“The new crisis is hitting schools in South Africa,” an alarming headline from the BusinessTech website on 4 November 2022.(1) The article reported on a study from Cape Town, which revealed that more than one in four matric learners are vaping. More worrying were signs of nicotine dependence, as three out of 10 respondents admitted using their electronic smoking device within an hour of waking, and nearly a quarter cannot get through a school day without vaping. While this study was performed at high-income schools in Cape Town, educators across all school income levels report similar trends. Why is this such a worry to us? Preventing lifelong nicotine addiction in adolescents is the cornerstone to preventing smoking-related mortality and morbidity.
Worldwide, the overall trend over the last 20-plus years has seen a significant decline in the percentage of youths using tobacco products. In the United Kingdom (UK), current (<1 cigarette/week) and regular (≥1 cigarette/ week) smoking rates among adolescents (11–15 years) fell dramatically from 1996 to 2016 (22% to 6% and 10% to 3%, respectively).(2) In the United States (US), the prevalence of past 30-day cigarette smoking declined linearly from 15.8% to 7.6% among 9–12 grade students (14–18 years) between 2011 and 2017.(3)
This decline in smoking prevalence in high-income countries is being challenged by the surge in the popularity of electronic nicotine delivery systems (ENDS), commonly called e-cigarettes or vapes. ENDS use among 11–15-year-olds in England increased from 22% in 2014 to 25% in 2016. In the US, estimates suggest that since 2011, past 30-day e-cigarette use has risen sharply from 1.5% to 20.8% among grade 9–12 students.(4) This alternative form of nicotine consumption has now surpassed all the progress with the decline of tobacco products.
South African (SA) data comes from a recent systematic review and meta-analysis of studies conducted in SA among adolescents and young adults aged 12–24 from 2000 until 2023, found that the pooled prevalence of current tobacco use among South African adolescents and young adults was estimated to be 22% and in secondary school learners 16%.(5) While these figures are higher than those of the UK and US, they correspond with data from other low to middle-income countries.(6) What is worrying is that on top of the high rates of adolescent smoking, we, too, are having an ENDS epidemic. In the South African E-Cigarette Survey undertaken by the Tobacco Control Data Initiative in 2022, 7.7% of individuals between 18-24 used ENDS, the highest across all age groups surveyed.(7) (Fig. 7.1) Alarmingly, among responders using ENDS with no prior history of tobacco smoking, 19% started using conventional cigarettes as well (Fig 7.2).
How SA and the rest of the world ended up at this crossroads again of adolescent nicotine dependence after a significant decline in learners using tobacco is a complicated story involving the tobacco industry's hidden agendas, harm reduction lobbyists, slow government legislation, and incorrect interpretation of scientific papers.
The first commercially available modern ENDS was developed by a Chinese pharmacist, Hon Lik, in 2003. When the patent was registered in 2004, the Chinese company Ruyan began marketing their product to the local Chinese market, then arrived in the US in 2007.(8,9) ENDS arrived in SA in the early 2010s. The first Ruyan product in the US used the term “an electronic atomization cigarette that functions as a substitute for quitting smoking and cigarette substitutes” in their patent application.(9) In both the US and SA, there has been a constant struggle between the government and ENDS manufacturers about the classification of tobacco products, resulting in delays in regulating sales and advertising. This has only exacerbated the growing adolescent burden of e-cigarette use.(9,10) The South African “Control of Tobacco Products and Electronic Delivery Systems Bill” is yet to be passed, even though it was initially proposed in May 2018.(11) Thus, ENDS can be sold openly in public spaces and advertised freely in SA.
In 2014, International Respiratory Societies, including the South African Thoracic Society, published a position paper on ENDS stating, “The health and safety claims regarding electronic nicotine delivery devices should be subject to evidentiary review. The potential benefits of electronic cigarettes to an individual smoker should be weighed against the potential harm to the population of increased social acceptability of smoking and use of nicotine, the latter of which has addictive power and untoward effects. As a precaution, electronic nicotine delivery devices should be restricted or banned until more information about their safety is available. If allowed, they should be closely regulated as medicines or tobacco products.”(12) The only medical group that has supported e-cigarettes as a possible smoking cessation device and harm reduction agent is Public Health England (PHE), which has used the statement “95% less harmful than cigarettes” as their core evidence. This figure comes from an article published in the European Addiction Research Journal in 2014.(13)
Proponents of e-cigarettes push the harm reduction angle of vaping over conventional cigarettes. The evidence behind this is controversial. The primary data source used for this argument is the above article endorsed by PHE.(13) It is worthwhile to unpack this particular article, as not only is it used by PHE but also extensively on most vaping sites. Nutt and colleagues describe this study as a “panel of international experts convened by the Independent Scientific Committee on Drugs to develop a multi-criteria decision analysis model of the relative importance of different types of harm related to the use of nicotine-containing products”.(13) The methodology required the committee members to rate 14 harm criteria on a scale of 1 to 100. They then assessed the relative weights for all the criteria to indicate their importance. The article has 29 references, two of which refer to ENDS. So, 12 individuals decided on the harm of various nicotine-containing products with minimal toxicological, epidemiological, or other data. This paper has been presented as based on evidence; it is, at best, an expert opinion. Expert opinion is graded C or level IV - the lowest rank in evidence-based medicine. But PHE and other reporting agencies have claimed this as a “landmark review”.(14) The article ends with a note from the editor acknowledging their awareness that one of the authors has connections with a large tobacco company that produces ENDS but does not see this as a conflict of interest. It seems irregular that an author with potential profit opportunities is not seen as a conflict. This single article has been adopted by the proponents of ENDS and the manufacturers and has been cited repeatedly. The lay public and many health professionals assume the “95% less harmful” is backed by accurate data and is trustworthy. The major flaws of the paper are apparent.
