Effects of electronic cigarette aerosol exposure on oral and systemic health

Abstract

Conventional cigarette smoke harms nearly every organ of the body and is the leading cause of death in the United States and in the world. Decades of research have associated conventional cigarette smoke with several diseases and death. Heavily marketed, electronic nicotine delivery systems such as electronic cigarettes (e-cigarettes) are available in a variety of flavors and high nicotine concentrations. In 2019, a severe lung disease outbreak linked to e-cigarette use led to several deaths, which was called electronic-cigarette or vaping product use-associated lung injury (EVALI). Even though the trend of e-cigarette use among teens continues to increase, information on the effects of e-cigarette smoke on oral and overall health are still scarce. This review discusses the possible health effects due to unregulated e-cigarette use, as well as the health effects of second-hand smoke and third-hand smoke on non-smokers.

Tobacco leaves are the major materials used to make cigarettes, cigars, and pipe tobacco. Cigarette consumption and exposure is a worldwide issue that has devastating health, social, economic, and environmental consequences. Despite years of efforts to reduce tobacco consumption, the World Health Organization has estimated that tobacco use and exposure is currently responsible for the death of about six million people across the world each year [1]. According to information from the U.S. Department of Health and Human Service, the total economic cost of smoking is over $300 billion a year, which includes the direct cost of medical care and indirect cost of lost productivity [2].

Cigarette smoke contains a deadly mix of more than 7000 chemicals, including hundreds that are toxic and approximately 70 that are known cancer-causing substances [3]. Decades of studies have associated chemicals in tobacco smoke with higher risks of cardiovascular disease, cancer, pneumonia, diabetes mellitus, rheumatoid arthritis, impaired immune functioning, and genetic diseases of the fetus [2,3]. Cigarette smoking also increases the risk of developing orofacial clefts in infants, and alveolar bone loss, periodontal disease, and oral mucosa cancer in adults [3]. In addition, there is increasing evidence showing that smoking increases dental caries in permanent teeth and is a risk factor for dental implant failure [4,5].

Although electronic cigarettes (e-cigarettes) have been described as a healthier substitute to tobacco smoking, the aerosol of e-cigarettes still contains a wide range of deleterious products [6]. Chronic exposure to these substances at a much higher level than in the air remains a great health risk for smokers and people passively exposed to the e-cigarette vapor [7].

Electronic cigarettes and their impact on smokers' health

E-cigarettes are classified as electronic nicotine delivery system (ENDS) by the U.S. Food and Drug Administration. They are battery-operated devices that were primarily designed to heat nicotine and flavoring containing chemical substances to produce a smokeless vapor called aerosol, which is inhaled by the user [8,9]. The e-cigarette solution in the cartridge is referred to as e-liquid or e-juice and is generally comprised of nicotine, flavor ingredients in propylene glycol, and vegetable glycine. In addition, some vaping devices contain cannabis, which further broadens the composition and appeal of aerosols [10]. The cartridge may also contain heavy metals such as nickel, tin, lead or chrome [11,12]. Even though there are fewer components in e-cigarettes compared to conventional cigarettes, e-cigarettes still contain toxic and cancer-causing residues, such as formaldehyde, acetaldehyde, and acrolein [6].

E-cigarettes are operated by a battery that generates an electrical current that ignites a filament located on an atomizer. The ignited filament evaporates the e-liquid in the cartridge to produce an aerosol. However, ignition of the filament also causes transfer of heavy metals and nanoparticles to the aerosol that can infiltrate the lungs and damage health [11]. Some brands of e-cigarettes contain a sensor that detects the drag and initiates a cascade of events to activate the e-cigarette. When a sensor is not built in, a button that closes the system on the battery and generates the electrical current to power the filament is usually supplied. Depending on the brand, some devices have a LED light that shows when the device is activated or needs to be recharged [9,13]. Some examples of ENDS devices are shown in Fig. 1.

Fig. 1.

Examples of different electronic nicotine delivery system (ENDS) commercially available.

The design of e-cigarettes rapidly evolved since they were originally manufactured in China in 2003 by the pharmacist Hon Lik. There are four generations of e-cigarettes so far with differences including shape, size and prices [14]. The first generation of e-cigarettes resembled closely conventional cigarette and were made of three components: the battery, and the atomizer which was either combined with or separated of the cartridge. The second generation, called cleoatomizers, operated via a multi-voltage battery, a removable filament and had a larger tank capacity that could be removed to refill with e-liquid [15]. The third-generation devices, called “mods”, are characterized by a modified battery with varying voltages, wattage, and power capacity. The fourth generation devices operate with a fixed voltage battery and can have different battery styles and shapes, such as a USB flash drive [13].

