“E-Years”: A Proposal for Standardized Quantification of Electronic Cigarette Use

Electronic cigarettes (e-cigarettes) are devices that use a battery to heat a solution (e-liquid), typically with a coil, vaporizing the e-liquid and creating an aerosol (e-aerosol) for inhalation. Since their introduction to the American market in 2007, e-cigarette use has become increasingly popular and has grown into a $3.5 billion market.(1)

Information about the safety and long-term health effects of e-cigarette products is limited and conflicting.

E-cigarettes often are viewed as safer and cheaper alternatives to cigarettes(2) and are popular among individuals who have quit smoking.(3-5) Recent research has demonstrated e-cigarettes to be more efficacious than traditional nicotine replacement therapy when both products were accompanied with behavioral support for individuals interested in quitting smoking.(6) Between 2010 and 2014, there was a statistically significant decrease in smoking rates in the United States, which was associated with a drastic increase in e-cigarette use.(7) In addition, there is a high prevalence of e-cigarette use in adolescents.(8) E-cigarettes are the most commonly used tobacco products for middle- and high school students,(9) and in 2017 it was predicted that 27.7% of eighth-graders had used e-cigarettes.(10) Interestingly, e-cigarette use in adolescents has been associated with increased odds of initiation of smoking tobacco.(11)

Information about the safety and long-term health effects of e-cigarette products is limited and conflicting due to their recent emergence on the market.(12) However, evidence indicates that e-cigarette use is harmful to multiple organ systems(13) and that it is connected to health risks.(14) E-cigarettes, like cigarettes, typically contain nicotine, an addictive alkaloid that can negatively affect the cardiovascular, respiratory, renal, and reproductive systems.(15) Whereas one traditional cigarette delivers 1 to 2 mg of nicotine,(16) e-liquids contain from 0 to 42 mg/mL of nicotine,(17) making it difficult to delineate nicotine exposure and nicotine-related health effects from e-cigarette use. Moreover, there is tremendous variation in e-liquid composition, further complicating the understanding of exposure from e-cigarette use and its potential health effects.

It is important to recognize the similarities between the current state of e-cigarette use and the history of traditional cigarette use in the United States. Before the health risks of cigarette use were identified, cigarette use was ubiquitous and accepted in restaurants, airplanes, and the workplace.(18) However, in 1962, the Advisory Committee to the Surgeon General published Smoking and Health, which included evidence from a plethora of studies linking cigarette smoking to negative health effects. Only then were the negative health impacts of cigarette use widely accepted in the United States.(19) Reaching the conclusion that cigarette smoking was harmful to human health required a comprehensive body of research accumulated over many years, including studies that employed a dose–response relationship by quantifying cigarette use with more sophisticated methods than “smokers” versus “nonsmokers,” such as cigarettes per day, pack-year, or packs per day.(20,21)

Since Smoking and Health was published, continuous efforts have been made to research, document, and screen cigarette use. Moreover, policy has been enacted to limit smoking in work and public places, because there has been increased awareness of the health effects of smoking(19) due to regular screening and documentation by healthcare providers. However, it was not until 2009 that the Food and Drug Administration (FDA) began regulating tobacco products under the Family Smoking Prevention and Tobacco Control Act.(22) The American Recovery and Reinvestment Act, also enacted in 2009, implemented the Health Information Technology for Economic and Clinical Health Act, which outlined clinical quality measures (CQMs) as parameters for Meaningful Use. The 21 CQMs provided incentives for eligible providers and hospitals to meet the outlined requirements through Medicare and Medicaid funding. The most consistently reported CQM has been cigarette screening and documentation in regular history and physicals, with a screening rate of 89.8%.(23) Due to these successful efforts regarding tobacco screening and control, smoking in America has been cut by over half since 1964. As of 2016, however, 38 million Americans still smoked cigarettes.(24) Nicotine, the addictive ingredient in cigarettes, still has a large presence in the United States, as seen by the popularity of e-cigarettes. Moreover, despite the success of tobacco control, the shift toward e-cigarette use has created a new problem that deserves adequate attention and resources.(19) To address these cultural and behavioral changes, in 2016 the FDA released a new rule that states all tobacco products, including e-cigarettes, are under the regulation of the Center for Tobacco Products, which indicates significant progress in surveillance of e-cigarette use and implies that there are negative health risks to this new form of nicotine consumption.(24)

The history of cigarettes should serve as a cautionary tale when considering e-cigarette use in modern society. In the same way cigarettes were used prior to known adverse outcomes, e-cigarettes currently are widely used without public knowledge of long-term health effects. To research the health impacts and epidemiology of e-cigarette use, as well as screen and document e-cigarette use, a standard method of quantification needs to be developed. The absence of a standard method of quantification for e-cigarette use limits the ability to accurately study exposure of e-cigarette use and health outcomes. The purpose of this study is to analyze a rapidly growing collection of literature to identify the manner in which e-cigarette use has been quantified and reported in previous studies, evaluate variations in e-cigarette products and use, and research quantification methods used for traditional cigarettes in order to develop a standard method of quantification for e-cigarette use.

