Epidemic of youth nicotine addiction? What does the National Youth Tobacco Survey 2017-2019 reveal about high school e-cigarette use in the USA?

Background: Between 2018 and 2020, the US Food and Drug Administration announced various restrictions on e-cigarette manufacturers in response to a perceived epidemic of e-cigarette use and nicotine dependence among high school students. The stimulus came from headline figures from the 2018 and 2019 National Youth Tobacco Survey (NYTS). We analysed e-cigarette use and dependence in the NYTS in relation to lifetime history of use of tobacco products. Design and setting: Nationally representative annual survey of high school students 2017 to 2019. Participants: 10,186 students in 2017, 10,991 in 2018 and 10,097 in 2019. Measurements: Any use of e-cigarettes in past 30 days, frequent e-cigarette use ( ≥ 20 of past 30 days) and indicators of tobacco or nicotine dependence (strong craving in past 30 days; wanting to use within 30 minutes of waking) were analysed in relation to lifetime tobacco product use history, ranging from never use through to lifetime smoking of >100 cigarettes. Findings: Past-30-day e-cigarette use increased from 11.7% in 2017 to 20.8% in 2018, and 27.5% in 2019. In 2019 it was reported in 13.3% of never tobacco users, 30.9% of those who had tried only a non-combustible product (OR 2.9, CI 1.9-4.5), and in 73.8 % of those who had smoked more than 100 cigarettes in their lifetime (OR 18.3, CI 8.4-40.1) Frequent use occurred in 1.0% of never tobacco users in 2018 and 2.1% in 2019. Among otherwise tobacco naive past-30-day e-cigarette users in 2019, 8.7% reported craving and 2.9% reported wanting to use within 30 minutes of waking. Conclusions: While use of e-cigarettes in US high-school students increased sharply between 2017 and 2019, frequent use and signs of e-cigarette dependence remained rare in students who had never used tobacco. Declarations of interest: JB received unrestricted research funding from Pfizer, who manufacture smoking cessation medications. RW undertakes research and consultancy for and receives travel funds and hospitality from manufacturers of smoking cessation medications (Pfizer, GlaxoSmithKline and Johnson and Johnson). All authors declare no financial links with tobacco companies or e-cigarette manufacturers or their representatives.


Introduction
On November 15th 2018, the US Food and Drug Administration (FDA) released preliminary findings from the National Youth T obacco Survey (NYT S) detailing ecigarette use in 2018 among US high school students (1). Compared with 2017, a 78% increase in past-30-day e-cigarette use was noted (1). At the same time, the FDA put out a press statement quoting HHS Secretary Alex Azar: "T hese new data show that America faces an epidemic of youth e-cigarette use, which threatens to engulf a new generation in nicotine addiction."(2) A statement from (then current, now former) FDA Commissioner Scott Gottlieb, issued on the same day, said: "T he data from this nationally representative survey…. show astonishing increases in kids' use of e-cigarettes and other ENDS, reversing years of favorable trends in our nation's fight to prevent youth addiction to tobacco products. T hese data shock my conscience"(3). Gottlieb announced a series of regulatory initiatives to address the perceived problem of youth ecigarette use.
T he FDA interpretation of the 2019 NYT S data continued in a similar vein. In congressional testimony Mitch Zeller, Director of the Center for T obacco Products summarised the "FDA's aggressive actions to address the youth epidemic of ENDS product use" (4), and on 2nd January 2020 the FDA issued a further enforcement policy.
In the accompanying press statement, a quote from HHS Secretary Alex Azar asserted that "T he United States has never seen an epidemic of substance use arise as quickly as our current epidemic of youth use of e-cigarettes." (5) T he NYT S contains extensive data on use of a range of tobacco products, and also documents self-reported dependence. Yet, the FDA's own publicly revealed analyses did not consider how e-cigarette use in high school students was related to patterns of use of other tobacco products, especially cigarettes and other combustible tobacco products, and did not present any analyses assessing dependence. Secondary analyses of the publicly available 2018 data have emphasised the importance of the overall tobacco context by showing that the large increases in prevalence of past 30-day use of e-cigarettes were characterized by patterns of low vaping frequency and high multiple tobacco product use. (6) In the UK, use of e-cigarettes by adolescents has not attracted such concern or policy intervention. Commentators have noted that e-cigarette use is strongly associated with cigarette smoking in young people and is very rare amongst never smokers (7)(8)(9). T he NYT S public use data file for the 2019 survey became available in January 2020. T his paper combines this with earlier data (10) to analyse e-cigarette use and indicators of tobacco dependence in the NYT S in relation to lifetime history of other tobacco products. We used data from the 2014 and 2015 NYT S to examine which product was tried first in tobacco users' careers. We also report on time trends in prevalence of e- and ever-use (ever trying) are ascertained. After being conducted via paper and pencil questionnaires since its inception in 1999, the NYT S was administered in schools using an electronic data collection method for the first time in 2019.
We derived a measure of lifetime tobacco product use history as follows: Respondents were asked "About how many cigarettes have you smoked in your entire life?" with 7 response options ranging from "I have never smoked cigarettes, not even one or two puffs" through "100 or more cigarettes (5 or more packs)". We added further categories for those who reported ever-use of e-cigarettes but no other tobacco product; a noncombustible tobacco product, but never any combustible; and use of a combustible product (cigars, pipes, bidi, hookah) but never cigarettes. T hus, there were 10 response categories in all for lifetime tobacco use history, ranging from never use of any tobacco product (tobacco naïve) through to smoking of more than 100 cigarettes.

