E-Cigarettes and Cardiopulmonary Health

Review for Clinicians

Evan W. Neczypor, BS; Matthew J. Mears, BS; Arunava Ghosh, PhD; M. Flori Sassano, PhD; Richard J. Gumina, MD, PhD; Loren E. Wold, PhD; Robert Tarran, PhD


Circulation. 2022;145(1):219-232. 

In This Article

Abstract and Introduction


Electronic cigarettes (e-cigarettes) are battery powered electronic nicotine delivery systems that use a propylene glycol/vegetable glycerin base to deliver vaporized nicotine and flavorings to the body. E-cigarettes became commercially available without evidence regarding their risks, long-term safety, or utility in smoking cessation. Recent clinical trials suggest that e-cigarette use with counseling may be effective in reducing cigarette use but not nicotine dependence. However, meta-analyses of observational studies demonstrate that e-cigarette use is not associated with smoking cessation. Cardiovascular studies reported sympathetic activation, vascular stiffening, and endothelial dysfunction, which are associated with adverse cardiovascular events. The majority of pulmonary clinical trials in e-cigarette users included standard spirometry as the primary outcome measure, reporting no change in lung function. However, studies reported increased biomarkers of pulmonary disease in e-cigarette users. These studies were conducted in adults, but >30% of high school–age adolescents reported e-cigarette use. The effects of e-cigarette use on cardiopulmonary endpoints in adolescents and young adults remain unstudied. Because of adverse clinical findings and associations between e-cigarette use and increased incidence of respiratory diseases in people who have never smoked, large longitudinal studies are needed to understand the risk profile of e-cigarettes. Consistent with the Centers for Disease Control and Prevention recommendations, clinicians should monitor the health risks of e-cigarette use, discourage nonsmokers and adolescents from using e-cigarettes, and discourage smokers from engaging in dual use without cigarette reduction or cessation.


Electronic cigarettes (e-cigarettes) are a relatively new and developing electronic nicotine delivery system that became commercially available in 2004. The long-term cardiopulmonary effects of e-cigarettes remain poorly understood. Maintaining up-to-date knowledge on e-cigarettes is a challenge for clinicians, especially because e-cigarettes continue to change in engineering design and chemical composition and are often released commercially without clinical safety or smoking cessation efficacy data. E-cigarettes are battery-powered heating elements connected to a tank or reservoir that contains a mixture of nicotine, flavors, and other chemicals dissolved in a propylene glycol/vegetable glycerin vehicle of varying ratios (Figure 1).[1] The first 2 generations of e-cigarettes were inefficient at increasing plasma nicotine compared with combustible tobacco products. In contrast, high-powered third-generation devices achieved similar plasma nicotine levels and pharmacokinetics as tobacco cigarettes.[2] Fourth-generation e-cigarette devices (eg, JUUL, Puff Bar) switched from freebase nicotine to nicotine salt and benzoic acid.[3] Previous research has indicated that less e-liquid is consumed when using devices with higher nicotine content.[2] Therefore, more efficient nicotine delivery could reduce overall exposure to e-cigarette aerosol; however, this has not been directly studied in fourth-generation devices relative to older models. Fourth-generation e-cigarette devices are readily available in both rechargeable and disposable forms with limited regulation. The effect of e-cigarettes on cardiopulmonary health only beginning to be understood.

Figure 1.

First- to fourth-generation e-cigarette devices. From left to right: first-generation ("cig a-likes"), second-generation ("vape pens"), third-generation ("tanks" and "mods"), and fourth-generation ("pod mods") e-cigarette devices. First- and second-generation e-cigarette devices were tubular and inefficient in nicotine delivery when compared with combustible tobacco products. Third-generation devices were customizable and contained larger tanks with larger, higher-voltage batteries and were comparable to conventional cigarettes in nicotine delivery efficiency. Fourth-generation (eg, JUUL, Puff Bar) devices have smaller tanks (pods) and batteries with decreased nicotine delivery efficiency. However, fourth-generation e-cigarettes compensated for lost efficiency by switching from freebase nicotine (used in first-third generation devices) to higher concentrations of nicotine salt, along with benzoic acid. These devices are available in reusable (left) and disposable (right) forms.