Methods

Our question was “How can e-cigarette use be accurately quantified in a patient-friendly manner in order to facilitate clinical integration of e-cigarette use documentation and screening and further research on the health effects and epidemiology of use?” Our search was conducted using electronic databases (PubMed, Medline, PLOS One, Clinical Key, Ovid) and government websites (National Institute on Drug Abuse, FDA, CDC). The initial search was done with the keywords e-cigarette, e-liquid, and vaping, which returned 3579 articles after duplicates were removed. We further excluded articles that did not contain pertinent information by adding additional keywords (use, usage, composition, quantification), along with filtering for English full-text articles. The remaining articles were screened for relevance using titles, then an abstract review, followed by full-text review of 183 articles, which determine the final 41 articles to be included. The search was performed December 1, 2018, through May 22, 2019. The searches were customized to meet the individual database determinants.

Results/Discussion

Previous Quantification of E-Cigarettes

Prior quantification of e-cigarette usage has been inconsistent, although we identified several studies that quantified vaping in human subjects. Many of the studies quantified e-cigarette users as daily or regular users,(25-27) depending on the number of days of usage over a designated time period.(28) Other studies that compared use of traditional cigarettes to e-cigarettes quantified vaping usage based on daily, weekly, or monthly standards.(29) This system offers data for baseline e-cigarette usage, but includes great variability in the amount of product used within each category. More recent studies have attempted to further quantify e-cigarette usage by measuring daily vaping sessions, number of puffs per session, and average nicotine content of e-liquid.(30) This approach provides more information on vaping parameters, but still lacks a standardized method of quantification.

In an attempt to develop a standard method of quantification of e-cigarette use, categorizing individuals within the aforementioned parameters is limiting for several reasons. An individual who uses e-cigarettes six days out of the week will be categorized as a weekly user, as will other individuals who use e-cigarettes one day out of the week. This variability within categories is problematic because it lacks the ability to accurately measure e-cigarette usage. Future research attempting to predict health outcomes of e-cigarettes will require a more standardized approach of quantification to be able to make accurate correlations.

Current quantification parameters require a large amount of information from individuals, such as daily vaping sessions and number of puffs per session. It is unlikely that an individual is monitoring these specific guidelines and can relay accurate data. Furthermore, this system is difficult to implement in the clinical setting and does not provide a simple method for documentation within medical charts.

Variations in E-Cigarette Products

One of the biggest barriers to developing a standard method of quantification for e-cigarette use is the tremendous variation and dynamic nature of e-cigarette products. It has been estimated that between 2013 and 2014, 10.5 new brands of e-cigarette products and 242 new flavors were produced each month, totaling 466 brands and 7746 flavors of e-liquid by 2014, numbers that had not significantly changed by 2017.(31,32) Three primary types of e-cigarettes are available: 1) disposable e-cigarettes, which are shaped like traditional cigarettes and are prefilled with e-liquid; 2) pen-style e-cigarettes; and 3) tank style e-cigarettes, which are rechargeable, refillable, and may include the ability to adjust the heating temperature and flow rate of the device to alter the content and volume of the e-aerosol.(32,33)

The composition of e-liquids, which are either prefilled in disposable e-cigarettes or sold separately in varying volumes based on milliliters of e-liquid, also varies considerably between products. E-liquids most commonly contain propylene glycol, glycerol, ethylene glycol, aldehydes, polyethylene glycol, and flavoring, with or without nicotine.(34) E-liquids contain from 0 to 42 mg/mL of nicotine. However, there is evidence to suggest that the marketed nicotine levels in e-cigarettes do not match the measured levels. The nicotine content in aerosols depends on its level in the e-liquid and number of puffs, and ranges between –2.94% and 25.2% of the manufacturer’s marketed value.(17) Additionally, some e-cigarettes marketed as containing zero nicotine actually have significant amounts, ranging from 0.01 mg/mL to 23.9 mg/mL across different manufacturers.(35)

E-Years: A Proposed Standard Method of Quantification

The most appropriate quantification method for e-cigarette use should be based on a variable that is constant across the dynamic and rapidly changing e-cigarette market and will remain constant over time as e-cigarette products continue to develop. Despite variations in brands, products, and e-liquid composition, we believe a simple volume-based method of e-cigarette quantification is most appropriate, as measurements by milliliters of e-liquid are constant across products. Disposable e-cigarettes state the mL amount of e-liquid they contain, and refillable e-cigarettes, although their tanks may vary in volume, are filled based on mL amounts. Furthermore, e-liquids are sold based on mL amounts, and it is reasonable to expect individuals to accurately report how much product they purchase.