E-cigarettes are considered to be safer and healthier compared to conventional cigarettes [16]. Consequently, ENDS use has drastically increased among smokers, including among U.S. youth. Among middle school and high school students, the use of e-cigarettes has continued to increase from 48% to 78% (from 2017 to 2018) [17]. According to a survey with 45,971 U.S. adults and youth, 81% of youth who smoked tobacco products (aged 12–17 years old) reported that their first e-cigarette was flavored [18]. Another study with 150,000 participants showed that 27% of individuals who have ever tried e-cigarettes continued to smoke at least once every 30 days [19]. Regular e-cigarette use was higher in U.S. states with lower cigarette taxes compared with states that have higher cigarette taxes [19].

Nicotine and its effects on smokers

Nicotine is found in conventional cigarettes and e-cigarettes and is the major chemical component responsible for addiction in tobacco products [3]. According to e-cigarette manufacturers, a single e-cigarette device may contain as much nicotine as a pack of 20 conventional cigarettes [20]. A recent CDC study demonstrated that 99% of the e-cigarettes sold in the U.S. contain nicotine, some labels do not disclose whether they contain nicotine, and some of them contain nicotine even though they are marketed as 0% nicotine [21]. Using devices that contain nicotine during adolescence can impair parts of the brain responsible for attention, learning, mood, and impulse control. The brain continues to develop until approximately age 25 and every time a new memory is created, or a new skill is learned, stronger synapses are built between neurons. Nicotine can affect the way in which these synapses are formed. Using nicotine during adolescence may also increase the risk for future addiction to other drugs [22]. In fact, a study with 1,312 teenagers in Southern California showed that e-cigarette users were more likely to smoke conventional cigarettes after a one-year follow-up. Additionally, participants who used mods smoked >6 times as many cigarettes at follow-up compared with vape pen smokers [23].

Effects of e-cigarettes on oral health and the oral microbiome

The oral microbiome is the second most abundant and one of the most diverse microbiomes in the body, comprising over 600 species, with distinct subsets predominating at different microenvironments [24]. Under normal and healthy conditions, the oral microbiota is considered as a commensal because it exists in harmony with the individual host [25]. However, under dysbiotic conditions, some bacterial species such as Porphyromonas gingivalis can lead to periodontal disease and others, such as Streptococcus mutans, can promote dental caries [25]. There is a large body of evidence showing that conventional cigarette smoking is a risk factor for periodontal disease and dental caries [[26], [27], [28], [29]]. However, studies on whether e-cigarettes are risk factors for dental caries and periodontal diseases are still scarce.

The salivary microbiome analysis from 119 participants showed that the abundance of the Gram-negative bacteria Porphyromonas and Veillonella was higher among e-cigarette users compared with conventional cigarette smokers or never smokers [30]. A pilot study with 20 recruited participants showed statistically significant increase in gingival inflammation when participants switched from smoking conventional cigarettes to e-cigarettes [31]. However, the same study showed that high levels of variation in the levels of the pro-inflammatory cytokines IL-8 and IL-1β made these measurements not conclusive. A more controlled study involving 135 participants evaluated pro-inflammatory markers (IL-1β, IL-6, IFN-γ, TNF-α and MMP-8) in the oral cavity and showed increased levels of these markers in conventional cigarette-smokers compared with never-smokers; however, there were no differences between e-cigarette users and never-smokers [32]. Regarding dental caries, an in vitro study shows that the combination of the viscosity of e-liquids and some classes of chemicals in sweet flavors may increase the risk of cariogenic potential. The data available so far must be interpreted with extreme caution, especially because different studies use different brands of e-cigarettes that may have large differences in composition.

Electronic-cigarette or vaping product use-associated lung injury (EVALI)

It is likely that e-cigarette users can also experience systemic effects due to e-cigarette aerosol components. In recent investigations, the U.S. CDC, U.S FDA and U.S. state health authorities have linked hospitalizations to the use of vaping products [[33], [34], [35]]. An outbreak with many patients showing acute and severe respiratory symptoms has compelled health agencies to conduct studies on e-cigarette or vaping product use-associated lung injury (EVALI).

