Travis S. Henry
Associate Professor of Clinical Radiology
University of California, San Francisco
Published January 10, 2020
The latter half of 2019 saw the identification of an entirely new respiratory illness and introduction of a new diagnosis— e-cigarette, or vaping, product use associated lung injury (EVALI)—into the medical lexicon. Based on current understanding, EVALI is an acute or subacute respiratory illness that is often severe and in some cases fatal, purported to be a chemical pneumonitis resulting from inhalation of one or more toxic substances. As of November 5, the Centers for Disease Control (CDC) reports 2,051 cases of EVALI in the United States, including every state except Alaska, plus the District of Columbia, with 39 deaths in 24 states. The reported cases have affected patients as young as 13 and as old as 75, with males about twice as common as females. Nearly all of these patients have presented with acute or subacute respiratory symptoms, and not surprisingly, thoracic imaging (chest radiograph and CT) has become central to the diagnosis of these patients. Knowledge about these diseases is changing every day, and it is imperative that diagnostic radiologists have a general understanding of what vaping is, how it looks on imaging, and what we know so far.
What Is an E-cigarette, and What Is Vaping?
An e-cigarette is an electronic device that is designed to simulate traditional smoking. Instead of the combustion of tobacco (or, more recently, marijuana), e-cigarettes heat a substance (usually liquid, oil, or wax) to create a vapor that is inhaled, hence the term “vaping.” E-cigarettes were invented in 2003 and introduced in the U.S. around 2007.
Most devices have three main components: a chamber or cartridge that contains the substance to be heated and vaporized (also referred to as the e-liquid); an atomizer or heating element that vaporizes the substance in the cartridge, so that it can be inhaled; and a battery to power the heating source.
Like any piece of technology, these devices have evolved and are becoming increasingly sophisticated. Early devices tended to mimic tobacco cigarettes in shape, but now admittedly look outdated, compared to the most recent generations of products that are smaller, sleeker, and more easily concealed. Some bear more of a resemblance to USB thumb drives than smoking devices, and a few even have Bluetooth connectivity to track how much one vapes.
What Substances Do People Vape?
The substances that patients vape are almost limitless, and this variability is one of the main reasons it has been so difficult to pinpoint the recent surge of cases on one specific cause. A majority of recent cases have been associated with vaping tetrahydrocannabinol (THC) or other marijuana derivatives, and there is mounting evidence for vitamin E acetate as one of the main culprits. While a majority of patients with EVALI report vaping both THC and nicotine, some patients report vaping exclusively nicotine, so it is possibly not just the vitamin E acetate, a thickening agent in THC-containing vaping products, that is to blame.
At this time, there is little regulation of the vaping industry, although the FDA announced in September that it plans to begin regulating some of the nicotine-based substances, particularly flavored products that are perceived to be more attractive to adolescents and young adults. Some cities, such as San Francisco, have begun instituting bans on sales of e-cigarettes.
Given the lack of regulation, there are many ways that the substances are stored, filled, and refilled, as well as many suppliers from where patients get their vaping substances. Some are refillable cartridges, whereas others are disposable pods; some people create their own “home brews” or buy products off the street that may not be sterile and may be adulterated. It is suspected that some of the aftermarket or “off-the-street” products may be more likely to cause injury, and the CDC advises against their use.
Nicotine is often mixed with flavoring agents or “vape juice,” and there are more than 15,000 different flavors. Adults may prefer more traditional flavors such as tobacco, mint, or menthol that try to mimic the taste of cigarette smoking. But other flavors more unabashedly appeal to teenagers and adolescents—many of whom were never smokers prior to vaping. A study in Pediatrics found that adolescents who vaped these nontraditional flavors (including fruit, candy, sweet or dessert, buttery, or other blends not including traditional flavors) were more likely to continue vaping at six months and take more puffs per occasion. The use of these flavors resulted in greater self-reported addiction and satisfaction in another study of young adults.
Why the Recent Rise in Vaping Cases?
Vaping is becoming more popular, particularly among adolescents and young adults; the variety of substances that can be consumed has expanded; and e-cigarette companies have increased the marketing of their products, just to name a few. But with the constant media coverage, everyone thinks about vaping as a cause of lung injury, and that has led to increased recognition by physicians, including radiologists.
