Tox and Hound – Up in Smoke

by Trevonne Thompson

The Outbreak of Electronic Cigarette Use and Pulmonary Injury

There is currently an outbreak of pulmonary injury associated with electronic cigarette use. As of October 8, 2019, the Centers for Disease Control and Prevention (CDC) reports 1,299 cases of lung injury associated with electronic cigarette use from 49 states and 1 U.S. territory. Twenty-six deaths have been confirmed in 21 states. The majority of cases involve young (<35 y) males using THC products. All patients reported using electronic cigarettes. Most report using the electronic cigarette device with THC products. Approximately 70% of patients are male. Eighty percent of the patients are under 35 years old, and 15% are under 18 years old. Many are calling this an outbreak of vaping-associated pulmonary injury (VAPI).

A Brief History of Tobacco Products and Delivery Systems

The tobacco industry has a long-standing history of modifying their products, primarily to increase the customer base or to create long-term users. Some early modifications include making cigarettes more palatable, increasing the nicotine content, and marketing products as “safe.”^​1​ Examples include adding flavoring to cigarettes, developing smokeless products (e.g., chewing tobacco, dissolvable tobacco, etc), and marketing products as “light” (which referred to the tar, not the nicotine content of the cigarette).

The use of electronic cigarettes has been largely targeted to young adults and teenagers. The use of flavoring chemicals in the e-liquid is of particular concern in attracting young users. In one study of 12-17 year olds who use electronic cigarettes, the subjects said they do so “because they come in flavors I like.”^​2​ There are approximately 8,000 flavors available commercially. This is in addition to custom flavors that are made by local shops and the users themselves. The youth predominance of electronic cigarette use plays a large part demographics of those affected by the recent lung injury outbreak.

There have been many innovative attempts at modifying tobacco products and delivery systems. Relevant to this discussion, the first known reference to an electric, not electronic, cigarette was Dr. Scott’s Electric Cigarettes, advertised in Harper’s Weekly in the 1880s.^​1​ Dr. Scott developed a range of “electric” products that would today be defined as quackery. For example, he marketed a line of “electric hair brushes” that contained “curative powers” because of the magnetized iron rods in the handles. In the case of the Electric Cigarette (Figure 1), the gimmick was that the cigarette could be lit directly by striking the cigarette on the cigarette box, obviating the need for matches.

In more modern times, a patent application was placed in the U.S. Patent Office in 1963 for a “smokeless non-tobacco cigarette” that didn’t seem to make it to market. In 2003 a Chinese company developed the first modern electronic cigarettes. By 2007, electronic cigarettes were a part of the U.S. market. Their sales and use have since proliferated.

What is an electronic cigarette?

An electronic cigarette is a device composed of a battery, a reservoir for holding the solution to be inhaled, a heating element or atomizer, and a mouthpiece for the user to inhale. The liquid used in the devices typically contain nicotine, a solvent such as propylene glycol or glycerine, and flavoring chemicals (Figure 2). This liquid has many colloquial names—e-liquid, e-juice, and vape juice being common ones. The electronic cigarettes themselves have many names—e-cigarettes, e-cigs, cigalikes, e-hookas, mods, vapes, vape pens, and tank systems. The electronic cigarette heats the liquid solution, and the user inhales the aerosol. The devices come in many shapes and sizes, often in a pen-like shape with a mouthpiece (Figure 3). Some of the more recent devices, however, look nothing like pens or inhalers. Instead they look like USB memory devices and other less-than-obvious shapes (Figure 4). These devices are designed to deliver nicotine; however, they can be modified (hence the nickname mods) by local retailers or the end users themselves to allow for the use of other substances, such as THC products.