Symptoms associated with EVALI include chest pain, shortness of breath, fever, nausea, and vomiting. According to the CDC, as of February 18, 2020, a total of 2,807 hospitalized cases or deaths were reported from all 50 states, the District of Columbia, Puerto Rico and U.S. Virgin Islands [[33], [34], [35]]. Prevalence among cases of EVALI patients were: 15% were under 18 years of age, 78% (the majority) were between the age of 18 and 34, and 23% were over 34 years old. Hospitalized patients reported using vaping products that contained either nicotine or THC that they obtained from an informal source, shop or a dispensary [[33], [34], [35]]. Screening bronchioalveolar lavage of EVALI patients have pointed to alpha tocopherol, otherwise known as vitamin E, as the potential cause of the disease due to its detection in 94% of patients with EVALI [36]. Analysis by mass spectrometry of vaping products cartridges and pods received from patients showed that vitamin E was present in 80% of THC cartridges [37,38]. As a supplement or an ointment, vitamin E is usually administered orally or applied on the skin and is harmless. However, when used as a diluent of vaping products, it could have toxic effects in the lungs, such as inducing strong inflammation [38]. Fortunately, hospital admissions for patients with EVALI have significantly decreased since the peak of the outbreak in September 2019. In February 2020, the CDC has low numbers of hospitalizations on their database [[33], [34], [35]].

Second-hand and third-hand smoke and their health impacts in non-smokers

Second-hand smoke is the smoke accidently inhaled by a non-smoker. Smoke and aerosols directly from conventional cigarettes, e-cigarettes, marijuana, hookahs, and the smoke exhaled by smokers are considered second-hand smoke and aerosols. Second-hand smoke and aerosols from cigarettes, e-cigarettes, marijuana, and hookah are toxic and contains cancer-causing agents. Data from 192 countries worldwide showed that 40% of children, 33% of male non-smokers and 35% of female non-smokers were exposed to second-hand smoke in 2004 [39]. In addition, 603,000 deaths were attributed to second-hand smoke, which corresponded to 1% of worldwide fatalities [39]. According to the California Department of Public Health, over 50% of Californians were still exposed to second-hand tobacco smoke in 2018 [40].

Second-hand smoke is harmful to the overall health and can lead to death by ischemic heart disease, lower respiratory infections, asthma and lung cancer [39]. Chemicals from e-cigarette aerosols, such as nicotine and cancer-causing alkaloids, were found to be transferred from a vape shop to a nearby business in a multiple-tenant retail building [41]. Exposure to second-hand marijuana smoke can lead to accumulation of cannabinoid metabolites in bodily fluids, and people experiencing psychoactive effects after such exposure [42]. Second-hand smoke is also dangerous to the general population but especially children. Some harmful effects to children involve increasing risks of respiratory symptoms, obesity, disorders of the ear, nose, throat and sleep-disorder breathing [43]. Second-hand smoke can infiltrate into other units in a building [3]; therefore it is important to maintain as much smoke-free space as possible. Because second-hand smoke is visible, extensive research has been conducted approaching this issue. However, third-hand smoke is an understudied public health concern and the potential risks to human health are rising.

Third-hand smoke is a relatively new phenomenon that was first described in 2009 [44]. Third-hand smoke is the residue from tobacco smoke gases and particles (from conventional cigarettes, e-cigarettes, and other tobacco products) that cling to nearby surfaces such as clothing, bags, skin, hair and furniture after tobacco product consumption. The residual tobacco smoke pollutants can persist for minutes to months in indoor environments and on surfaces [45]. The exposure to third-hand smoke present in dust, air and surfaces can occur through dust ingestion, dermal absorption and inhalation [45]. Young children are especially vulnerable due to their crawling, hand-to-mouth and exploratory habits. E-cigarettes were shown as a source of third-hand exposure to nicotine that was recovered from windows, walls, floor, wood and metals [46]. Exposure to these residues can cause DNA damage and increase the risk for short-term and long-term health problems, including asthma and cancer [[47], [48], [49]].

Traditional cleaning methods may not be effective in removal of third-hand smoke compounds due to their ability to strongly adhere to surfaces [50]. In fact, it is estimated that vacuuming and wiping strategies may help to release the residual compounds from surfaces to the air as aerosols [50]. To remove these third-hand smoke residues from surfaces, fabrics and other materials, regular cleaning and/or laundry should be performed.

Can e-cigarettes help adults quit smoking?

Outside of the U.S. (particularly in the United Kingdom and other parts of Europe), e-cigarettes are viewed very differently. The National Health Services in the UK have embraced e-cigarettes as a harm-reduction strategy and safer alternative to the thousands of chemicals found in conventional cigarettes [51,52]. The UK places limits on the amount of nicotine allowed in their e-cigarettes (up to 20 mg/mL of nicotine [53], whereas the U.S. has no limit (some brands currently have up to 87 mg/mL [54]). These different approaches to e-cigarettes have resulted in a dramatically different teenage e-cigarette rate in the UK, which is only 2% [55,56] compared to 20% in the US [57]. These differences raise obvious questions for the US: Should nicotine levels in e-cigarettes be regulated? Should e-cigarettes be advocated as a safer alternative to traditional cigarettes?

