New studies for UK, Netherlands and Flanders and US confirm gateway effects of e-cigs to combusted tobacco products

Three new studies add to the already overwhelming case that e-cigarettes are a gateway to combusted product use; two of these studies also show that combusted tobacco use predicts later e-cigarette use among youth. These studies are benefit from the fact that the data were collected relatively recently, which is important because e-cigarette technology is rapidly evolving with the newer e-cigarettes using protonated nicotine, which is easier to inhale that was pioneered by Juul.

Jeremy Staff and colleagues’ study “Adolescent electronic cigarette use and tobacco smoking in the Millennium Cohort Study” published in Addiction used the UK Millennium Cohort to examine the longitudinal association between e-cigarette and cigarette among youth who were 14 in January 2015 to March 2016 to when they were 17 in January 2018 to March 2019. They found that never smoking youth who used e-cigarettes when they were 14 had more than five times higher odds of initiating tobacco smoking by age 17 (adjusted odds ratio 5.25) and nearly triple the odds of being a frequent tobacco smoker at age 17 (aOR 2.91) after adjusting for risk factors and demographics.

They also found that smoking cigarettes predicted subsequent e-cigarette use: teenagers who had smoked tobacco cigarettes by age 14 had three times higher odds of initiating e-cigarettes by age 17 (aOR = 2.98) compared with non-tobacco smokers and nearly three times higher odds of frequently using e-cigarettes at age 17 (aOR = 2.90).

As a sensitivity analysis they also matched respondents who initiated nicotine use with e-cigarettes and cigarettes on several risk factor for smoking and found similar results (their Tables 4 and 5). While not a goal of their study, they found that about half the risk factors in childhood distinguished adolescent e-cigarettes users from non-users, compared to the age 14 tobacco smokers who were over-represented on almost all the risks (Table 4). This information is consistent with our (and others’) finding that many of the youth who initiate nicotine use with e-cigarettes would be unlikely to start with cigarettes, thereby expanding the tobacco epidemic (see this paper and the other papers cited in it).

This paper is particularly important for two reasons: First, is it from UK and England (which is part of the UK) remains a hotbed of e-cigarette enthusiasm with at least some health experts continuing to minimize the youth problem. Second, the odds of progression to cigarettes is higher than in earlier studies (although the confidence interval overlap), including in the UK (Figure S10 in Khouja et al), which may reflect the increasing addictiveness of the new generation e-cigarettes.

The second study, Thomas Martinelli and colleagues’ “Exploring the gateway hypothesis of e-cigarettes and tobacco: a prospective replication study among adolescents in the Netherlands and Flanders” in Tobacco Control, uses longitudinal data collected between September 2018 and December 2019 in the Netherlands and Flanders (the Dutch-speaking part of Belgium) to examine the associations between e-cigarette use and combusted tobacco (including cigarettes, cigars, little cigars, and hookah) among youth age around 13-14. Similar to the UK study, they found that baseline e-cigarette use was associated with over 5 times the combusted tobacco smoking a year later (aOR=5.63). They also found that more frequent use of e-cigarettes at baseline was associated with more frequent smoking at follow-up.

Baseline combusted tobacco smoking was also associated with about the same odds of subsequent e-cigarette use (aOR=3.10) as in the UK study.

Like the UK study, the odds of progression from e-cigarettes to cigarettes was higher than in the older studies. In addition, the odds of adopting e-cigs among smokers was lower than e-cig users adopting cigarettes or combusted products.

Finally, Elizabeth Hair and colleagues’ study “A longitudinal analysis of e-cigarette use and cigar, little cigar or cigarillo initiation among youth and youth adults: 2017-2019” published in Drug and Alcohol Dependence reported a longitudinal study that followed US 15-21 year olds from 2017-2019 to examine the association between e-cigarette use and initiation and current use of cigars, little cigars, or cigarillos. They found that the odds of initiating these products was more than tripled (OR: 3.30 for Juul users, 3.57 for other products). Odds of using these products were also increased (albeit with lower ORs) for people who used combustible cigarettes or marijuana.

These three studies point to the need to view e-cigarettes in the broader context of multiple tobacco product use and their role in expanding the tobacco epidemic and raise concerns that the newer generation e-cigarettes are having stronger effects. These findings also reinforce the importance that the FDA and other regulatory agencies consider these factors when assessing how authorizing a new tobacco product adversely impacts non-users of other tobacco products.

Here is the abstract for the Staff et al study:

Aims. To evaluate the catalyst, diversion and common liability hypotheses by examining associations between e-cigarette use and tobacco cigarette smoking at modal ages 14 and 17 years, controlling for adolescent and infancy risk factors.

Design. Intergenerational, prospective cohort data from the Millennium Cohort Study (MCS). Nationally representative sample of infants born September 2000 to January, 2002.

Setting. United Kingdom. Participants Parent and child data from 10 625 youth assessed in infancy and modal ages 11, 14 and 17 years.

Measurements. Age 14 and 17 e-cigarette and combustible cigarette use (recency, frequency). Potential confounders were age 11 risk factors (e.g. alcohol use, externalizing behaviors, parental tobacco use, permissiveness), infancy risk factors (e.g. maternal smoking during pregnancy, smoke exposure in infancy) and demographic characteristics.

Findings. Among youth who had not smoked tobacco by age 14 (n = 9046), logistic regressions estimated that teenagers who used e-cigarettes by age 14 compared with non-e-cigarette users, had more than five times higher odds of initiating tobacco smoking by age 17 [odds ratio (OR) = 5.25, 95% confidence interval (CI) = 3.28–8.38] and nearly triple the odds of being a frequent tobacco smoker at age 17 (OR = 2.91, 95% CI = 1.56–5.41), net of risk factors and demographics. Among youth who had not used e-cigarettes by age 14 (n = 9078), teenagers who had smoked tobacco cigarettes by age 14 had three times higher odds of initiating e-cigarettes by age 17 (OR = 2.98, 95% CI = 1.74–5.09) compared with non-tobacco smokers and nearly three times higher odds of frequently using e-cigarettes at age 17 (OR = 2.90, 95% CI = 1.21–6.95), net of confounders. Similar links between e-cigarette and tobacco cigarette use were observed in regressions following coarsened exact matching.

