A new study that suggests that teens who try electronic (e)-cigarettes are more likely to smoke has been hailed as "the strongest evidence to date that e-cigarettes might pose a health hazard by encouraging adolescents to start smoking conventional tobacco products."

The comment comes from an editorial by Nancy A. Rigotti, MD, from the Massachusetts General Hospital and Harvard Medical School in Boston, published in the August 18 issue of JAMA. It accompanies a study on the use of e-cigarettes by adolescents.

E-cigarette devices, which deliver inhaled aerosol usually containing nicotine, are becoming increasingly popular, particularly among adolescents who report never having smoked combustible tobacco, according to the study authors, led by Adam Leventhal, PhD, from the University of Southern California Keck School of Medicine in Los Angeles.

The team set out to determine whether teens in their first year of high school, a period when risky behaviors often start, are prone to start smoking cigarettes once they have tried e-cigarettes.

Their study involved 2530 students from 10 public high schools in Los Angeles who, at study entry in the fall of 2013, reported never having used combustible tobacco.

The mean age of the students was 14.1 years, and all were starting the ninth grade.

The students were assessed 6 months after study enrollment (in the spring of 2014), when they were still in the ninth grade, and then 12 months after enrollment (in the fall of 2014), when they were in the tenth grade.

At each time point, the students completed self-report surveys on the use of any combustible tobacco products.

The researchers found that the 222 e-cigarette users at baseline were more likely than the 2308 never-users to report the use of any combustible tobacco product in the previous 6 months at 6-month follow-up (30.7% vs 8.1%) and at 12-month follow-up (25.2% vs 9.3%).

In an analysis adjusted for sociodemographic, environmental, and intrapersonal risk factors for smoking, e-cigarette use at baseline was associated with a greater likelihood of use of any combustible tobacco product averaged across both follow-up periods (odds ratio [OR], 2.73; 95% confidence interval [CI], 2.00 - 3.73).

In addition, e-cigarette users at baseline were more likely than never-users to be using at least one combustible tobacco product at both follow-up assessments. For combustible cigarettes, the OR was 2.65 (95% CI, 1.73 - 4.05); for cigars, the OR was 4.85 (95% CI, 3.38 - 6.96); and for hookah, the OR was 3.25 (95% CI, 2.29 - 4.62).

Vulnerable, and Susceptible to Experimentation

"These data provide new evidence that e-cigarette use is prospectively associated with increased risk of combustible tobacco use initiation during early adolescence," the authors write.

"The neurodevelopmental and social backdrop of early adolescence may promote risk-taking behavior, and neural plasticity may sensitize the adolescent brain to the effects of nicotine. Hence, adolescent never-smokers exposed to nicotine-rich e-cigarette aerosols and the pleasant sensations associated with vaping could be more liable to experiment with other nicotine-containing products, including combustible tobacco," they note.

However, they point out that because their study is observational, and one of the first to address this issue, "inferences regarding whether this association is or is not causal cannot yet be made."

The strengths of the study, they report, are the demographically diverse sample, the repeated measures of tobacco use, the exclusion of ever-smokers at baseline, the high follow-up rate, the comprehensive assessment of multiple combustible tobacco products, and the statistical control for important covariates.

Limitations of the study are that e-cigarette use was measured only as any use, and that characteristics of the e-cigarettes, such as nicotine strength and flavor, were not assessed.

"The age period focused on in this study captured an important, but brief window of susceptibility. In this and other samples, youths commonly initiated use of combustible tobacco prior to ninth grade and e-cigarette use after ninth grade, suggesting that investigating other ages is warranted," the authors add.

"Tantalizing" Prospects for E-Cigarettes

In her editorial, Dr Rigotti notes that this study "represents an important new contribution to the much-needed evidence base." She also calls for more research to understand the balance of benefits and risks of e-cigarettes.

Although both normal and e-cigarettes deliver nicotine, the addictive agent in tobacco, the electronic devices do not expose the user to the tobacco-smoke constituents that can cause tobacco-related diseases, she points out.

