Not simply the lesser of two evils

Electronic cigarettes (e-cigs) are nicotine delivery devices consisting of a battery-powered atomizer to vaporize cartridge fluid containing nicotine, flavorings, and vehicle mixture made of vegetable glycerin (VG) and propylene glycol (PG). E-cigs were originally developed to aid smoking cessation based on the rationale that vapors from nicotinic formulations with few-known ingredients may prove safer alternatives to conventional tobacco smoke. However, such rationale was not backed by scientific evidence that e-cig vapors are devoid of harmful chemicals, and it should be noted that the concept of an idealized nicotine delivery device has been long sought by the tobacco industry to introduce and maintain addiction potential (9). Consequent promotion of e-cigs as healthier tobacco alternatives, smoking cessation, and socially acceptable products has caused a rapid increase in their consumer acceptance among both current smokers as well as previously nonsmoking individuals. Most alarmingly, poor regulatory oversight and wider availability of e-cigs with variety of flavors has popularized e-cig use among highly vulnerable teenagers and young adolescents. In the United States, despite the Food and Drug Administration (FDA) asserting the constitutional authority to regulate e-cigs and other emerging tobacco products, effective regulatory policy has been slow to emerge in response to the emerging public health threat. Rampant increase in the number of product designs and e-liquid formulations has made the scientific evaluation of these products challenging, and the resultant lack of reliable data has thus far hampered FDA and other regulatory agencies. Meanwhile, public health and scientific community are divided between two competing perceptions of e-cigs as a reliable solution to reduce nicotine dependence or as a new unchecked contributor to the evolving tobacco epidemic.

The American Journal of Physiology-Lung Cellular and Molecular Physiology has responded to this crisis with a call for papers addressing critical questions regarding potential toxic effects of e-cigs including the underlying mechanisms and implications for long-term cardiopulmonary health. This effort has resulted in publication of several highly cited original research articles adding to the growing body of literature on the harmful effects of e-cigs (15, 21–23). Chun et al. (6) summarized these and other studies in an aptly titled review, “Pulmonary toxicity of e-cigarettes.” For this report, relevant literature was reviewed from studies older than 20 years on occasion, but not surprisingly, most of the discussion is based on recent literature related to the evolution of e-cig devices, their design, e-liquid composition, patterns of use, and observed biological effects. The major strengths of this review are the breadth of clinical and biological studies being considered and comprehensive summaries of findings from in vitro, in vivo, and human study regarding the pulmonary consequences of e-cigs. The authors made a commendable effort in highlighting the limitations of many studies they quoted and, at the end, list out several important considerations for designing future studies with e-cigs to address unmet research needs. Like all reviews, there are limitations to the breadth of particular aspects and depth of detail that can be incorporated within one report.

In a letter to the editor, Caruso et al. (4) question the review by Chun et al. (6) for its focus on pulmonary toxicity, the stated objective of the review; the lack of emphasis on two flawed reports concluding improved respiratory status among patients who transitioned from traditional cigarettes to e-cigs; and for not including a discussion on the benefits of e-cig on smoking cessation (4, 8). A large part of their criticism centered on the disagreement about the suitability of basic laboratory research for gathering clinical-relevant knowledge, concluding that in vitro and in vivo models of vapor exposure are irrelevant to interpret the impact of e-cigs on human health because of differences in exposure type and the nature of acute exposure studies (13); further, they find the exclusive discussion of e-cig toxicity isolated from smoke cessation as incomplete. In turn, they quote additional clinical studies that concluded e-cig use promotes smoking cessation (3, 8), although we note that details on how e-cigs improved long-term health of its users is not yet available.

Chun et al. (7) of the original review strongly counter this criticism in a response letter by clearly stating the limitations of the clinical studies quoted by Caruso et al.; in particular, the lack of nonsmoking controls or cohorts with equal overall tobacco product exposure that undermine the conclusions that supported e-cigs as effective cessation products. They also address what we perceive as unjustified criticism of laboratory research on e-cig impact by highlighting the important contributions made by basic research to the advancement of respiratory medicine and health policy. Chun et al. remind us the historic mistakes from the earlier decades when both medical community as well as the regulatory bodies failed to address the threat posed by tobacco epidemic. While numerous scientific studies from 1950s and 1960s reported the causal link between tobacco use and the incidence of cancers and cardiopulmonary diseases (10, 20), advocacy and litigation by tobacco companies mitigated broad utilization of such knowledge in a timely manner. As a result, any continued e-cig use without adequate understanding of the potential harmful effects on human health may prove another public health misadventure, led on by excessive exuberance regarding the perceived safety of these poorly understood devices. These concerns are reminiscent of the introduction and marketing of low-tar cigarettes by tobacco manufacturers with misleading labels such as “light” and “ultra light” that suggested reduced harm and that ultimately proved to be a deterrent to smoking cessation (12, 26). We maintain these same faulty perceptions contribute to the rapid uptake of these devices (16), even among nonsmokers (19) and adolescents (24), leading to addiction and traditional cigarette use later in life (1).

As both sets of authors attest, smoking cessation can improve health and is the most desired outcome relating to tobacco epidemic. Yet, it is important to note that despite historic reductions in tobacco use in Western countries (14), the incidence of lung cancer and chronic obstructive lung disease (COPD) continues to increase (2, 11, 25), emphasizing decades-long pathogenic processes involved in tobacco harm. As a result, it is important to conduct basic and clinical studies to gain the necessary data to project long-term implications of e-cigs. Toward this important goal, we need more focused literature on the toxicity of e-cig on individual organ systems and predictive animal models as a whole and should not be deterred or delayed by disagreements regarding the perceived value of the effectiveness of e-cigs as cessation agents. It is worth noting that recent work has shown that e-cigs have led to the use of more nicotine products and not fewer (1, 19, 24). Since there is no disagreement that nicotine is harmful, the production (5), availability, and administration of nicotine products need to be effectively regulated to preserve public health. Hence, the standards that currently apply to all other cessation products including multiphase clinical testing should be applied to e-cigs.

It is our opinion that nothing short of breathing clean healthy air will ensure the most effective harm reduction from smoking tobacco: inhalation of anything less than clean air is sure to cause more harm than good. Paraphrasing the words of Ralph Nader, a noted advocate and author, when you choose lesser of two evils, you will always have evil, and you will always have less.

GRANTS

This work was supported by National Institutes of Health Grants P30-DK-072482 (to S. M. Rowe) and 1R01-HL-105487 (to S. M. Rowe), Cystic Fibrosis Foundation Grant CFF R262 (to S. M. Rowe), and Flight Attendants Medical Research Association Grant YFA130008 (to S. V. Raju).

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

S.R. and S.M.R. drafted, edited, revised, and approved final version of manuscript.