicians address the known risks of EC and advise patients that there are likely harms from EC use that are still unknown.
  • Clinicians should stay up to date with the most recent scientific evidence related to the potential benefits and harms of EC and provide patients with the most current and accurate information as new data become available.

 

References:

  1. Smoking Cessation: a Report of the Surgeon General 2020. at https://www.cdc.gov/tobacco/data_statistics/sgr/2020-smoking-cessation/?s_cid=OSH_misc_m180.)
  2. Glantz S, Jeffers A, Winickoff JP. Nicotine Addiction and Intensity of e-Cigarette Use by Adolescents in the US, 2014 to 2021. JAMA Network Open 2022;5:e2240671-e.
  3. Boakye E, Osuji N, Erhabor J, et al. Assessment of Patterns in e-Cigarette Use Among Adults in the US, 2017-2020. JAMA Netw Open 2022;5:e2223266.
  4. Hartmann-Boyce J, McRobbie H, Butler AR, et al. Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews 2021.
  5. Pisinger C, Vestbo J. A new Cochrane review on electronic cigarettes for smoking cessation: should we change our practice? Eur Respir J 2020;56.
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  7. Butler AR, Lindson N, Fanshawe TR, et al. Longer-term use of electronic cigarettes when provided as a stop smoking aid: Systematic review with meta-analyses. Preventive medicine 2022:107182.
  8. Allen JG, Flanigan SS, LeBlanc M, et al. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect 2016;124:733-9.
  9. Zhao D, Aravindakshan A, Hilpert M, et al. Metal/Metalloid Levels in Electronic Cigarette Liquids, Aerosols, and Human Biosamples: A Systematic Review. Environ Health Perspect 2020;128:36001.
  10. Schier JG, Meiman JG, Layden J, et al. Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use – Interim Guidance. MMWR Morbidity and mortality weekly report 2019;68:787-90.
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  12. Poudel R, Daniels LB, DeFilippis AP, et al. Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections. PloS one 2022;17:e0270763.
  13. Jones CD, Ho W, Gunn E, Widdowson D, Bahia H. E-cigarette burn injuries: Comprehensive review and management guidelines proposal. Burns 2019;45:763-71.
  14. Khouja JN, Suddell SF, Peters SE, Taylor AE, Munafò MR. Is e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis. Tobacco Control 2021;30:8-15.
  15. Chapman S, Bareham D, Maziak W. The Gateway Effect of E-cigarettes: Reflections on Main Criticisms. Nicotine Tob Res 2019;21:695-8.
  16. Benowitz NL, St Helen G, Liakoni E. Clinical Pharmacology of Electronic Nicotine Delivery Systems (ENDS): Implications for Benefits and Risks in the Promotion of the Combusted Tobacco Endgame. J Clin Pharmacol 2021;61 Suppl 2:S18-s36.
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