ELECTRONIC CIGARETTES : AN OVERVIEW OF KEY ISSUES

to deliver the addictive substance nicotine without burning tobacco. A 2018 report from the National Academies of Sciences, Engineering, and Medicine (NASEM) found that e-cigarettes are less harmful than cigarettes, but are not risk-free.1 The report also found that many questions remain about the long-term health effects of these products for individual users and about the population-wide effects. In a 2020 report, the Surgeon General found that “the long-term health effects of using these products remain unknown, and short-term risks are only slowly coming into focus.”2

Unlike cigarette and smokeless tobacco companies, e-cigarette companies are not currently required to report their marketing and promotional expenditures to the U.S. Federal Trade Commission (FTC), so the exact amount spent to advertise and promote these products is uncertain. Studies of e-cigarette marketing expenditures found dramatic increases in the early years. 17 Analysis of more recent marketing spending found a decline between 2014 and 2017, but then a more than doubling between 2017 and 2018, to $110 million. Juul accounted for the majority of spending that year. 18 These figures likely underestimate the true extent of e-cigarette advertising, as the available marketing data are not comprehensive (e.g., social media and sponsored events-strategies widely used by numerous ecigarette companies-are not included).
Social media helps to fuel the popularity of e-cigarettes, including the top-selling e-cigarette brand, Juul. A study analyzing Juul marketing noted that Juul was one of the first major e-cigarette brands to rely heavily on social media to market and promote its products. The study found that Juul's initial marketing expenditures in traditional channels were modest compared to competing brands, and that these expenditures decreased as the brand increased content and received more promotion on social media channels like Instagram and Twitter. 19 These advertising efforts have effectively reached youth and young adults. The Surgeon General concluded that, "E-cigarettes are marketed in a wide variety of channels that have broad reach among youth and young adults." 20 The 2019 National Youth Tobacco Survey (NYTS) found that 69.3% of middle and high school students -18.3 million youth -had been exposed to e-cigarette advertisements from at least one source. 21 A 2016 study in Pediatrics, analyzing 2014 NYTS data, found that exposure to ecigarette advertising is associated with current e-cigarette use among youth and that greater exposure to e-cigarette advertising is associated with higher odds of use. 22 Use of E-Cigarettes Among Adults and Youth E-cigarettes have been the most popular tobacco product among youth since 2014, and the number of youth using e-cigarettes is alarming and raises serious concerns. It is still an open scientific question whether e-cigarettes might be able to help adult smokers give up cigarettes; however, kids should not be using any tobacco product, including e-cigarettes.
While e-cigarettes have become increasingly popular among youth and young adults, uptake has remained low among older adults. About 25% of all e-cigarette users in the US are youth, and 44% are under age 25. 23 Youth Use. According to the NYTS, high school ecigarette use declined to 19.6% in 2020, after increasing by 135% from 2017 to 2019 (from 11.7% to 27.5%). 24 Among middle school students, e-cigarette use declined to 4.7% in 2020, after more than tripling from 2017 to 2019 (from 3.3% to 10.5%). While the significant decline in youth users since 2019 is a sign of progress, youth e-cigarette use remains high. In 2020, 3.6 million kids still use e-cigarettes -the same number as when the U.S. Surgeon General called youth ecigarette use an "epidemic" in 2018. 25 The same survey found that among those who had used e-cigarettes in the past 30 days, an increasing proportion of youth e-cigarette users are showing signs of addiction. In 2020, 38.9% of high schoolers used e-cigarettes on at least 20 of the preceding 30 days (up from 34.2% in 2019). Twenty percent of middle school users were frequent users of e-cigarettes (up from 18% in 2019). Alarmingly, 22.5% of high school e-cigarette users and 9.4% of middle school e-cigarette users were daily users, a strong indication of addiction. This amounts to 1.3 million middle and high school students who were frequent users of e-cigarettes, including over 730,000 daily users. 