Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review

Complete tobacco cessation is the best outcome for smokers. However, the powerful addictive properties of nicotine and the ritualistic behavior of smoking create a huge hurdle, even for those with a strong desire to quit. Until recently, smokers were left with just two alternatives: either quit or suffer the harmful consequences of continued smoking. This gloomy scenario has allowed the smoking pandemic to escalate, with nearly 6 million deaths annually and a predicted death toll of 1 billion within the 21st century [World Health Organization, 2013]. But a third choice, involving the use of alternative and much safer sources of nicotine with the goal to reduce smoking-related diseases is now available: tobacco harm reduction (THR) [Rodu and Godshall, 2006].

Electronic cigarettes (ECs) are the newest and most promising products for THR [Polosa et al. 2013b]. They are electrically-driven devices consisting of the battery part (usually a lithium battery), and an atomizer where liquid is stored and is aerosolized by applying energy and generating heat to a resistance encircling a wick. The liquid used mainly consists of propylene glycol, glycerol, distilled water, flavorings (that may or may not be approved for food use) and nicotine. Consumers (commonly called ‘vapers’) may choose from several nicotine strengths, including non-nicotine liquids, and a countless list of flavors; this assortment is a characteristic feature that distinguishes ECs from any other THR products. Since their invention in 2003, there has been constant innovation and development of more efficient and appealing products. Currently, there are mainly three types of devices available [Dawkins, 2013], depicted in Figure 1. (1) First-generation devices, generally mimicking the size and look of regular cigarettes and consisting of small lithium batteries and cartomizers (i.e. cartridges, which are usually prefilled with a liquid that bathes the atomizer). Batteries may be disposable (to be used once only) or rechargeable. (2) Second-generation devices, consisting mainly of higher-capacity lithium batteries and atomizers with the ability to refill them with liquid (sold in separate bottles). In the most recent atomizers you can simply change the atomizer head (resistance and wick) while keeping the body of the atomizer, thus reducing the operating costs. (3) Third-generation devices (also called ‘Mods’, from modifications), consisting of very large-capacity lithium batteries with integrated circuits that allow vapers to change the voltage or power (wattage) delivered to the atomizer. These devices can be combined with either second-generation atomizers or with rebuildable atomizers, where the consumers have the ability to prepare their own setup of resistance and wick.

Awareness and use (vaping) of ECs has increased exponentially in recent years. Data obtained from the HealthStyles survey showed that, in the US, awareness of ECs rose from 40.9-57.9% from 2010 to 2011, with EC use rising from 3.3-6.2% over the same time period [King et al. 2013]. In the United Kingdom, EC use in regular smokers increased from 2.7% in 2010 to 6.7% in 2012 [Dockrell et al. 2013]. Similar findings were obtained from the International Tobacco Control Four-Country Survey [Adkison et al. 2013]. A recent prospective study in Swiss army recruits showed that 12% of smokers who tried ECs progressed to daily use [Douptcheva et al. 2013]. It must be noted that this increase in EC use has occurred despite the concerns raised by public health authorities about the safety and appropriateness of using these products as alternatives to smoking [National Association of Attorneys General, 2013; Food and Drug Administration, 2009; Mayers, 2009].

The popularity of ECs may be due to their ability to deal both with the physical (i.e. nicotine) and the behavioral component of smoking addiction. In particular, sensory stimulation [Rose and Levin, 1991] and simulation of smoking behavior and cigarette manipulation [Hajek et al. 1989] are important determinants of a product’s effectiveness in reducing or completely substituting smoking. These features are generally absent in nicotine replacement therapies (NRTs) and oral medications for nicotine dependence, whereas ECs are unique in that they provide rituals associated with smoking behavior (e.g. hand-tomouth movement, visible ‘smoke’ exhaled) and sensory stimulation associated with it [Farsalinos et al. 2013b]. This explains why these products can be effective in reducing consumption of tobacco smoking [Bullen et al. 2013; Caponnetto et al. 2013b; Polosa et al. 2011] and are efficient as long-term substitutes of conventional cigarettes [Farsalinos et al. 2013b].