E-cigarettes for tobacco cessation: Not the solution.

Abstract

NPs practicing in primary care frequently encounter patients who use electronic nicotine delivery systems (ENDS), some for the purpose of tobacco cessation. Research shows that clinician involvement in tobacco cessation increases the likelihood of success, and the desire to quit appears to be the strongest predictive factor for successful cessation.1,2 Patients seeking evidence-based assistance regarding tobacco cessation, such as nicotine replacement or cessation medication, are two to three times more likely to quit than those who do not.3 Despite the common belief that ENDS products, which include e-cigarettes, tank systems, and other vaping devices, are suitable for tobacco cessation, they are not recommended for this purpose because of health risks and lack of FDA approval, among other reasons. NPs can positively impact their patients' ability to achieve cessation from smoking and other tobacco products without the use of ENDS, and many resources are available to aid them in this process. It has been known since at least 1988 that nicotine is the addictive substance in tobacco.4 Nicotine reaches the brain within seconds of taking a puff and increases the release of neurotransmitters, including dopamine, that regulate mood and behavior.5 Dopamine is released in the reward center of the brain, resulting in improved mood and pleasant feelings. Over time, neuronal changes occur; thus, nicotine addiction is a chronic neurologic disorder frequently requiring treatment to overcome.6 When ENDS were introduced, it was speculated that the devices could be a powerful tool for tobacco cessation by providing a safer alternative to cigarettes, with the allure of a smoking-like behavior replacement. The liquid used with ENDS, sometimes referred to as e-liquid, produces a harmful aerosol when heated that is inhaled by users and involuntarily inhaled by nonusers.3,7,8 E-liquids usually contain nicotine, and more than half of the people who start using ENDS for tobacco cessation transfer their nicotine dependence to ENDS, often becoming dual users.3,9,10 ENDS use among adolescents is associated with increased initiation of cigarette smoking and increased frequency and intensity of both regular cigarette and e-cigarette usage.11 ENDS product use among adolescents leads to increased dependence on nicotine products.10 After years of market availability, three separate clinical guidelines recommend against the use of ENDs for tobacco cessation because of quality control concerns, insufficient data to demonstrate that the benefits outweigh the risks, and the availability of effective cessation tools. This article examines why ENDS products are not an effective, safe, or approved means of cessation for either adults or adolescents. ENDS products Youth cigarette usage has been steadily declining in recent years, but tobacco use rates remain stubbornly fixed at approximately 20% because noncigarette forms of tobacco, primarily ENDs, are increasingly used by adolescents and young adults.12 In 2020, 19.6% of high-school students in the US reported using ENDS, along with 4.7% of middle-school students.12,13 With 8.2% and 2.8% of high-school and middle-school students, respectively, reporting use of multiple tobacco products, it is clear that many youth are becoming addicted to nicotine by starting with ENDS use alone.13 Nonetheless, polytobacco use (using more than one tobacco product) is increasingly common as the market popularity of ENDS products has increased. Polytobacco users are more likely to report dependence, elucidated as early-morning cravings.12 Notably, attempts to quit among polytobacco users have been higher than cigarette-only users, suggesting that e-cigarette users are employing e-cigarettes as a smoking cessation aid.14 The FDA regulates ENDS.15 However, ENDS products are not FDA-approved for smoking cessation. There are several FDA-approved nicotine replacement therapies (NRTs) for this purpose, including three that are available over the counter (nicotine patches [Nicoderm CQ, Habitrol, and generic versions], nicotine lozenges [Nicorette and generic versions], and nicotine gum [Nicorette and generic versions]), and four by prescription, including two nonnicotine oral drugs (bupropion [Zyban] and varenicline [Chantix]), a nicotine nasal spray (Nicotrol NS), and nicotine inhalers (Nicotrol). Nicotine replacement dosage calculation is based on the patient's specific nicotine consumption, such as the number of cigarettes smoked and/or time to first morning cigarette, to ensure minimal withdrawal during the cessation process. Thus, there are ample well-tested FDA-approved products available for cessation. Quality control concerns At this time, there is no legally required quality control of ENDS products; therefore, these products are manufactured without FDA oversight of quality, according to D. Jenson, Lead Senior Staff Attorney for Federal Regulation, Public Health Law Center, Mitchell Hamline School of Law (e-mail communication, December 18, 2020). Three important quality control issues are highlighted, including inaccuracy of nicotine content, compounding-in-shop (CIS) processes of e-liquids, and FDA involvement. Inaccurate