26 Data from another national survey, the 2019 Monitoring the Future study, found that one out of nine high school seniors (11.7%) report that they vaped nicotine nearly daily. 27 Multiple national surveys show that flavored e-cigarettes are popular among youth. Data from the 2016-2017 wave of FDA's Population Assessment of Tobacco and Health (PATH) study found that 96.1% of 12-17 year olds who had initiated e-cigarette use since the last survey wave started with a flavored product. Additionally, it found that 97% of current youth e-cigarette users had used a flavored e-cigarette in the past month and 70.3% say they use e-cigarettes "because they come in flavors I like." 28 More recently, the 2020 NYTS found that an increasing proportion of middle and high school e-cigarette users reported using flavored products in 2020 (82.9%, up from 68.8% in 2019). Among high school students who currently used any type of flavored e-cigarette, the most commonly used flavor types were fruit (73.1%), mint (55.8%), menthol (37%), and candy, desserts, or other sweets (36.4%). 29 While the methodology is not comparable to the PATH study, both surveys confirm that flavors are an important reason youth use e-cigarettes.  Among youth, the most popular e-cigarette devices are refillable cartridge (or "pod") systems like Juul. In 2020, about half (48.5%) of high school e-cigarette users reported that their most commonly used device type was prefilled pods or cartridges. However, disposable e-cigarettes like Puff Bar and Mojo have surged in popularity among youth due to the wide array of flavors that are now prohibited in cartridge systems. Among high school current e-cigarette users, use of disposable e-cigarettes increased by 1,000% from 2019 to 2020 (from 2.4% to 26.5%). 30 Adult Use. Data from the National Health Interview Survey (NHIS) show that in 2019, 4.5% of adults currently used e-cigarettes every day or some days, an increase from 3.2% in 2018. 31 • E-cigarette use is highest among younger adult populations. Compared to 3.0% of 45-64 year olds, 9.3% of 18-24 year olds currently use e-cigarettes every day or some days, an increase from 7.6% in 2018. Among all tobacco products, e-cigarettes were used by the highest proportion of 18-24 year olds (24.5%). • A higher percentage of White, non-Hispanic adults use ecigarettes (5.1%) compared to Black, non-Hispanic adults (3.4%) or Hispanic adults (2.8%).
Trend analysis of NHIS data showed that in 2018, 38% of younger adult (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) year old) e-cigarette users had never been cigarette smokers, which was a considerable enough increase from 2014 that it "represented the largest absolute increase in e-cigarette users (additional 0.87 million users) among all age groups." 32 Similarly, data from the Behavioral Risk Factor Surveillance System (BRFSS), show that the proportion of young adult never smokers using e-cigarette users roughly doubled between 2016 and 2018, while e-cigarette use rates among older adult never smokers changed very little. 33 This discrepancy continued in 2019, with NHIS data showing that more than half of [18][19][20][21][22][23][24] year-old current e-cigarette users (56.0%) had never smoked cigarettes, the highest proportion among the age groups. This youngest adult age group also had the lowest percentage of e-cigarette users who were former smokers. 34

Health and Public Health Concerns
Under the right circumstances, e-cigarettes could benefit public health if they help significantly reduce the number of people who use combustible cigarettes and die of tobacco-related disease. However, these potential benefits must be weighed against the current epidemic of use among youth. As the Surgeon General stated in a 2020 report, "The potential benefit of e-cigarettes for cessation among adult smokers cannot come at the expense of escalating rates of use of these products by youth." 35 According to CDC and the 2018 NASEM report on e-cigarettes, e-cigarettes are less harmful than combustible cigarettes, but that doesn't mean that they are safe or without risk. 36 The Surgeon General found that "the long-term health effects of using these products remain unknown, and short-term risks are only slowly coming into focus." The NASEM report stated that "the absolute risks of the products cannot be unambiguously determined at this time," and there is little data to assess the impact on cancer and heart disease risk. 37 Thus, many questions still remain about the potential long-term risks to the public health posed by these products.

E-cigarette ingredients and constituents.