"E-cigarettes therefore offer the tantalizing prospect that they could reduce the harms of conventional tobacco use, the leading cause of preventable death and disability in the United States and worldwide," Dr Rigotti comments.

However, there are three principal public health concerns about e-cigarettes, she notes. First is their potential to renormalize cigarette use if they are permitted in venues where cigarettes are banned. Second is their potential appeal to nonsmokers, especially children and adolescents. Third is the possible health risks related to exposure to e-cigarette constituents, such as flavorings and propylene glycol, or to e-cigarette contaminants.

The Los Angeles study addressed the second point — the appeal of these products to youngsters. But, Dr Rigotti points out, "regardless of whether e-cigarettes are a gateway to tobacco product initiation, there is no reason for adolescents to use a product for which the hypothesized public health benefit is harm reduction for adult smokers."

"However, there is ample evidence that e-cigarettes are marketed in ways that appeal to children and adolescents," she notes, adding that "prompt, effective action is needed to protect youth and reduce the demand for e-cigarettes by nonsmokers of all ages."

"A rational approach is to extend to e-cigarettes the same sales, marketing, and use restrictions that apply to combustible cigarettes," she explains, and notes that the US Food and Drug Administration (FDA) has already taken steps in this direction.

The proposed FDA regulations for e-cigarettes "set the age of 18 years as the minimum age of sale, require health warnings on e-cigarettes, and open the door for future product standards. The FDA should move swiftly to finalize this rule, which to date has not been issued and is overdue," Dr Rigotti writes.

E-Cig Propellants Produce Known Carcinogens

In a related viewpoint, Andrew Y. Chang, MD, and Michele Barry, MD, from the Stanford University School of Medicine in California, discuss the health implications of e-cigarettes around the world.

Advocates of e-cigarettes, also known as electronic nicotine delivery systems (ENDS), claim that they offer significant harm reduction because they do not create the carcinogens found in conventional cigarettes.

As a result of these claims, the use of e-cigarettes has increased globally. A 2014 World Health Organization survey suggested that more than half of the world's population lives in countries where such products are sold, Drs Chang and Barry point out.

"The growing market was valued at an estimated US$3 billion in 2013, with projections estimated to reach $10 billion by 2017," they note.

And e-cigarettes are available not only in wealthy countries, but in low- and middle-income countries because the devices can be made inexpensively.

The assertion by supporters — that the products reduce harm and serve as a smoking-cessation aid and are, therefore, potentially superior to existing conventional tobacco products — is "problematic for several reasons," the pair states.

"First, data supporting the effectiveness of e-cigarettes at helping smokers quit are lacking, with randomized clinical trials finding no significant difference in tobacco quit rates between patients who used ENDS with nicotine and those who used placebo," they explain.

"Second, the argument that ENDS manufacturers sell e-cigarettes solely as a smoking-cessation tool is not supported by their marketing, which often appears geared toward minors and never-smokers. Nicotine cartridges are sold in a variety of youth-appealing flavors, such as fruit, candy, and cola," they write.

The ENDS manufacturers have falsely promoted their products as a "safe alternative" to smoking because e-cigarettes do not rely on high-temperature combustion like conventional cigarettes, Drs Chang and Barry write.

"Emerging data, however, demonstrate that the propellants used in these devices, such as propylene glycol or glycerines, decompose into known carcinogens, such as formaldehyde and acetone, when aerosolized," they point out.

The tobacco industry has been turning its attention to e-cigarettes recently, "possibly in response to declining sales of conventional cigarettes," they note.

The study was supported by the National Institutes of Health. Dr Rigotti reports financial relationships with UpToDate, Pfizer, and Arena Pharmaceuticals. Dr Leventhal, Dr Chang, and Dr Barry have disclosed no relevant financial relationships.

JAMA. 2015;314:663-664, 673-674, 700-707. Viewpoint, Editorial, Abstract