Conclusions. E-cigarette use by age 14 is associated with increased odds of tobacco cigarette initiation and frequent smoking at age 17 among British youth. Similarly, tobacco smoking at age 14 is associated with increased odds of both e-cigarette initiation and frequent use at age 17.

The full citation is: Staff J, Kelly BC, Maggs JL, Vuolo M. Adolescent electronic cigarette use and tobacco smoking in the Millennium Cohort Study. Addiction 2021; 19 July 2021 https://doi.org/10.1111/add.15645.  It is available here.

Here is the abstract for the Martinelli et al paper:

Background: Studies demonstrated that adolescent e-cigarette use is associated with subsequent tobacco smoking, commonly referred to as the gateway effect. However, most studies only investigated gateways from e-cigarettes to tobacco smoking. This study replicates a cornerstone study revealing a positive association between both adolescent e-cigarette use and subsequent tobacco use; and tobacco and subsequent e-cigarette use in the Netherlands and Flanders. 

Design: The longitudinal design included baseline (n=2839) and 6-month (n=1276) and 12-month (n=1025) follow-up surveys among a school-based cohort (mean age: 13.62). Ten high schools were recruited as a convenience sample. The analyses involved (1) associations of baseline e-cigarette use and subsequent tobacco smoking among never smokers; (2) associations of e-cigarette use frequency at baseline and tobacco smoking frequency at follow-up; and (3) the association of baseline tobacco smoking and subsequent e-cigarette use among non-users of e-cigarettes.

Findings: Consistent with prior findings, baseline e-cigarette use was associated with higher odds of tobacco smoking at 6-month (OR=1.89; 95% CI 1.05 to 3.37) and 12-month (OR=5.63; 95% CI 3.04 to 10.42) follow-ups. More frequent use of e-cigarettes at baseline was associated with more frequent smoking at follow-ups. Baseline tobacco smoking was associated with subsequent e-cigarette use (OR=3.10; 95% CI 1.58 to 6.06 at both follow-ups).

Conclusion: Our study replicated the positive relation between e-cigarette use and tobacco smoking in both directions for adolescents. This may mean that the gateway works in two directions, that e-cigarette and tobacco use share common risk factors, or that both mechanisms apply.

The full citation is: Martinelli T, Candel MJJM, de Vries H, Talhout R, Knapen V, van Schayck CP, Nagelhout GE. Exploring the gateway hypothesis of e-cigarettes and tobacco: a prospective replication study among adolescents in the Netherlands and Flanders. Tob Control. 2021 Jul 5:tobaccocontrol-2021-056528. doi: 10.1136/tobaccocontrol-2021-056528. Epub ahead of print. PMID: 34226262. It is available here.

Elizabeth Hair and colleagues at Truth Initiative recently published “A longitudinal analysis of e-cigarette use and cigar, little cigar or cigarillo initiation among youth and youth adults: 2017–2019” that found that the odds of youth and young adults who had ever used JUUL or other e-cigarettes going on to use cigars, little cigars or cigarillos was more than three times greater compared to never users of e-cigarettes.

Here is the abstract for the Hair et al paper:

Purpose.  To examine whether youth and young adult e-cigarette use is associated with initiation of cigars, little cigars, or cigarillos (CLCCs) and current use of flavored CLCCs. 

Basic procedures. The sample is drawn from the Truth Longitudinal Cohort, a probability-based longitudinal cohort of youth and young adults recruited at ages 15–21 and surveyed every six months. The sample for this study was CLCC-naïve defined as those who had never used CLCCs as of 2017 (N = 5586). The outcomes were the odds of (1) initiating any CLCC use and (2) reporting current (past 30-day) use of flavored CLCCs from 2018 to late 2019. The main predictor was use of e-cigarettes by 2018. 

Results. The odds of initiating a CLCC was greater for those who had used ever used JUUL (OR: 3.30, p < 0.001) or were current users of another type of e-cigarette by 2018 (OR: 3.57, p < 0.001). Odds of CLCC initiation was also greater for those who had ever used combustible cigarettes (OR: 1.62, p < 0.05), were current smokers (OR: 3.12, p < 0.001) or had used marijuana (OR: 1.92, p < 0.001) by 2018. E-cigarette use that occurred by 2018 was associated with greater odds of current use of flavored CLCCs compared to non-flavored CLCCs (ever users of JUUL: OR: 2.57, p < 0.01; current users of some other e-cigarette: OR: 3.06, p < 0.05). 

Conclusion and relevance. This study raises new concerns about the effects of e-cigarette use on subsequent combustible tobacco use. Restrictions on CLCCs should be considered in conjunction with current policies designed to reduce the youth vaping epidemic.

The full citation is: Hair EC, Kreslake JM, Mowery P, Pitzer L, Schillo B, Vallone DM. A longitudinal analysis of e-cigarette use and cigar, little cigar or cigarillo initiation among youth and youth adults: 2017-2019. Drug Alcohol Depend. 2021 Sep 1;226:108821. doi: 10.1016/j.drugalcdep.2021.108821. Epub 2021 Jun 23. PMID: 34218009. It is available here.

Published by Stanton Glantz

Stanton Glantz is a retired Professor of Medicine who served on the University of California San Francisco faculty for 45 years. He conducts research on tobacco and cannabis control and cardiovascular disease/

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