These devices are often called vape pens. Using the devices is often called vaping. The current outbreak is called by some vaping-associated pulmonary injury (VAPI). However, no vapors are actually involved in this process. A vapor is the gas phase of a substance. An aerosol is a suspension of particles of a liquid, a solid, or both within a gas. Electronic cigarette use involves inhaling an aerosol. While “aerosoling with an aerosol pen” doesn’t have the same flair as “vaping with a vape pen,” in scientific discourse this distinction is noteworthy. Heating and subsequently aerosolizing e-liquid creates new substances, such as volatile organic compounds, not present in the original e-liquid.^​3​ Materials from the heating element of the electronic cigarettes may leach into the e-liquid and also become aerosolized.^​3​ Significantly, the toxicity profile of e-cigarette aerosol is known to be different, when studied in vitro, compared to the combustion products of tobacco smoke.^​4​ While the pathophysiology of the current outbreak of pulmonary injury associated with electronic cigarette use is not yet known, I suggest the possibility that aerosolization, and not vaporization, will play a key role.

Electronic Cigarettes and Lung Injury

The lung injury associated with electronic cigarettes is concerning. Many in the medical toxicology field expressed concern with the proliferation of e-cigarettes because of the many unknown potential risks of the practice. While the health effects of nicotine are well known, the effects of inhaling the aerosol flavoring chemicals, solvents, and other products is largely unknown. While it does seem clear that inhaling the aerosolized e-liquid exposes the user to fewer toxic chemicals than smoking, that doesn’t mean that using electronic cigarettes is safe. Indeed, a case report in 2012 describes lung injury similar to the current outbreak in a woman who had recently started using electronic cigarettes.^​5​ There are about a dozen other case reports in recent years that likewise describe a pulmonary illness associated with electronic cigarette use, primarily in young adults.

This past summer, there was a recognition of cases centered in Northern Illinois and Wisconsin.^​6​ This outbreak has since expanded to nearly all of the United States. Patients generally present with a cough, dyspnea, and chest pain. Nausea, abdominal pain, and diarrhea have also been commonly reported. Patients tend to have constitutional symptoms such as fever, chills weight loss, and fatigue. Chest radiography may show diffuse infiltrates similar to atypical pneumonia. Computed tomography of the chest shows bilateral ground glass appearance. Testing for infectious causes and rheumatologic causes is normal. Many patients have required ICU admission and ventilator support. A number of patients have developed acute respiratory distress syndrome (ARDS). Some patients have even required extracorporeal membrane oxygenation (ECMO). See Table 1 for the CDC case definition of the vaping-associated pulmonary injury.

The Challenges

The cause of lung injury associated with electronic cigarette use is not known. No single product or substance has been linked to all cases. There is not enough information known yet to determine if a single product, substance, method of use, or brand is responsible for the outbreak. About 76% of affected patients report using THC-containing products. Since e-cigarettes are not specifically designed for THC products, there is concern that this outbreak is related to custom or homemade products and e-cigarette device modifications. To highlight some of the complications in determining a source, the CDC reports significant crossover in e-cigarette product use. In addition to the 76% of patients who report using THC-containing products, 58% report using nicotine-containing products, 32% report the exclusive use of THC-containing products, and 13% report the exclusive use of nicotine-containing products. Further, the investigation involves many states, over a thousand known patients, and hundreds of electronic cigarette devices and products. This is all in addition to the underground electronic cigarette market as demonstrated by a recent investigation in Milwaukee, WI, where two brothers and their mother were arrested for running an underground electronic cigarette operation – 31,000 e-liquid cartridges containing THC oil were confiscated.

What Next?

The CDC is actively investigating this outbreak in conjunction with the FDA, local and regional health departments, and other investigators. The CDC is now calling this an outbreak of e-cigarette, or vaping, product use associated lung injury—or EVALI. The CDC recommendations for the public are in Table 2. The latest CDC guidance and recommendations for clinicians can be found here.

While the investigation is continuing and recommendations evolving, there are a few important concepts to keep in mind. Be vigilant when taking a history on a patient with respiratory complaints, especially as the influenza season approaches. Report suspected cases to your local health department. Engage with your local health departments and government officials to guide the public health and policy responses to the outbreak.

Summary

An outbreak of pulmonary injury associated with electronic cigarette use, largely in young adults, is ongoing. The etiology has not yet been determined, but there is a high association with the use of THC products in the electronic cigarettes. This suggests that customization of the e-liquid or modifications to the electronic cigarette devices may be related to the cause of the disease. Emergency physicians, medical toxicologists, and other physicians and health care providers should remain vigilant in recognizing the disease and identifying those at risk.