E-cigarettes for smoking reduction: A piece of the public health puzzle

Since the introduction of electronic cigarettes (e-cigarettes) into the tobacco marketplace, their role in reducing the population health burden of cigarette smoking has been frequently discussed. Data from randomized controlled trials (RCTs) showed that, compared to conventional smoking cessation therapy, offering free e-cigarettes is positively associated with smoking cessation for six to twelve months.¹ However, data from observational studies in the naturalistic environment show that under most conditions, e-cigarette use is inversely associated with smoking cessation.¹ In their Lancet Respiratory Medicine paper, Cobb and colleagues report an RCT conducted to answer a different question: is the nicotine concentration in e-cigarettes associated with reduction in smoking (measured as cigarette per day, CPD) and in exposure to tobacco-specific carcinogens such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A key finding was that participants randomized to using high-nicotine (36 mg/ml) e-cigarettes had lower urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a metabolite of NNK) levels. The study was conducted with technical skill and the findings have several implications.

First, one should be cautious about interpreting the finding as evidence that e-cigarettes are an effective smoking reduction tool appropriate for general distribution. Participants in this study were given free products with different nicotine concentrations and made ten clinic visits with supports from clinic staff over a 24-week period. No e-cigarettes currently sold in the marketplace offer the same levels of support. Thus, observational studies are needed to determine whether smokers who use high nicotine-concentration e-cigarettes outside in the naturalistic environment receive comparable benefits from e-cigarette use.

Second, reduction in urinary NNAL does not always translate into the reduction in overall health risks. As well as causing cancer, smoking causes cardiovascular diseases (CVDs), which are more prevalent and therefore have a higher smoking-related population-attributable deaths.² Furthermore, smoking reduction does not always result in meaningful reductions in CVD biomarkers compared with the reduction from smoking cessation.³ Previous cohort and case-control studies not involving e-cigarettes showed that ≥50% reduction in CPD (comparable to participants in the 36 mg/ml condition) was associated with lower lung cancer risk compared with persons who sustained heavy smoking; but this was not associated with significant reduction in CVD incidence and mortality and all-cause mortality.⁴ Moreover, even smoking 6–10 cigarettes per month was still associated with higher all-cause mortality risk compared with never smoking in the US population.⁵ Moreover, epidemiological studies have shown that e-cigarette use is associated with a higher risk of respiratory diseases in general-population samples⁶ and laboratory studies have linked exposure to e-cigarette aerosol to biological processes that pose risks of CVDs and pulmonary illnesses.^6,7 Therefore, the overall health benefit of smoking reduction through e-cigarettes remains unclear.

Third, currently there is no national standard for e-cigarette nicotine concentration in the US, whereas the European Union’s Tobacco Products Directive only allows a maximum concentration of 20 mg/ml. Data from Cobb and colleagues suggest that high nicotine concentration may help reduce smokers’ exposure to harmful constituents in cigarettes. However, high nicotine concentration may increase the risk of nicotine addiction in a new generation of users, especially among youth and young adults. Moreover, e-cigarettes have been associated with smoking relapse among former smokers.⁸ To maximize public health benefits, high nicotine-concentration e-cigarettes might be regulated as medical devices and made available through prescription only for use in smoking cessation programs with behavioral support, while low nicotine-concentration e-cigarettes would be removed from the market as consumer products.

Fourth, smoking-related morbidity and mortality vary by race/ethnicity. For example, at 10 CPD, African-American and Native-Hawaiian smokers have higher estimated rates of lung cancer than European-American smokers.⁹ Consequently, it is unclear whether smoking reduction would be associated with equal reduction in lung cancer risk across races/ethnicities. Moreover, non-Hispanic Blacks, American Indians, and Alaskan Natives are less likely to use e-cigarettes for smoking cessation than non-Hispanic Whites.¹⁰ Therefore, it remains unclear if high nicotine-concentration e-cigarettes would reduce lung cancer and other tobacco-related health outcomes equally across subpopulations.

In conclusion, the role of e-cigarettes in reducing tobacco-related morbidity and mortality and their disparities in the population remains unclear. Cobb and colleagues conducted a carefully designed RCT showing that high nicotine concentration may be a potentially important product specification linked to reduced urinary NNAL. To truly evaluate health impact of smoking reduction through e-cigarettes, future research needs to investigate how such behavior relates to cancer, CVD, and other diseases and mortality in the general and high-risk populations. Future studies are needed to understand how to regulate e-cigarettes (e.g., as prescription-based medical devices use in smoking cessation programs) to translate Cobb and colleagues’ finding outside of controlled environments. Findings from future studies, together with those from Cobb and colleagues, will provide the missing pieces of the puzzle to strengthen the evidence for policy making to promote public health. It should always be emphasized that complete smoking cessation provides the most health benefits to smokers and the population.