Statistical analysis
We used the complex survey analysis module in SPSS 24 to adjust for the sampling design of the survey and to generate estimates (±95% confidence intervals) applicable to the US population. We examined the univariate association between current use of ecigarettes and our measure of lifetime tobacco product use history. We employed a logistic regression analysis to derive estimates of the odds ratios (±95% CIs) for current e-cigarette use. We conducted similar analyses to examine use of e-cigarettes for [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] days and 20 or more days within the past 30 days. We examined responses to two questions ("During the past 30 days, have you had a strong craving or felt like you really needed to use a tobacco product of any kind?"; and "How soon after you wake up do you want to use a tobacco product?" to provide an indication of dependence. We Which product used first by tobacco use history T able 3 shows, by lifetime tobacco use history, which product respondents reported using first in their tobacco career. T he more cigarettes students reported having smoked in their lifetime, the higher the chances were that cigarettes were the first product used: in 2014, just over three quarters (76.5%) of current e-cigarette users who had smoked more than 100 cigarettes named cigarettes as the first tobacco product they had used, while just 2.2% had used e-cigarettes first. Among those who had smoked 1 or more puffs but never a whole cigarette in their lifetime, 49.3% reported the cigarette as first product used and 18.8% had first used e-cigarettes. In 2015, 87.7% of current e-cigarette smokers who had smoked more than 100 cigarettes said cigarettes were the first product they had tried, while 7.6% identified e-cigarettes as the first product tried. Among those who had had smoked just 1 or more puffs of a cigarette in their lifetime, 53.1% had tried cigarettes first, and 25.4% had tried e-cigarettes first.
T rends in use of cigarettes, combustibles and e-cigarettes in NYT S 1999-2019 T here has been a continuing decline in current cigarette smoking in high school students, from 28.5% in 1999 to 8.1% in 2018 (see Figure). It is notoriously problematic to draw inferences about direction of causality from crosssectional data. In principle, the strong and graded association observed between likelihood of using e-cigarettes in the past 30 days and lifetime history of use of tobacco products could point to an effect of using e-cigarettes on subsequent uptake and use of cigarettes and other combustible products. T his appears to be the view adopted by the FDA. While it may well be the case that in some individual instances initial trying of an ecigarette led on to trying and using cigarettes, the data strongly suggest that this is not the dominant pattern observed at the level of the whole population. Among high school students we found that, for the great majority of those with any substantial cigarette smoking history, cigarettes were the first tobacco product tried, prior to any use of ecigarettes. Clearly, for these students their use of cigarettes and the development of characteristic nicotine dependence must be attributed to cigarettes as the uptake product, rather than to e-cigarettes. Similarly, the observed rapid decline in trying combustible products and in the prevalence of cigarette smoking since 1999 has not yet given any sign of being reversed through the upsurge of e-cigarette use since 2011 (12). At the population level, therefore, the NYT S fails to give evidence of e-cigarettes acting as a gateway to smoking in adolescents. Rather it seems that e-cigarettes may be displacing cigarettes and becoming the preferred nicotine product. In these circumstances, there is plausibility to the suggestion that, by helping adult smokers to quit, e-cigarettes are likely to reduce the overall tobacco disease burden in the USA (13).
We found little evidence of substantial nicotine addiction attributable to the use of e- tobacco could serve to reduce their chances of progression to using conventional tobacco products.
In summary, data from the NYT S survey do not provide support for claims of a new epidemic of nicotine addiction stemming from use of e-cigarettes, nor for concerns that declines in youth tobacco addiction stand to be reversed after years of progress. While use of e-cigarettes has increased markedly, especially since 2017, there has been no accompanying surge in nicotine dependence. Symptoms of dependence were rare among students who use e-cigarettes without having used any other tobacco products.
T his paper is not intended as a challenge to the current direction of FDA policy on the regulation of e-cigarettes. T hat would be presumptuous on our part. Rather, we have sought to examine the evidence brought forward to support new regulatory initiatives.
We find a gaping chasm between the vision of an epidemic of e-cigarette use threatening to engulf a new generation in nicotine addiction and the reality of the evidence contained in the NYT S. As patterns of youth nicotine and tobacco use continue to evolve, careful surveillance of survey findings will remain of critical importance.

Funding
Cancer Research UK funded SJ and JB's salary (C1417/A22962). T he funders had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or in the decision to submit the paper for publication. All researchers listed as authors are independent from the funders and all final decisions about the research were