Lung Disease and E-Cigarettes

Widespread electronic-cigarette (EC) use has led to increased interest in its correlated adverse health effects. United States Surgeon General Jerome M. Adams, MD, MPH, labeled the rising use of EC among youth as an epidemic.¹ He advised the need for immediate action to protect young people from avoidable health risks associated with nicotine addiction, including risks to respiratory health and brain development.¹ The purpose of this article is to review current knowledge about adverse health effects caused by vaping EC and the role of oral health professionals in assessment and patient education to reduce associated harms.   

As of February 18, 2020, a total of 2,807 hospitalized e-cigarette, or vaping, product use-associated lung injury (EVALI) cases had been reported to the US Centers for Disease Control and Prevention (CDC) from all 50 states, the District of Columbia, Puerto Rico, and US Virgin Islands. The outbreak in EVALI cases began in June 2019 and peaked in September. Although the number of new hospitalized cases and possible cases presenting to the emergency department have been declining since September 2019, EVALI is still a major public health concern.²

New information is emerging about how EC use contributes to lung disease. Bronchoscopy data taken from healthy never-smokers who volunteered to vape an EC containing 50% each of the solvents propylene glycol (PG) and vegetable glycerin (no nicotine) for 4 weeks revealed minimal but measurable signs of inflammation in both their lung tissue and lung fluid. The level of PG found in their urine significantly correlated with elevation in macro­phages and several pro-inflammatory cytokines (IL-8, IL-13, and TNF-ɑ). These pilot data are among the first to demonstrate the development of inflammation caused by EC use among never-smokers.³

A research group at the Center for the Study of Tobacco Products at Virginia Commonwealth University suggests that PG and vegetable glycerin dry up tissues and that they are being inhaled across membranes in the throat and upper airways that need to remain moist.⁴ Further, because both PG and vegetable glycerin act as solvents, they may dissolve lung surfactant that keeps the alveoli from collapsing for proper gas exchange.

Macrophages not only protect against infection, but they help to recycle surfactant.⁵ Findings in mice support that chronic exposure to EC vapor compromises macrophage immune function and alters the homeostasis of surfactant independently from nicotine.⁵ Biopsy data taken from eight men with vaping-associated pulmonary illness revealed acute lung injury and diffuse alveolar damage, with macrophages found in the airspaces in all cases.⁶ Among these eight cases, all reported vaping tetrahydrocannabinol (THC)-containing products, implicating that either the THC itself or a toxic component within the THC-containing vape fluid produced tissue injury.⁶

TOXINS IN E-CIGARETTES AND ASSOCIATED PRODUCTS

The most recent human study examined toxicants found in the fluid obtained following a bronchoalveolar lavage (BAL) in 51 hospitalized patients with EVALI.⁷ Investigators reported that 48 of the 51 EVALI patients (94%) had vitamin E acetate present in the fluid. Most (94%) had detectable THC or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 out of 47 case patients (64%), confirming dual vaping of nicotine and THC. The CDC reported that 152 different THC-containing product brands were reported by patients with EVALI.²

Vitamin E acetate is a cutting agent often used in illicit THC-containing products as a thickener to lower product cost.^8,9 While vitamin E acetate is generally recognized as safe for ingestion and topically in dermatologic products, it is not safe for inhalation. Once in the lungs, its biotransformation allows vitamin E to penetrate the surfactant layer, reducing the surface tension needed to keep alveolar sacs open and functional during respiration.^10,11 Also, the byproduct of heating vitamin E acetate is ketene, a reactive compound that acts as a lung irritant.¹²

While vitamin E acetate remains a chemical of concern, the US Food and Drug Administration (FDA) is currently testing more than 1,300 samples from across the country to look for additional compounds with implications in EVALI. Approximately 1,060 of these samples are linked to patient cases being tracked by the CDC; others come from vaping devices and associated products. As of January 15, 2020, approximately 810 samples had undergone testing, and, of these, two-thirds were found to contain THC, and half of those contained vitamin E as a diluent. Among 79 CDC case patients, 76% had samples containing THC. Of those, identified diluents in their samples included vitamin E acetate (77%), aliphatic esters (33%), and PG (8%).¹³ The concentrations, source, and pattern of use/exposure of these and other substances are all critical variables in the development of respiratory disease and require ongoing study. It is likely that there is more than one cause for EVALI.¹³

EC aerosols also contain toxic agents, including heavy metals, nitrosamines, diethylene glycol and carbonyls (formaldehyde, acetaldehyde, acrolein), and reactive oxygen species (ROS) that are directly inhaled by the user. Carbonyls and ROS are formed when the cartridge liquid contacts the heating element.¹⁴ ROS and other free radicals induce oxidative stress, which damages cell proliferation and survival. Most tobacco-related diseases, including cancer, are associated with oxidative stress.¹⁵ Bitzer et al¹⁶ found that generation of free radicals was highly dependent on the PG content of the EC liquid. They have recently reported that after testing 49 commercially available e-liquid flavors, 43% resulted in significant increases in free radical production as compared to the base liquid containing PG and glycerin.¹⁵ Additional research is needed to understand how different flavoring agents contribute to potential harm, given that flavor is appealing to youth and young adults.¹⁷