In formulating a proposed standard, with pack-years as the reference standard, we matched reported customer habits, packaged vaping liquid quantities, and research quantifications to formulate e-years based on milliliters of vaping liquid per day multiplied by years. Instituting e-years, modeled after pack-years, as the standardized method of quantification of e-cigarette use is both accurate and patient friendly; this calculation requires basic data every e-cigarette user can supply, regardless of the type of product used, and is simple enough to allow implementation in every clinic setting.

We propose a standardized method of quantification of e-cigarette use in e-years, defined as the milliliters of e-liquid used per day multiplied by number of years an individual has been using e-cigarette products. This method should include all e-cigarette users regardless of the product used. Additionally, this standard method is similar to traditional cigarette quantification via pack-years (number of packs smoked per day multiplied by number of years an individual has smoked). The pack-year system is widely accepted despite the inherent variability of cigarette composition, nicotine concentration, and differences in puff volumes and filter design.(36)

Reporting of an individual’s e-years will prove to be increasingly valuable as the health effects of vaping continue to be investigated and will provide a basis for more meaningful discussions and clinical interventions. Moreover, the e-years model can be easily integrated into electronic medical records and applied toward longitudinal studies on both the behavior surrounding vaping and its long-term health effects.

Limitations and Future Directions

Standardizing the quantification of patient e-cigarette usage has several different limitations. Although the metric of e-years could be an effective method of quantifying use, the primary limitation to e-cigarette research is the lack of consistency in documentation of patient e-cigarette use by clinicians.(37) We believe that the use of the term “e-years” will facilitate widespread documentation of e-cigarette use in electronic health records and encourage clinicians to ask patients about use.

Additionally, it is difficult to draw a direct comparison with traditional cigarette use, quantified through pack-years. During the course of this review we attempted to compare e-cigarettes with traditional cigarettes using nicotine content, a common ingredient and basis for habit formation in both products. The use of nicotine as a comparison proved difficult for many reasons. First, pack-years do not take into consideration the nicotine content for calculation. The amount of nicotine absorption varies between different traditional cigarettes based on the filter ventilation,(38) as well as the circumference of the cigarette.(39) This variability in nicotine content also is present in e-liquids, as mentioned earlier. Second, cigarette nicotine content is based on the growth of the tobacco plant used, which can be genetically modified to produce different levels of nicotine content,(40) whereas nicotine in e-liquid can be produced synthetically without the use of a tobacco plant.(41) Finally, although the FDA has implemented effective standards and regulations for controlling cigarette nicotine content, similar effective regulations are lacking for e-liquid contents. Furthermore, research has shown differences in e-cigarette use behaviors. Experienced smokers alter their e-cigarette habits in response to decreasing nicotine content in the e-liquid, leading to near constant levels of cotinine (a major nicotine metabolite) in the saliva across different nicotine concentrations.(42)

The use of an average nicotine content is one method by which these limitations may be overcome, and in combination with increasing FDA oversight(24) it may be possible in the future to use an average nicotine value in e-liquid to create a direct, mathematical comparison between e-years and pack-years. Alternatively, longitudinal studies using e-years as a quantification method may show correlations between e-year history and adverse health effects, thus allowing for a comparison to be made between e-years and pack-years based on adverse health effects.

A final concern is how to address additional compounds found in e-liquid. Tobacco-specific nitrosamines, tobacco alkaloids, hydrocarbons, metals, and volatile organic compounds also have been found to be variable in e-liquids,(43) and active pharmaceutical agents can be added to e-liquid.(34) Furthermore, research also has shown the size of inhaled particles may impact distribution and deposition in the respiratory system.(44) More research is needed to determine the health effects of these additional compounds, along with the impact particle size, distribution, and deposition has on multiple organ systems.

Future research should be directed toward the health effects of e-cigarette use, where a standardized method of reporting is imperative. We also anticipate studies on negative health effects as they relate to amount and frequency of e-cigarette use, nicotine concentration, and other potentially toxic chemicals in e-cigarettes or e-liquids. Using e-years as a standard method of quantification will help healthcare professionals document patient e-cigarette use in their medical records, which will facilitate investigation into the negative health effects. We believe implementing e-years as a standardized quantification system in the clinical setting will facilitate patient–physician conversation about e-cigarette use, thereby increasing awareness as well as data available for research on the health effects of e-cigarette use.

Conclusion

A comprehensive literature review documented a lack of standardized reporting of e-cigarette use. In order to identify important health outcomes, health care officials must have a standard way to quantify and report e-cigarette usage. We propose a patient-friendly documentation strategy that meets the needs of patients, researchers, clinicians, and reimbursement providers alike, via usage of e-years, defined as the volume of e-liquid in mL consumed per day multiplied by the number of years an individual has used e-cigarette products.

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