The Emerging Phenomenon of Electronic Cigarettes

Pasquale Caponnetto; Davide Campagna; Gabriella Papale; Cristina Russo; Riccardo Polosa

Disclosures

Expert Rev Resp Med. 2012;6(1):63-74. 

In This Article

Electronic Cigarettes: What About the Safety Concerns?

The electronic cigarette concept is currently contested by several health groups, either for pragmatic reasons or because they are opposed to any recreational use of nicotine. One of the main arguments used by this group is that electronic cigarettes may be dangerous.

Detailed toxicology characterization of the components contained in electronic cigarettes' liquid and vapor using gas chromatography mass spectrometry is accumulating rapidly and demonstrates that their primary components are water, PG, glycerin and nicotine.[203] PG has undergone extensive testing and is widely used in a variety of consumer products, including food. It is also approved by US FDA for a variety of pharmaceutical formulations.[204]

In an independent study, Laugesen tested electronic cigarette mist for over 50 priority-listed cigarette smoke toxicants and found none.[205] This report only revealed traces (8.2 ng/g) of tobacco-specific nitrosamines (TSNAs) in the 'high' nicotine cartridge of a Ruyan brand electronic cigarette. However, it must be noted that this amount is equal to the quantity reported to be present in a nicotine medicinal patch. Likewise, laboratory analyses carried out by the FDA failed to find carcinogens and toxic chemicals in most of the products tested with a single exception: traces (˜1%) of diethylene glycol were detected in the liquid of one of the 18 samples, but this represents a nontoxic quantity.[206] The FDA analyses could not detect any harmful chemical in the vapor. Moreover, an independent analysis of the same electronic cigarette products tested by the FDA found no evidence of carcinogenic TSNAs in their aerosol.[207] Recently, Cahn and Siegel have reviewed the evidence regarding the safety of the liquid in electronic cigarettes.[13] TSNAs were reported in two studies, but at trace levels, which are similar to those found in a nicotine patch, and, most importantly, approximately 500–1400-fold lower than TSNA levels measured in regular cigarettes (electronic cigarettes contain only 0.07–0.2% of the TSNAs present in tobacco cigarettes) (Table 1). This is not surprising. Electronic cigarettes deliver a nicotine vapor without the combustion products that are responsible for nearly all of smoking's damaging effects. Temperatures of up to 950°C are generated with each puff of a lit cigarette and some 5000 or so chemicals, many of which are toxic or carcinogenic, are generated during the combustion process.[14] By contrast, electronic cigarettes use the process of vaporization rather than combustion and the low operating temperature of the atomizer (˜50–60°C; ˜5–10% of the temperature of a lit cigarette) suggests that electronic cigarettes, as a class, are unlikely to emit cigarette toxicants in their mist.[205]

Japanese researchers conducted a safety assessment of electronic cigarettes that included 32 smokers and found no abnormal changes in blood pressure, hematological data or blood chemistry and no severe adverse events after 4 weeks of regular use.[15] Our recent clinical safety assessment of one product in 40 smokers showed that mouth and throat irritation and dry cough were commonly reported in the initial few weeks of use, but all appeared to wane spontaneously by the end of the study, after 24 weeks of regular use (Figure 2).[12] These are likely to be secondary to exposure to PG mist generated by the electronic cigarettes's atomizer. PG is a low-toxicity compound widely used as a food additive and in pharmaceutical preparations.[204] Exposure to PG mist may occur from smoke generators in nightclubs, theaters and aviation emergency training, and is known to cause ocular, mouth, throat and upper airway irritation, and cough.[16,17] In all these cases, PG has to be heated in order to generate fog or mist. In our recent study, we have shown that some mouth irritation, throat irritation and dry cough could result from the exposure to PG mist generated by the electronic cigarette's atomizer.[12] However, these symptoms were minor and wane spontaneously with time (Figure 2).

Figure 2.

Adverse events reported by electronic cigarette users who completed all study visits. This illustration was developed based on the findings of the study by Polosa et al. [12].

