To Vape or Not to Vape
A Controversy Erupts Over the Benefits and Harms of E-cigarettes
It is rare that one study, no matter how well executed and how convincing the findings, is sufficient to impact healthcare and public health policy. The mantra of science is that no study should be accepted as true until it is replicated at least once, if not more often.
But a recent study published in the New England Journal of Medicine has provoked widespread comment and debate even before it is replicated. In the January 30, 2019 edition of the journal, investigators from the U.K. reported on a study in which they randomized 886 adult cigarette smokers to receive either nicotine replacement products (e.g. patches, gum, lozenges) or nicotine-filled e-cigarettes. Both groups received behavioral support to stop smoking and the study subjects were followed for a year.
The study was designed to answer an important health question. Proponents of e-cigarettes have long argued that they can be an important aid for people who want to stop smoking cigarettes. Given that smoking remains the leading cause of preventable death in the world, killing seven million people annually, even small decreases in the number of people who smoke can have enormous personal and public health benefits. Still, significant doubt existed about whether e-cigarettes are any better than already existing methods of smoking cessation and, given fears of potential harms from them (see below), it has been unclear what place e-cigarettes have in promoting abstinence from smoking.
The rigorously conducted UK study, then, comes at an important junction in understanding the role of e-cigarettes. The study results showed that 18% of those assigned to the e-cigarette group were abstinent from cigarette smoking, compared to 9.9% who received nicotine replacement products, a statistically significant difference. Adverse side effects were not serious in either group. The study seems to unequivocally demonstrate that e-cigarettes are superior to nicotine patches and gum for helping people quit smoking.
The study naturally garnered a lot of media attention and was cheered by people who have long argued that e-cigarettes should be seen as having a major health benefit. Reading the media reports and the study abstract, it would be easy to conclude that the issue is settled and that smokers should be encouraged to purchase refillable e-cigarettes and bottles of nicotine liquid. Naturally, another study reaching the same conclusion would be reassuring, but given that the New England Journal of Medicine study found no significant adverse side effects from e-cigarettes and the urgency to stop smoking, it might at first seem to make sense that doctors and public health officials should begin to recommend them along with behavioral support to people who want to stop smoking.
An Epidemic Declared
But the study did not, in fact, win over the many health experts who see e-cigarettes as a major public health threat. Only a month before the New England Journal of Medicine e-cigarette study was published, the U.S. Surgeon General Jerome Adams issued an advisory “stressing the importance of protecting children from a lifetime of nicotine addiction and associated health risks by immediately addressing the epidemic of youth e-cigarette use”. Calling vaping, as e-cigarette smoking is commonly referred to, an “epidemic” certainly seems at odds with viewing it as a positive health intervention.
The basis for concerns about vaping stems from what are indeed skyrocketing rates among American youth. In just the one year between 2017 and 2018, the CDC reports that e-cigarette use increased from 11.7% to 20.8% of high school students and from 3.35 to 4.9% of middle school students. That almost five million students use e-cigarettes is a concern if one or both of the following claims about e-cigarettes is true:
- The high concentrations of nicotine in e-cigarettes is itself harmful to health.
- Vaping increases the risk that a young person will begin smoking cigarettes.
The CDC seems certain that the first of these statements is true. In its most recent advisory it states that “Youth nicotine use can lead to addiction and can harm the developing brain, impacting learning, memory, and attention”. An editorial accompanying the e-cigarette study in the New England Journal of Medicine stated that “e-cigarette vapor contains many toxins and exerts potentially adverse biologic effects on human cells in vitro or in animal models, although toxin levels and biologic effects are generally lower than those of tobacco smoke”.
As for the second statement, a recent study did in fact find evidence that “e-cigarettes represent a catalyst for cigarette initiation among youths”. Another accompanying editorial to the New England Journal of Medicine study warned that “Even if these adolescents do not switch to regular cigarettes, creation of a large cohort of nicotine-addicted adults has consequences beyond the adverse physiological effects of nicotine. Since nicotine is a gateway drug that lowers the threshold for addiction to other agents, the use of e-cigarettes could help spawn even more opioid addiction”.
The FDA launched a campaign to limit sales of e-cigarettes to youth last November and is especially concerned about flavored varieties of nicotine used in e-cigarettes, which may have special appeal for children and adolescents. Altria, the manufacturer of the most popular vaping product, Juul, has insisted it opposes the use of its e-cigarette products by youth, but FDA commissioner Scott Gottlieb has been unimpressed with Altria’s efforts and recently threatened to ban the sale of e-cigarettes in stores if rates of their use among adolescents don’t drop more rapidly. Altria (formerly the Philip Morris Companies) is also a major manufacturer of cigarettes. Any connection to a tobacco company naturally makes us wary, given the industry’s years of obfuscating the real harms of cigarette smoking.
Is There a Role for E-Cigarettes?
The data presented by the study comparing e-cigarettes to nicotine replacement products are fairly easy to grasp: the e-cigarette group had a higher cigarette quit rate than the nicotine replacement product group. The data linking nicotine to biological harm and vaping to increased risk of initiating cigarette smoking are far more complex. The case that nicotine is a health harm rests largely on studies in test tubes and animals and small studies in humans. The link between e-cigarettes and cigarette smoking initiation involves large epidemiological studies. It is not always easy to extrapolate from animal studies to human health effects and epidemiological studies are prone to uncontrolled factors that limit definitive conclusions.
Yet although the case that e-cigarettes are harmful may be more complicated for us to grasp than the evidence that it helps people stop smoking, that does not mean we can dismiss it. We are right to be wary of a product now used by millions of children that contains an addicting substance that may be harmful.
We desperately need to reduce the rates of cigarette smoking around the world. One thing not to be overlooked in evaluating the New England Journal of Medicine study is that we already have interventions that offer rates of abstinence that rival what was seen with e-cigarettes in the study. As Belinda Borrelli and George O’Connor noted in their accompanying editorial, adding the FDA-approved medication bupropion to nicotine replacement products produces quit rates of 20% at one year, almost exactly the rate observed with e-cigarettes. And perhaps even more effective is the FDA-approved medication varenicline (brand name, Chantix), which yielded an abstinence rate of 26% at 24 weeks. It is important to remember, however, that to our knowledge there are no studies that directly compare e-cigarettes to either either bupropion or verenicline for cigarette smoking cessation. Caution is always important when comparing rates from different studies (or absolute rates) as opposed to direct comparisons (or relative rates).
Varenicline has been burdened with fears that it can cause suicidal ideation, leading the FDA to issue a black box warning about the connection in 2009. A subsequent large study did not find evidence of increased suicidal behavior in people taking varenicline compared to other interventions and the black box warning was removed in 2016. It is also clear that the risk of dying from cigarette smoking is far higher than any possible risk of suicidal behavior induced by varenicline; it should be prescribed more often to people who cannot quit smoking by other methods.
It might seem an ideal solution to make e-cigarettes available to adults who want to stop smoking while at the same time making them unavailable to youth. Once a product is on the market, however, it is hard to prevent one group from using it while encouraging others. For now, the safest course may be to continue to make every effort possible to keep adolescents from vaping and to recognize that prescribing drugs like bupropion and varenicline are probably the best way to help smokers who cannot quit with nicotine replacement products on their own. Hopefully, we will eventually know for sure if there are health risks to long-term vaping, but until we do the New England Journal of Medicine study, although well done and welcome, does not mitigate safety concerns.