The first case we suspected to be lung disease due to vaping was in 2014 in an adult male patient with ground-glass opacity (GGO) on CT, although this case could never be proven, as there wasn’t even a name for this disease then. The first confirmed case we saw was in 2017 in a female who was vaping THC to help her sleep. Case reports of EVALI date back to 2012, but our original article in AJR, “Imaging Findings of Vaping-Associated Lung Injury,” is the first to review and present all of the different imaging patterns that we have encountered so far. The varied appearances underscore the confusion and difficulty in these cases, arguing in support of a multifactorial cause.
What’s the Bare Minimum Radiologists Should Know About Vaping and EVALI?
At the time of submission of our manuscript to AJR, there was no accepted case definition for what constituted vaping-associated lung injury. However, based in part on the work since published by Leyden et al. in the New England Journal of Medicine on the cases reported to the Illinois and Wisconsin state health departments, the CDC has proposed definitions of confirmed and probable cases. It must be emphasized that EVALI is still a diagnosis of exclusion, as there is no laboratory test to confirm the diagnosis.
A confirmed case of EVALI is defined as:
- using an e-cigarette or dabbing (i.e., heating concentrated cannabis oil or wax and inhaling the vapors) in 90 days prior to symptom onset
- abnormalities on either chest radiograph or CT
- negative infectious workup
- no alternative plausible diagnosis (e.g., cardiac, rheumatalogic, or neoplastic)
A probable case of EVALI is similar—the one distinction that either an infection was detected by culture or polymerase chain reaction but not suspected of being the sole cause of lung injury, or minimum testing to exclude infection was not performed.
Imaging is part of the case definition, and as such, radiologists are critical to the diagnosis. The CDC definition verbatim is “pulmonary infiltrate, such as opacities, on plain film chest radiograph or ground-glass opacities on chest CT,” but to any radiologist, this sounds like a vague and generic explanation. One can review the many different patterns of lung injury in our AJR paper, but the one commonality from the cases we present, our review of the literature, and those cases we’ve encountered since is that these patients almost universally present with bilateral opacities that look like acute lung injury and/or organizing pneumonia. Cases may be diffuse, upper- or lower-lobe predominant.
In the appropriate clinical setting, it is arguable that chest radiograph should be sufficient for the diagnosis if bilateral opacities are present, although clinicians often order CT to evaluate for alternative causes, such as pulmonary embolism. Patients who present with acute illness may require ventilatory support. Unfortunately, some patients have died. Treatment with corticosteroids seems to be effective. While most patients completely heal, there is little data on the long-term appearance of survivors of EVALI.
Lung Pathology of EVALI
For most cases of EVALI, obtaining lung tissue is unnecessary for establishing the diagnosis, although some literature on pathology now exists. The largest series of cases where pathologic specimens were available was recently published and concluded that EVALI is “a form of airway-centered chemical pneumonitis from one or more toxic substances” in the aerosolized vapor. The presence of lipid-laden macrophages and positive oil-red-O stains has raised the possibility of exogenous lipoid pneumonia due to vitamin E acetate. Regardless of the underlying pathology, macroscopic fat has not been observed on CT imaging.
What Does the Future Hold for Vaping and EVALI?
The recent illnesses and deaths represent a grave tragedy and public health crisis with little precedent. However, it is important for physicians to not focus exclusively on the negative press. Lost in the daily media shuffle is the fact that for some patients, e-cigarettes may be an effective tool for smoking cessation. Recent data from a randomized control trial in the United Kingdom found that nicotine-containing e-cigarettes were almost twice as effective for smoking cessation at one year compared to other forms of nicotine replacement, but the abstinence rate was still only 18.0% (vs 9.9%). Patients in the e-cigarette group also experienced a greater reduction in cough and phlegm production. On the other hand, can patients stop vaping once they have started? At the one-year mark, 80% of the patients using e-cigarettes in this group were still using. Many health officials are worried that it is just replacing one habit (smoking) with a slightly less bad habit (vaping). Vaping might be safer than traditional cigarette use, but at this point, we just don’t know.
Hopefully, the agents responsible for cases of EVALI will be discovered, and cases of acute lung injury will subside, but what are the long-term effects of vaping? Vaping is a new practice that has been around for barely more than a decade, and it is certainly a worry that long-term vaping could lead to more chronic lung disease and fibrosis. We have seen some indication that vaping may progress to fibrosis, although this realm is largely unexplored and ripe for imaging research.
The opinions expressed in InPractice magazine are those of the author(s); they do not necessarily reflect the viewpoint or position of the editors, reviewers, or publisher.