Dizziness was often reported by participants at the beginning of the study and can be brought about by the hyperventilation associated with the increased puffing time with the electronic cigarette. The substantial reduction in the frequency of dizziness observed by the end of the study may be due to the improved familiarization with the puffing technique. Interestingly, typical withdrawal symptoms were not reported during the course of the study. It is possible that the electronic cigarette, by providing a coping mechanism for conditioned smoking cues, could mitigate withdrawal symptoms associated with smoking reduction and smoking abstinence, as shown for nicotine-free inhalators.[18] In addition, smoking reduction with the brand under investigation led to a substantial decrease in exhaled carbon monoxide levels.[12]

The evidence noted above suggests that electronic cigarettes do not raise serious health concerns and can be seen as a safe way to smoke. Moreover, retailers all over the world have already sold millions of electronic cigarettes, yet there is no evidence that these products have endangered anyone, and no indication that electronic cigarettes are any more of an immediate threat to public health and safety than traditional cigarettes, which are readily available to the public (Figure 3). Although the current data are insufficient to conclude that electronic cigarettes are safe in absolute terms and larger and longer studies are needed to comprehensively assess their safety (particularly in relation to their long-term use), these products appear to be much safer than tobacco cigarettes and comparable in toxicity to conventional nicotine-replacement products. However, it is important to adequately regulate these products so that the safety of consumers is safeguarded.

Figure 3.

Medical infograph. The infograph was developed by the Consumer Advocates for Smoke-free Alternatives Association to provide medical service providers with a comparison of the potential health risks of cigarette smoke with the health risks of vapor. Since electronic cigarette liquid contains only propylene glycol, vegetable glycerin, flavorings and nicotine, the resulting vapor is unlikely to present any more disease risk than medicinal nicotine products – the risk of nicotine addiction. The many more toxic and carcinogenic ingredients in tobacco smoke are linked to numerous health problems.
COPD: Chronic obstructive pulmonary disease.
Adapted with permission from the Consumer Advocates for Smoke-free Alternatives Association (CASAA).

Detractors of the electronic cigarette concept also claim that nicotine is harmful. This has generated great confusion and fierce debate. Nicotine fulfils all the criteria of an addictive agent, including psychoactive effects, drug-reinforced behavior, compulsive use, relapse after abstinence, physical dependence and tolerance. Nicotine stimulates specialized receptors in the brain that produce both euphoric and sedative effects.[19] Individuals who have emotional dysfunctions or attention deficits are more likely to start smoking and less likely to be able to quit. Nicotine has beneficial effects on attention, concentration and mood. These smokers may be depending on nicotine as a means of self-medication.[20]

Are there important associated adverse health consequences of nicotine intake? Without doubt, nicotine medication is much safer than cigarette smoking, with the latter delivering not only equal or increased levels of nicotine, but also thousands of toxic combustion products to the smoker. However, there are some concerns involving the safety of long-term exposure to nicotine, including cardiovascular disease, cancer and reproductive disorders.[21] Nicotine is a sympathomimetic drug that releases catecholamines, increases heart rate and cardiac contractility, constricts cutaneous and coronary blood vessels and transiently increases blood pressure. Nicotine also reduces sensitivity to insulin and may aggravate or precipitate diabetes, and may also contribute to endothelial dysfunction. These various effects of nicotine on the cardiovascular system could, in theory, promote atherogenesis and precipitate acute ischemic events in people who have coronary artery disease. This has been of particular concern in smokers who use nicotine medication while they are still smoking. However, increased cardiovascular risk due to nicotine medication does not appear to be a problem.[21] Nicotine is not a direct carcinogen, but there are concerns that it may be a tumor promoter. Whether nicotine is a cancer promoter in humans has not been established.[21] Suspected adverse reproductive effects of nicotine include, most prominently, fetal neuroteratogenic effects. In general, it is not desirable to use nicotine during pregnancy, but if the alternative is cigarette smoking, then nicotine medication is undoubtedly less hazardous.[21] Nicotine-replacement therapy used in the long term is well-tolerated without evidence of serious adverse health effects.[22] In conclusion, nicotine per se causes minimal risk when separated from inhaling smoke.

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