Nicotine use creates dependence; however, it is unlikely to be directly responsible for much health harm. Most harm stems from nicotine delivery through smoking (1–3). Although smoking is decreasing in many—though not all—countries worldwide (4), its decline is seen as too slow (e.g., 1). This has led some scientists to ask whether harm reduction approaches may help to accelerate decreased smoking (3, 5). E-cigarettes, e-hookas or pod mods may be used as harm-reducing electronic nicotine delivery systems (ENDS): their use is not harmless but is considerably less harmful than smoking (3, 6–10). We will use the term e-cigarette (EC) as a generic term. Arguments against ECs include that dual use may lead to sustained smoking among smokers who would otherwise have quit, that EC use may re-normalise smoking-like behaviour (inhaling) in public, and finally that ECs may divert smokers who are motivated to quit away from evidence-based smoking cessation treatments (6). ECs may also seem attractive to young people and lead to nicotine use which would not have occurred otherwise and subsequently to smoking (gateway effect: 11). A recent review of the evidence (12) identified seven systematic meta-analytical reviews, of which two found a positive effect (13, 14), four were inconclusive (15–18) and one found a negative effect (19). The present paper argues that the mixed findings on the efficacy or effectiveness of using ECs for reducing or ceasing smoking may be related to the answers to our two research questions. Firstly, is there an overall general population, public health effect? Secondly, is there an effect among a subpopulation of heavy smokers who are highly motivated to quit smoking? The present longitudinal study investigated vaping and its associations with smoking among young men aged around 21.3 years old at baseline, with a follow-up around four years later, and it distinguished between a general “real-world” population perspective and a group of smokers motivated to quit.
One reason for the different conclusions of the meta-analytical reviews may have been the types of studies included. Whereas reviews suggesting beneficial effects were predominantly based on randomised control trials (RCTs) (3), the sole review suggesting negative effects (19) included numerous observational studies, and even cross-sectional studies, which could not separate cause and effect. The review by Villanti et al. (20) set stricter criteria for studies on using ECs for reducing or quitting smoking. Only four studies fitted those criteria (21–24). All four were randomized controlled trials (RCT) and found, at best, small, but usually non-significant favourable effects for using nicotine ECs.
Commentaries on the paper by Villanti et al. (20) criticised its focus on RCTs and its assessment limited to EC users who were only motivated by smoking cessation (25, 26). To evaluate the potential impact of promoting ECs as a public health approach, there is a need to investigate how ECs are used in real-world clinical settings or, even more significantly, in the general population. Strict inclusion criteria limiting investigations to smokers who desperately want to quit (and excluding others) do not reflect real-world EC use in the general population. Many vapers do so for other reasons, e.g. costs, the ability to use it where tobacco is banned or to maintain a similar habit as part of daily routines. Similarly, strict inclusion criteria as regards certain parameters of EC use, such as frequency of use, type, dose or duration, do not reflect real-world use either (26). Daily vaping and the use of more recent innovations in EC models (e.g. tank, mod and pod systems), which provide more effective nicotine delivery and therefore are sufficiently appealing to smokers, have shown promising effects in RCTs (for reviews see 3, 20, 27–29) but do not necessarily correspond to real-world use at the general population level (see 30).
Although RCTs are commonly regarded as the strongest epidemiological designs, they do have inherent drawbacks. Simply participating in an experiment and having greater interaction with a therapist may increase motivation for the treatment, belief that the treatment is important and the behaviour typical of good subjects (31–33). Participants’ informed consent may be perceived as binding contracts which they do not want to break (34), and the inclusion and exclusion criteria of RCTs commonly lead to highly selective groups of participants. This does not reflect the groups of patients found in standard clinical settings (35) and even less so in the general population.
Longitudinal studies in the general population are particularly important when it comes to regulating ECs (e.g. maximum nicotine concentrations, taxes). Even critics of ECs generally admit that their use can result in decreased smoking and cessation for some smokers. However, whether the overall effect of EC use is harmful or beneficial depends on its predominant type of use in the general population. Those who regard EC use as more harmful than beneficial promote strong regulation (e.g. 11, 36, 37). Those who see its potentially beneficial effects, through decreased smoking and cessation, promote less regulation than for conventional cigarettes (CCs) (2, 12, 29).
Two of the recent systematic reviews (14, 15), deemed to be of high quality (38), included three general population studies. Brose et al. (39) found that after one year, daily EC users were more likely than non-users to have attempted to stop smoking (but not to have stopped) and to have reduced their number of cigarettes smoked by 50%. No effects were found for occasional EC users, and only about one fourth of all EC users were daily users. Al-Delaimy et al. (40) found that, after one year, ever- EC users had made a non-significant greater number of attempts to quit, but they were significantly less likely to quit and less likely to have decreased cigarette use. Manzoli et al. (41) compared formerly-smoking EC users with tobacco smokers and dual users, and they found that EC users were significantly more likely to have persisted in their tobacco abstinence; however, dual users were not more likely to become tobacco abstainers, and they also did not reduce tobacco use.
There are recent longitudinal studies on the general population. Many looked at the potential for ECs to introduce young people to smoking (42–44), confirming reviews that ECs expanded the nicotine market by attracting young people who may later use CCs (11, 45). A general population study of adults (18+) in the USA by Benharmina et al. (38) showed that ECs may increase the likelihood of tobacco abstinence among those attempting to quit. However, the vast majority relapsed to cigarette smoking, and those who did continued to use ECs in addition to CCs with no reduction of CC use. Findings from the same study (46) showed that at least high frequency of EC use at follow-up (but no use at baseline) may be associated with a reduction in CCs smoked. A general population study in France examined daily smokers and former daily smokers (47). After two years, regular (daily) vapers had reduced their daily CC use by about 1.7 cigarettes per day more than non-vapers. They also had a higher likelihood of quitting smoking. However, former smokers were more likely to relapse to CC smoking if they were vapers. Daily users, but not occasional users, were also shown to reach higher abstinence compared with non-vapers (48).
The present study examined EC use and its associations with smoking cessation, attempts to quit and CC use among a cohort of young men aged around 21.5 years old at baseline and continuing for 4 years of follow-up. It compared never-smokers, former smokers and persistent smokers in that population as a whole. This paper presents sensitivity analyses of the EC use modes assumed to have the most advantageous effects on smoking cessation (e.g. daily use, use of newer generations of ECs, use of nicotine liquids, and being motivated to reduce or cease CC smoking). The study was the continuation of an earlier one (49) which measured vaping at the baseline only.