nicotine content. The American E-Liquid Manufacturing Standards Association (AEMSA) states that the nicotine content of all products containing e-liquids must be within 10% of the labeled amount.16 Almost half of the studies in a systematic review of e-liquid nicotine content found inaccurate nicotine labeling of ENDS products, with some samples varying more than 100% from the label.17-21 - ENDS use-associated risks ENDS factors compromising cessation efforts Lack of proven tobacco cessation efficacy Inability to accurately dose nicotine for tobacco cessation (risk of nicotine withdrawal and/or nicotine-related adverse reactions) Lack of quality control oversight Inaccurate nicotine content Inconsistencies of in-shop compounding and labeling Direct risks of ENDS use Youth exposure to nicotine Unknown safety of inhaling e-liquid additives Risk of acute e-liquid nicotine poisoning E-cigarette or vaping product use-associated lung injury Device battery fires/explosions The authors' 2019 study supports these findings, with only 3.8% of the 238 e-liquid samples meeting AEMSA guidelines.18,22 This cross-sectional study replicated and expanded on the authors' 2015 study assessing free-base, nicotine salt (salt), and 0-mg nicotine e-liquids from a variety of North Dakota shop types to determine nicotine content accuracy.22 The authors also examined the nicotine content of CIS samples. The CIS definition was adapted from Ribisl and colleagues and was specified as either an e-liquid made entirely on site or a premade liquid to which the shop staff added extra nicotine.23 Discrete data collection was completed in 35 (92.1%) of the shops meeting the criteria. Shop types were categorized as vape shops (n = 16, 45.7%), head shops with vaping products (n = 10, 28.6%), tobacco shops (n = 6, 17.1%), and other shops (n = 3, 8.6%). This study used discreet sampling methods so as to not alter the behavior of people in public places, such as the manager, workers, and patrons; therefore, data collectors acted as normal paying customers. Of the e-liquids (n = 285) purchased, 164 (57.5%) were free-base, 80 (28.1%) were salts, and 41 (14.4%) were identified as not containing any nicotine. The mean actual nicotine content was 34% below the labeled content, ranging from 93% below to 213% above the indicated content.22 None of the 25 CIS samples met the AEMSA guideline. In one shop, six samples were not labeled for nicotine content. When asked, the shop staff stated that all six contained the same nicotine content. However, the actual content ranged from just under 6 mg/mL to almost 20 mg/mL. CIS processes. CIS processes were observed during our 2019 study.22 CIS ingredients included nicotine, flavorings, and other chemicals. Vape shop staff used imprecise methods in compounding e-liquids, including visually estimating quantities of ingredients added. In one-third (two of six) of the shops where CIS processes were observed, shop staff did not relabel the nicotine content of the liquids. In one case, the nicotine content was increased from 0 mg/mL to 12 mg/mL without relabeling the bottle. Other labeling concerns included e-liquids sold without any labels, past their labeled expiration dates, and without an ingredient list.24 Another unprofessional practice included one shop being adjacent to a fish breeding room. Because of the inconsistencies in compounding and labeling, users cannot assume accuracy of e-liquid nicotine content. This has implications for individuals who are using e-liquids for cessation. Exposure to higher nicotine levels increases addiction risk. E-liquids with nicotine content lower than labeled may cause withdrawal symptoms. These are not concerns when using FDA-approved cessation products under the care of an NP. FDA involvement. The FDA requires ENDS manufacturers to file a premarket application; it is illegal to market these products without premarket authorization.25 However, most ENDS products have not been authorized by the FDA. It is of concern that given the overwhelming number of products available, the FDA states that they are unable “to take enforcement action against every illegally marketed tobacco product.”25 The FDA does not perform quality testing of e-cigarettes (D. Jenson, e-mail communication, May 11, 2021). Additionally, if there are no drug claims (such as for tobacco cessation), then there are neither specific quality standards or regulations for the manufacturing processes of e-cigarettes, nor for the end product (D. Jenson, e-mail communication, May 11, 2021). No e-cigarette or similar product has been approved as a drug product; therefore, no e-cigarettes are affected by the requirements that apply to FDA-regulated drugs (D. Jenson, e-mail communication, May 11, 2021). Concerns related to using e-liquids and ENDS for quitting tobacco use E-cigarette use is a particularly compelling nicotine option for cigarette users because it mimics both the physiologic satisfaction of a nicotine craving as well as the psychologic satisfaction of the act of smoking and responding to external cues that lead to smoking (time of day, social situations, behavioral triggers). The sensory and physical stimuli associated with cigarette smoking are deeply embedded aspects of smoking enjoyment