There is insufficient research on the long-term effects of using e-cigarettes, which involves regular inhalation of nicotine, glycerin or some other solvent, and other additives. 38 According to the Surgeon General, "E-cigarette aerosol is not harmless. It can contain harmful and potentially harmful constituents, including nicotine." 39 The nicotine present in e-cigarette aerosol is absorbed by users and bystanders. 40 Studies have found other chemicals and toxins present in some ecigarettes, including formaldehyde, acrolein, volatile organic compounds like toluene, tobacco-specific nitrosamines, and metals like nickel and lead. 41 These compounds are generally present at levels much lower than in cigarette smoke, although the compounds themselves are found on FDA's list of harmful or potentially harmful substances. 42  Adult Current E-Cigarette Use available in hundreds of different brands, 43 there is no way for consumers to know for sure yet what is in the products or the aerosol. 44 In addition, while some of the other substances, such as flavorings, used in e-cigarettes might be labeled as "generally recognized as safe," some researchers as well as the organization primarily responsible for granting that designation 45 have noted that it applies to ingestion, not for other exposures such as inhalation. The NASEM report committee expressed concern about flavor additives because even todate, they "have not been widely tested for sensitizing, toxic, or irritating potency." 46 In its 2016 report, the Surgeon General stated that, "while some of the flavorings used in e-cigarettes are generally recognized as safe for ingestion as food, the health effects of their inhalation are generally unknown" and noted that some of the flavorings found in e-cigarettes have been shown to cause serious lung disease when inhaled. 47 An article in the Journal of the American Medical Association raised concerns that the chemical flavorings found in some e-cigarettes and e-liquids could cause respiratory damage when the e-cigarette aerosol is inhaled deeply into the lungs. 48 FDA has been investigating a possible link between e-cigarettes and seizures, finding that more than 125 incidents, particularly among youth and young adults, have been reported between 2010 and 2019. 49 Impact of Nicotine. E-cigarettes and refill liquids contain widely varying levels of nicotine, and the nicotine delivered through the aerosol can also vary depending on the device characteristics and user practices. 50 More recently, e-liquids have been formulated with nicotine salts, which, according to the Surgeon General, "allow particularly high levels of nicotine to be inhaled more easily and with less irritation than the free-base nicotine that has traditionally been used in tobacco products, including e-cigarettes." 51 While ecigarettes can be used for non-nicotine products, including marijuana, the vast majority of e-cigarette products sold in traditional retail stores contain nicotine, 52 and more than two-thirds of youth e-cigarette users report using e-cigarettes exclusively for nicotine-containing products. 53 Nicotine is a highly addictive drug that can have lasting damaging effects on adolescent brain development and has been linked to a variety of adverse health outcomes for the developing fetus. 54 The Surgeon General concluded that, "The use of products containing nicotine poses dangers to youth, pregnant women, and fetuses. The use of products containing nicotine in any form among youth, including in ecigarettes, is unsafe." 55 In general, nicotine has been found to impact the cardiovascular system. 56 The NASEM report found that the nicotine in e-cigarettes can increase heart rate and diastolic blood pressure in users shortly after use, but evidence was not available to determine an association between e-cigarette use and other cardiovascular outcomes such as heart disease and stroke. However, the NASEM report acknowledged that the nicotine in e-cigarettes could elevate cardiovascular disease risk in users with pre-existing cardiovascular disease. 57 Poisoning and Exposure to Liquid Nicotine. Delivered in high doses, nicotine can be lethal. The Surgeon General's 2016 report and the NASEM report both found that contact with e-liquids can cause adverse health effects and ingesting e-liquids can lead to death. 58 Exposure to liquid nicotine found in e-cigarettes has resulted in thousands of calls to poison control centers in recent years, according to the American Association of Poison Control Centers (AAPCC). 59 In 2014, more than half of these calls to poison hotlines were to report exposures among children under the age of six. 60 To begin to address the poisoning risk that ecigarettes and liquid nicotine pose to young children, in 2016 Congress passed the Child Nicotine Poisoning Prevention Act, which gave the Consumer Product Safety Commission authority to enforce child resistant packaging standards for e-cigarette products. This law went into effect in July 2016.

Population-Level Health Concerns
Youth and Young Adults. The number of youth using e-cigarettes raises serious concerns that ecigarettes may function as a gateway to the use of more dangerous, combustible tobacco products.