The medical profession has the burden of evidence for ENDS benefits or harm, and studies are becoming more numerous. Randomised trials are now performed to determine whether e-cigarettes are suitable smoking cessation devices. If one reads abstract results only, it appears there is a benefit. However, if one dissects the full results, the main article tells a slightly different story.
In 2019, Hajek and colleagues published a randomized trial of e-cigarettes versus nicotine replacement therapy in the New England Journal of Medicine.(15) This was a randomized trial of 886 participants assigned to either nicotine-replacement therapy (NRT) of their choice for three months or an e-cigarette start kit with one bottle of nicotine (18 mg/ml), allowing them to purchase future e-liquids of their choice. Both groups received at least four weeks of weekly behavioural support. The primary outcome was sustained abstinence for one year, which was biochemically validated. The results reported that at one year, the abstinence rate was 18% in the e-cigarette group compared to 9.9% in the NRT group, with a relative risk of 1.83 (CI 1.30-2.58, p < 0.001). The authors did add that 80% of abstainers were still using e-cigarettes at 1 year vs 9% of NRT abstainers. The conclusion reached was that e-cigarettes are more effective for smoking cessation than NRT. While this result appears to be impressive, what isn’t well highlighted is that at the end of the year, only 3.6% of the e-cigarette users versus 9% of the NRT users had managed to quit nicotine use altogether. The vast majority of the e-cigarette users had just swopped from being conventional cigarette users to e-cigarette users rather than quitting nicotine altogether.
Another study in the NEJM by Auer et al, compared standard smoking cessation counselling versus counselling plus e-cigarettes with a primary outcome at 6 months of biochemically validated continuous abstinence.(16) The participants of both groups were allowed to use NRT if they wanted. They recruited 1246 participants, 622 in the e-cigarette group and 624 in the control group. The e-cigarette arm reported a 28.9% biochemically validated abstinence from tobacco smoking versus 16.3% in the control arm, relative risk 1.77 (95% CI, 1.43 – 2.20). The authors concluded that “the addition of e-cigarettes to standard smoking-cessation counselling resulted in greater abstinence from tobacco use than smoking-cessation counselling alone”. One needs to look at all the results a little closer. In the participant-reported data results, there was no tobacco use in 59.6% of the e-cigarette group versus 38.5% in the control group, but when one looks at no tobacco or e-cigarette use, the picture changes, with 11.2% in the e-cigarette group versus 35.3% in the control group. Patients had yet again demonstrated just a swap from one nicotine product to another rather than cessation of nicotine dependence. These articles are published in high-end journals, and one would therefore assume they have been appropriately vetted. When letters to editors or viewpoints are published, the contradictory nature of results is highlighted, but often, these are not read by the initial readers of the original article.(17)
The medical profession has been fighting and debating with ENDS companies about whether they are or are not safer than traditional cigarettes and could be used as smoking cessation tools. In the interim, ENDS have been freely available in the marketplace and due to very sophisticated advertising, similar to those seen at the height of cigarette advertising, many non-smoking adolescents have been drawn in and have developed nicotine addictions. Preventing youth addiction has always been one of the most important goals of tobacco control programs. Nicotine is known to affect the developing brain adversely. Adolescence is a unique period with characteristic behavioural changes, including increased risk-taking, novelty-seeking, and important peer associations.(18) Adolescents are, therefore, more likely to try new things, and ENDS are primed to appeal to the youth with trendy packages and flavours like Crème Brulé, blue raspberry, bubble gum, and watermelon ice. These flavours seem to be deliberately aimed at the youth. Nicotine exposure in adolescence may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse.(18) Plus, adolescent exposure to nicotine is associated with increased mood and attention problems.(19)
While there may be far less diversity and quantity of toxins in ENDS vapor than in combustible cigarette smoke, ENDS are not “harmless”. A fast-growing collection of data has demonstrated that ENDS aerosol can include heavy metals, volatile organic compounds, and flavoring additives. These can be harmful, especially to the growing lungs. The e-cigarette or vaping use-associated lung injury (VALI) crisis of 2019/20 was caused by a contaminant vitamin E acetate in the diluent in multiple counterfeit, low-cost tetrahydrocannabinol-containing cartridges.(20) As seen with EVALI, a considerable amount of the toxicity data originates from the liquid or “juice” used in ENDS. This includes diacetyl, which is FDA-approved for oral ingestion and can cause bronchiolitis obliterans or “popcorn worker lung” when inhaled.(21) ENDS users are likelier than nonusers to report respiratory symptoms. Compared with never e-cigarette users, past 30-day e-cigarette users reported increased odds of a wheeze (OR 1.81; 95% CI 1.28-2.56), bronchitic symptoms (OR 2.06; 95% CI 1.58- 2.69) and shortness of breath (OR 1.78; 95% CI 1.23-2.57).(22)
There are now multiple studies demonstrating the toxicity and harm that occurs with ENDS.(9,23–25) Ten years from the original Nutt article citing “95% less harmful,” there are mountains of data refuting this. As physicians, we need to decide what we celebrate as a victory. Do we encourage our patients to aim for a life free of nicotine dependence, or are we satisfied with just the possibility of harm reduction and a lifetime continuing to be enslaved to the tobacco industry's profit margin? If we use the latter option, the consequence will be an epidemic of youth nicotine addiction.