and dependence (hand-to-mouth action, deep inhale/exhale, visual cues, throat hit, and tobacco flavor). The close imitation to cigarette smoking is one reason that cigarette users struggle with e-cigarette cessation, even when their original intention is to use e-cigarettes to stop all tobacco use.26 ENDS have been found to carry several health risks (see ENDS use-associated risks). Perhaps most concerning is the finding of e-cigarette or vaping product use-associated lung injury (EVALI) that emerged in 2019.27 EVALI is an acute pulmonary illness that has been associated with ENDS use, which can be severe and life-threatening, and is characterized by bilateral infiltrates on radiologic imaging.27 It has been shown that the e-liquid additive vitamin E acetate is strongly linked to EVALI.28 Additional ENDS-related health risks include the lack of safety data associated with inhaling many of the e-liquid additives, defective device batteries causing fires and explosions, and acute nicotine poisoning related to ingestion, inhalation, and topical absorption of e-liquids.29 Clinical guidelines relating to ENDS Nicotine users often ask whether ENDS are safe and effective and whether they can be used for cessation from traditional tobacco products. Many worldwide studies have attempted to answer that question. However, NPs and other clinicians face difficulties when interpreting such studies. First, ENDS products are not actively regulated; specific product analysis included in one study cannot be generalized to other products because of differences in the ENDS product devices as well as the liquid ingredients. Secondly, as mentioned, research shows that the actual nicotine content in ENDS products can vary, sometimes significantly, from their label.17,22 Finally, the puff patterns of ENDS users (how much of and how fast each puff is inhaled) are often not standardized in clinical trials, leading to wide variability of ENDS use, making comparisons difficult. Some clinical practice guidelines (CPGs) have tried to summarize all the studies to determine whether NPs can recommend ENDS products for tobacco cessation, which are described below. In 2018, the American College of Cardiology's Decision Pathway on tobacco cessation treatment recommended that “given the uncertainties of the long-term effects of e-cigarettes on health, a clinician should advise cigarette smokers seeking to quit to use evidence-based, FDA-approved, safe, and effective smoking cessation pharmacotherapies as first-line treatments in preference to e-cigarettes.”30 However, the document notes that some patients will choose to use ENDS products even if FDA-approved treatments are recommended. In those cases, the clinician should support the patient's effort to modify tobacco use and recommend use of ENDS products in the safest way possible (for example, avoid dual use of ENDS and cigarettes, ensure child-proof packaging and avoid using around children, and follow device instructions to minimize risk of explosion), with the goal of quitting both tobacco and ENDS products. In 2020, the American Thoracic Society's CPG for medication treatment in adults who use tobacco recommended that varenicline is a preferred treatment option over ENDS products.31 Studies evaluated in this CPG comparing varenicline with ENDS products showed that the benefit of varenicline over ENDS was uncertain; however, varenicline had fewer adverse reactions than ENDS products. Additional studies comparing varenicline with ENDS are needed to increase confidence in the recommendation. In 2021, the US Preventive Services Task Force (USPSTF) stated that “evidence on the use of e-cigarettes for tobacco smoking cessation in adults, including pregnant persons, is insufficient, and the balance of benefits and harms cannot be determined.”32 The USPSTF recommends that clinicians direct nonpregnant patients to FDA-approved pharmacotherapy and behavioral interventions for tobacco cessation.32 Clinicians are advised to direct pregnant persons to behavioral interventions. NPs should be aware of the many risks associated with ENDS products as well as the lack of evidence supporting the use of ENDS as a cessation method. Avoidance of ENDS products should be recommended; however, when that is not possible, approaching ENDS products in the same manner as other tobacco products would support patients' attempts to achieve both tobacco cessation and ENDS abstinence. Conclusion The science is still developing on the short- and long-term effects of ENDS on health and tobacco cessation efforts. Quality control of ENDS products is lacking. The actual nicotine content in ENDS products is often unknown, making it difficult to calculate the risk of replacing cigarettes with ENDS while ensuring equivalent levels of nicotine. Conversely, FDA-approved treatment medications are safe, effective, and have well-established dosing aimed at minimizing nicotine withdrawal and maximizing cessation success. Currently, there are no healthcare provider guidelines that recommend ENDS as a safe or effective means for cessation. The authors concur with current science-based guidelines that ENDS use for tobacco cessation is not recommended. NPs can instead recommend the cessation products approved by the FDA.