Some believe EC use is safer than conventional cigarettes. Levels of known carcinogens in EC liquids and aerosols are lower than levels found in tobacco and tobacco smoke, with the exception of formaldehyde and other small aldehydes.¹⁸ However, many EC users are also concurrent tobacco users, placing them at risk for increased exposure to carcinogens. It is likely that these dual users have precancerous cells in their oral cavity.¹⁹ New research found that a condensate of EC aerosol enhances the metabolism of a known tobacco carcinogen, benzo(a)pyrene in human oral keratinocytes.¹⁹ This is the first study to show that EC use may enhance carcinogenic risk in current smokers, but also may predispose EC users who are currently never-smokers to developing oral cancer upon initiation of conventional tobacco use. EC vapor, with and without nicotine, causes DNA strand breaks, another potential mechanism for promoting oral cancer.²⁰

ADDICTION

A recent study in mice found that daily exposure to nicotine vapor for 6 months activates nicotine dependence pathways.²¹ Notably, the study found decreased concentrations of the inhibitory neurotransmitter GABA and excitatory stimulation in central reward areas of the brain. This stimulation may facilitate nicotine-seeking behavior.²¹ GABA inhibits the release of dopamine, which normally surges after exposure to nicotine and other drugs, suggesting that GABA has a role in dampening nicotine cravings and smoking behavior.²² But, if chronic exposure to EC vapor decreases the concentration of available GABA, dopamine increases following exposure to nicotine in the aerosol could go unchecked, promoting dependency.²¹

Study findings underscore ongoing concerns that younger EC users who report the highest rates of vaping may become addicted to nicotine.²³ Concerns are magnified given that young EC users are also more likely to start smoking traditional cigarettes.²⁴ Several studies support that EC use is a gateway to conventional cigarette use, with results from a recent meta-analysis reporting that EC use was associated with a three-fold higher risk of subsequent conventional cigarette initiation among ever (vs never) EC users and four-fold higher likelihood for initiating conventional cigarette use within the past month among past 30-day EC users.^25,26

However, experimentation among adolescent never-smokers and transitioning to use is bidirectional. While EC experimentation has been positively associated with progression to conventional cigarette use,²⁷ ever using a combustible tobacco product has also been associated with initiating EC use.^28,29 Impulsiveness and risk-taking behaviors may predispose young people to experimenting with either of these products.²⁹

There is good news. A recent meta-analysis found that among adolescents in the United Kingdom, most EC experimentation does not turn into regular use, and regular EC use among those who have never smoked traditional cigarettes remains low.³⁰ Similar findings have been found in the US.³¹ And traditional smoking has consistently declined over the past decade among adolescents despite the rise in experimenting with EC. The bad news is that the number of individuals who vape nicotine and marijuana daily continues to rise. Adolescents reported their reasons for vaping included: for experimentation, flavor, social reasons, and to feel good.³²

Given comparable THC levels, vaping marijuana produces greater adverse physiological and psychological effects, such as lung disease, compared with smoking marijuana.³³ In October 2019, the FDA issued a warning to consumers to stop using THC-containing vaping products and any vaping products obtained off the street.³⁴ Not all teens know what is in the products they are vaping.³²

In adult smokers, the evidence strongly supports that vaping nicotine is safer than smoking conventional cigarettes.³⁵ Randomized clinical trials support that vaping nicotine is more appealing and effective than using FDA-approved nicotine replacement therapies for smoking cessation.^36,37 Completely substituting vaping nicotine for smoking traditional cigarettes reduces exposure to toxins and carcinogens.³⁸ Like young users, adults also prefer flavored EC, which may help them transition away from cigarette smoking. Evidence shows that most adults who completely switch to vaping only do so only after a period of dual use.³⁷ There is an increasing number of EC users who are former smokers, thus supporting the argument in favor of EC use for smoking cessation.²⁵

IMPLICATIONS FOR DENTAL PROFESSIONALS

On December 16, 2019, the American Dental Association announced its new interim policy on vaping, calling for “a total ban on vaping products that aren’t approved by the [FDA] for tobacco cessation purposes.” The policy stresses advocacy for banning the sale and distribution of all EC and vaping products, except for those approved by the FDA for tobacco cessation (and made available by prescription only), and advocacy for research to further study the safety and efficacy of EC and vaping products for tobacco cessation purposes and their effects on the oral cavity.³⁹

Dental professionals play an important role in assessing patients for EC use and for educating users about associated harms. For those who are using EC to quit smoking, patients should be instructed to avoid conventional cigarettes and encouraged to use FDA-approved smoking cessation therapies.² Patients should be counseled to avoid the use of THC-containing EC or other vaping products, particularly those obtained illegally, and to never add anything to EC or other vaping products.² Patients who demonstrate signs of and/or who report symptoms of respiratory disease should be referred for immediate medical evaluation. Additionally, patients dependent on cannabis should be referred to an appropriate healthcare professional and/or substance abuse program for recovery.² Clinicians are urged to remain current with new knowledge about adverse health effects of EC so they can effectively advise their patients.

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From Dimensions of Dental Hygiene. May 2020;28(5):28-31.