• The Surgeon General found that while more research is needed, e-cigarette use is "strongly associated" with the use of other tobacco products among youth and young adults, including conventional cigarettes. 61 • The NASEM report concluded that "[t]here is substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults." 62 • An analysis of data from the FDA's nationally representative Population Assessment of Tobacco and Health (PATH) study found that from 2013 to 2016, youth (ages 12-15) e-cigarette use was associated with more than four times the odds of trying cigarettes and nearly three times the odds of current cigarette use. The researchers estimate that this translates to over 43,000 current youth cigarette smokers who might not have become smokers without e-cigarettes. 63 • New research shows that the latest generation of high nicotine e-cigarettes like Juul that have fueled the youth e-cigarette epidemic are also associated with subsequent smoking initiation. An analysis of 2017-2019 data from the Truth Longitudinal Cohort, a study of young and young adults (ages [15][16][17][18][19][20][21][22][23][24][25][26][27], found that compared with those who had never used an e-cigarette, those who reported ever use of any e-cigarette (Juul or other brands) in 2018 had significantly higher odds of ever cigarette use one year later, and those who reported ever use of Juul in 2018 had significantly higher odds of current e-cigarette use one year later. 64 Dual Use and Cessation. Data show that a significant number of e-cigarette users report using both ecigarettes and conventional cigarettes, raising additional concerns beyond the potential health effects of e-cigarettes alone.
Many e-cigarette users report using both e-cigarettes and cigarettes. According to the 2019 NHIS, 36.9% of adult e-cigarette users are also current cigarette smokers (dual users). 65 Little data are available on what happens with dual users over time. Analysis of PATH data found that nearly 9 out of 10 early dual users were still smoking cigarettes at follow-up. Among adults who were dual users of e-cigarettes and cigarettes at Wave 1 (2013-2014), 44.3% maintained dual use, 43.5% discontinued e-cigarette use but maintained cigarette smoking, and only 12.1% discontinued cigarette use (5.1% discontinued cigarette use but continued e-cigarette use and 7.0% discontinued use of both products) at Wave 2 (2014-2015). 66 A study using 2013-2014 PATH data found that dual users had toxicant exposures that were similar to those who only used cigarettes. 67 Some e-cigarette users report that they believe that e-cigarettes will help them quit or reduce the number of cigarettes they smoke. 68 While existing research is limited and provides mixed results about the effectiveness of e-cigarettes in helping current smokers successfully quit, leading public health authorities have found that there is not enough evidence to conclude whether e-cigarettes are a safe and effective smoking cessation device. 69 • The 2020 Surgeon General Report on Smoking Cessation, released in January 2020, concluded that "there is presently inadequate evidence to conclude that e-cigarettes, in general, increase smoking cessation." The Surgeon General also cautions that because e-cigarettes are not a single product, but "a continually changing and heterogeneous group of products" that "are used in a variety of ways," it is difficult to make broad generalizations about the efficacy of e-cigarettes for smoking cessation based upon any one study or any one product. 70 • The U.S. Preventive Services Task Force, which makes recommendations about the effectiveness of specific preventive care services after a thorough assessment of the science, concluded that "the current evidence is insufficient to recommend electronic nicotine delivery systems for tobacco cessation..." 71 • The NASEM report concluded, "[o]verall, there is limited evidence that e-cigarettes may be effective aids to promote smoking cessation." 72 • According to researchers from the CDC, "There is currently no conclusive scientific evidence that e-cigarettes promote long-term cessation, and e-cigarettes are not included as a recommended smoking cessation method by the U.S. Public Health Service." 73 However, some research does suggest some types of e-cigarettes used under certain conditions may help smokers quit. For example, a study published in the New England Journal of Medicine (NEJM) found that certain electronic cigarettes may be effective at helping smokers quit traditional cigarettes when combined with behavioral support. The study, of smokers attending stop smoking services through the U.K. National Health Service, found that at one year follow-up, the quit rate among smokers in the e-cigarette group was 18%, compared to 9.9% in the nicotine-replacement group. 74 A 2018 longitudinal study using PATH data found that cigarette smokers who used e-cigarettes daily had significantly greater odds of quitting compared to non e-cigarette users. 75 Product type is also an important factor, with one study noting that while daily use of tank-based or non-cartridge based e-cigarettes increases the likelihood of cessation, other types of e-cigarettes do not, even when used daily. 