Several studies and systematic reviews support the view that e-cigarettes may be used as a harm-reduction strategy. Hajek et al. [58] conducted a randomized control trial that showed adults who were given e-cigarettes had double the abstinence rate after 1 year (18.8% compared to 9.9%) [58]. In this study patients were randomly assigned to use e-cigarettes or a traditional nicotine-replacement product of their choice (patch, gum, lozenge, nasal spray, inhalator, mouth spray, mouth strip, and microtabs), and the patients on e-cigarettes had a higher cessation rate, lower levels of nausea, lower levels of phlegm production, but higher throat irritation. Liu et al. [59] conducted a systematic review of 14 different studies and 35,665 participants, finding that the efficacy rate of e-cigarettes ranged from 48.3% to 58.7% for smoking reduction and from 13.2% to 22.9% for smoking cessation [59]. As a cautionary note, Hendlin et al. [60] warned that studies that disclosed financial support from the tobacco industry had higher rates of support for e-cigarettes as a smoking-cessation device (58% compared to 50% [60]). While these results are promising, most of the studies are still limited, and several studies commented that there is a lack of longitudinal data for e-cigarettes due to their short time on the market.

Final considerations

Smoking can harm nearly every organ of the body [3] and is considered the leading cause of death in the U.S. and the world. Several decades of research have demonstrated the harmful effects of conventional cigarettes. Although there have been several recent reports on the damaging health effects related to e-cigarette use, more research in the future will reveal the full extent of harm due to e-cigarette use. The harmful effects of conventional cigarettes and e-cigarettes use are summarized in Table 1, and a summary of the harmful effects of smoking are shown in Fig. 2. There is no safe level of tobacco smoke, and a better understanding of the risks imposed by tobacco smoke can help in prevention of tobacco-related diseases. Furthermore, second-hand and third-hand smoke are public health issues that should be taken into consideration in order to improve the overall health of the general population.

Table 1.

Harmful health effects due to the use of conventional cigarettes and e-cigarettes.

Smoking device	Health effects	References
Conventional cigarette	Oral conditions
	Bad breath, stained teeth and tongue, dulled sense of taste and smell, slow healing after tooth extraction or surgery	[3]
	Dental caries	[61,62]
	Periodontitis	[63,64]
	Cleft lip and palate	[65,66]
	Oral cancer	[67]
	Systemic conditions
	Heart disease and coronary heart disease	[3,[68], [69], [70]]
	Stroke	[71]
	Cancer (breast, colon, head and neck, lung)	[[72], [73], [74], [75], [76], [77]]
	Diabetes	[78]
	Chronic obstructive pulmonary disease	[3,79]
	Inflammation and decreased immune function	[23,[80], [81], [82]]
	Preterm delivery, low birth weight, birth defects, ectopic pregnancy, reduced fertility	[3,83,84]
	Rheumatoid arthritis and lupus erythematosus	[85]
	Second-hand smoke exposure	[39,40,86,87]
	Third-hand smoke exposure	[44,45,88,89]
E-cigarette	Oral conditions
	Dental caries, toothache, periodontal disease	[[90], [91], [92]]
	Oral lacerations, teeth fractures and avulsions due to e-cigarette explosions	[90]
	Systemic conditions
	Reduced control of attention, learning, mood, and impulse	[22]
	EVALI	[[36], [37], [38]]
	Second-hand smoke exposure	[41]
	Third-hand smoke exposure	[46]

Fig. 2.

Scheme illustrating the different ways that smoking or vaping can affect overall health. The figure shows examples of smoking causing harm to oral health and systemic health, as well as second-hand smoke and third-hand smoke being harmful to non-smokers. Smoking is associated with higher risks of developing periodontal disease, caries, and oral cancer. It is also associated with systemic diseases such as respiratory and cardiovascular disease, adverse pregnancy outcomes and cancer. Second-hand smoke can affect non-smokers and may cause asthma and lung cancer. Third-hand smoke (pollutants that cling to furniture and overall surroundings) is dangerous especially to children due to their hand-to-mouth and exploratory habits. This image exemplifies a smoker using a common computer and leaving third-hand smoke to the next user. This image was created in BioRender.com.

Conflict of interest

The authors declare no conflict of interest.