76 Two recent studies using PATH data reinforce findings from earlier studies that using e-cigarettes was no more effective in helping smokers quit compared to nicotine replacement therapy (NRT) or other FDAapproved pharmacotherapies. However, like the NEJM study described earlier, these studies found that the majority of those who used e-cigarettes to quit smoking were continuing to use e-cigarettes afterwards. 77 Similarly, two older randomized controlled trials found that e-cigarettes are moderately effective in helping smokers quit, with rates of cessation with e-cigarettes similar to rates of cessation with nicotine replacement therapy (NRT). 78 Other studies have found that e-cigarette use is not associated with successful quitting, finding that ecigarette users were not more likely to have quit smoking compared to non-users. 79 A 2018 study by Weaver et. al., did not find any evidence that ENDS help adult smokers quit at a higher rate than smokers who did not use these products despite ENDS users being more likely to make a quit attempt. In fact, the authors state that "findings indicate that, at the time of this study, ENDS under "real world" use and conditions may have suppressed or delayed quitting among some adult smokers." 80 A meta-analysis of 38 studies that examined the association between e-cigarette use and smoking cessation among adult smokers found that the odds of quitting were less among smokers using e-cigarettes. 81 A study of current and former cigarette smokers found that e-cigarette users significantly reduced the number of cigarettes smoked per day compared to non-users, although at follow-up, e-cigarette users were not more likely to have quit smoking compared to non-users. 82 A more recent study (Weaver et. al.) did not find that the use of ENDS was associated with a reduction in cigarette consumption among those participants who had not quit smoking at follow-up. 83 Reducing the number of cigarettes smoked is a good thing if it eventually leads to quitting completely. However, e-cigarettes could ultimately reduce the number of smokers who would otherwise quit if smokers continue to use them in addition to, and not instead of, regular cigarettes. This would have a negative impact on public health. Smokers who continue to smoke (even fewer cigarettes per day) but also use e-cigarettes will increase their individual risk if this delays or prevents cessation. The NASEM report stated that a "reduction in rate of smoking does not ensure reduction in tobacco-related harm" and that, "there is no available evidence whether or not longterm e-cigarette use among smokers (dual use) changes morbidity or mortality compared with those who only smoke combustible tobacco cigarettes." 84 Furthermore, CDC has highlighted the importance of quitting cigarettes completely, not just cutting down. According to the CDC, "If you only cut down the number of cigarettes you smoke by adding another tobacco product, like e-cigarettes, you still face serious health risks. Smokers must quit smoking completely to fully protect their health -even a few cigarettes a day are dangerous." 85 Several Surgeon General's Reports and other studies have indicated that the risk of cardiovascular disease and other smoking-related diseases depends largely on the length of time a person smokes, not just the number of cigarettes smoked. Compared to non-smokers, light and intermittent smokers are at greater risk for cardiovascular diseases, lung cancer and lower respiratory tract infections, among other things. 86 Studies have found that smoking just one to four cigarettes a day increases the risk of developing or dying from heart diseases. 87 A recent review of 141 studies that examined the relationship between cigarette consumption and the risk for cardiovascular disease and stroke found that smoking even one cigarette per day carries a very high risk for developing cardiovascular disease and stroke. The authors concluded that, "Smokers need to quit completely rather than cut down if they wish to avoid most of the risk associated with heart disease and stroke." 88 Thus, prolonging smoking, despite smoking fewer cigarettes from using e-cigarettes, will continue to put that person's health at greater risk than if he or she had quit smoking entirely. 89

Important unanswered questions:
• What are the long term health impacts of e-cigarette use?
• Do e-cigarettes help smokers quit more effectively than FDA-approved cessation products?
• Currently, half of e-cigarette users continue to smoke cigarettes. Will most e-cigarette users continue to be dual-users, or will they switch completely and become exclusive users of ecigarettes?
• Will e-cigarette marketing renormalize tobacco use?
• Research shows a strong association between e-cigarette use and subsequent combustible cigarette smoking among youth and young adults. Will that translate into increased smoking rates in the long-term?
• Do e-cigarettes draw former smokers back into nicotine addiction and potentially back to cigarette smoking?
There are many important unanswered questions regarding the short and long-term impact that ecigarettes may have on public health. Effective regulation is needed to minimize the potential harms of ecigarettes and maximize any potential benefits.