EVALI was the first major outbreak of e-cigarette-related illness, highlighting just how little researchers know about the impact of e-liquids. To make matters worse, the median age of EVALI case patients was 24, which fueled growing concerns over youth uptake of e-cigarettes.
What Is EVALI?
EVALI, which stands for E-cigarette or Vaping Use-Associated Lung Injury, emerged a few years after e-cigarettes became the most commonly used tobacco product among youth in the United States. It was originally known as VAPI (Vaping Associated Pulmonary Illness).
According to criteria from the Centers for Disease Control and Prevention (CDC), EVALI can only be diagnosed if the patient has used an e-cigarette in the past 90 days before the initial symptoms.
Effects of EVALI
Interestingly, there is no single test for EVALI. It is characterized by features that mimic a range of pulmonary diseases and, as a result, the diagnosis process is one of elimination.
A 2020 report analyzed results from 98 EVALI patients, all of whom had reported using e-cigarettes and related products in the 90 days before the onset of the symptoms.
- 97% of patients presented with respiratory symptoms
- 77% of patients presented with gastrointestinal symptoms
- 100% of patients presented with constitutional symptoms
Participants reported a wide range of products, but 89% reported having used THC e-liquids in their e-cigarettes.
Although this report doesn’t provide a conclusive overview of EVALI symptoms, clinicians and researchers use the data to help identify the condition. Alongside the more recognized respiratory symptoms, EVALI can also be characterized by nausea, vomiting, diarrhea, weight loss, and chills.
What Causes EVALI?
Initially, researchers struggled to identify the pathology of EVALI. After assessing the cases of five patients, researchers stated that “based on clinical history, radiography, and laboratory and bronchoscopic diagnostics, a diagnosis of acute exogenous lipoid pneumonia was made for all five patients.”
Although this explanation received a positive reception, a literature review announced that “classic histologic features of exogenous lipoid pneumonia have not been identified” in the tissue samples provided, and the scientific community moved their focus to Vitamin E Acetate.
The Role of Vitamin E Acetate
The cause or causes of EVALI are not entirely clear, but the consensus is that Vitamin E Acetate is closely linked to the condition.
One study from 2021 sought to identify the causative agents of the EVALI outbreak. Researchers collected bronchoalveolar lavage (BAL) fluid from 51 EVALI patients in 15 states and 99 healthy non-smoking participants in an adjacent study into the effects of smoking.
Researchers assessed the fluid for priority toxins, including Vitamin E Acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.
- Fluid from 48 of the 51 (94%) EVALI patients contained Vitamin E Acetate
- Among those EVALI patients who had available laboratory data, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in their BAL fluid or had reported vaping THC products in the 90 days before EVALI symptoms began
- None of the fluids from the 99 healthy patients contained Vitamin E Acetate
- No other priority toxins were found in the EVALI patients or the healthy patients, except for coconut oil and limonene, which were found in one patient from each group
This proved to be a seminal study, leading to further research into the presence of Vitamin E Acetate in e-liquids. Soon after, the FDA concluded that Vitamin E Acetate was the main culprit behind the EVALI outbreak.
What Is Vitamin E?
Vitamin E Acetate is a naturally occurring antioxidant found in vegetables, vegetable oils, seeds, and fruits. In the wider world, Vitamin E Acetate is found in skin creams and multivitamins.
According to Dr. Benjamin C. Blount and his colleagues at the CDC, “The addition of Vitamin E Acetate to product fluid began to appear in the illicit market in late 2018 or early 2019.”
This decision was presumably a combination of convenience and cost-effectiveness. Vitamin E Acetate is easy and cheap to procure and acts as a filler agent in e-liquids, which makes it an attractive prospect for manufacturers of illicit vape liquids.
Soon after manufacturers started adding Vitamin E Acetate to e-liquids, health officials noticed a worrying spike in lung-related issues. The patients had one thing in common: Vitamin E Acetate was found in their lung fluid samples.
How Vitamin E Acetate Impacts Lungs
Like much of the discourse around EVALI, the science of how Vitamin E Acetate impacts the lungs is uncertain.
One theory is that Vitamin E Acetate interacts with pulmonary surfactant (PS) in the lungs.
PS is a phospholipid layer that lines the millions of alveoli (air sacs) in the lungs. The alveoli are responsible for exchanging carbon dioxide with oxygen, allowing us to breathe comfortably. To achieve this, the PS layer has to reduce the surface tension of the alveoli.
Researchers speculate that Vitamin E Acetate disrupts this process. It is lipophilic, meaning it has a nonpolar aliphatic carbon chain that is compatible with PS layers. In theory, the carbon chain inside Vitamin E Acetate could penetrate the PS layer, disrupting the organization of lipid molecules, changing the surface tension, and eventually leading to lipoid pneumonia.
Lipoid pneumonia is caused by inhaling oil-based substances and is characterized by inflammation of the lungs, which can cause any number of lung-related problems, just like EVALI.
The CDC’s Response to EVALI
Faced with an onslaught of seemingly vape-related lung issues, the CDC identified an outbreak of EVALI in 2019. It collected reports from each state via a standardized case report form.
The following statistics have come from the CDC’s archive.
Fatality of EVALI
February 18, 2020. The CDC reports that 2,668 hospitalized EVALI cases have been reported. To make matters worse, sixty-eight deaths were confirmed across 29 states and the District of Columbia.
EVALI Cases By Age Group
January 14, 2020. Among the 2,668 hospitalized EVALI cases or deaths reported to the CDC, the median age was 24.
By age group:
- 15% were under 18 years old
- 37% were 18-24 years old
- 24% were 25-34 years old
- 24% were 35 years or older
The age range spanned from 13 to 85 years.
EVALI Cases By Substance Use
January 7, 2020. Of the 2,668 patients, 2,022 provided data on the substances they used before developing a lung-related injury.
- 82% reported using THC-containing products
- 33% reported exclusive use of THC-containing products
- 57% reported using nicotine-containing products
- 14% reported exclusive use of nicotine-containing products
EVALI Patients Who Used THC Products
January 7, 2020. 50% of the EVALI patients who reported using THC-containing products provided data on the source of the product.
- 16% reported buying products only from commercial sources (vape shops, medical dispensaries, etc)
- 78% reported buying products only from informal sources (friends, online, etc)
- 6% reported buying products from commercial and informal sources
EVALI Patients Who Used Nicotine Products
January 7, 2020. 54% of EVALI patients who reported using nicotine-containing products provided data on the source of the product.
- 69% reported buying products only from commercial sources
- 17% reported buying products only from informal sources
- 15% reported buying products from commercial and informal sources
EVALI Cases Among Adolescents
The EVALI outbreak intersected with ongoing worries about youth uptake. One study found that cases of EVALI have emerged in the pediatric population, with one patient as young as 13. This finding, combined with the fact that the median age for EVALI patients at the time of the 2019 outbreak was 24, caused a resurgence in concerns over youth vaping.
The CDC’s Conclusions
Following a series of internal and external studies identifying Vitamin E Acetate as the main contributor to EVALI, the CDC announced its findings.
Dr. Anne Schuchat, then Principal Deputy Director at the CDC, said, “These findings do not rule out other possible compounds that may be causing lung injuries but help us better understand potential ingredients that may contribute to the cause of EVALI.”
The End Of EVALI Data Collection
September 2019 marked the peak of the EVALI outbreak. After the drastic drop in known EVALI cases, the CDC stopped collecting data in February 2020.
The CDC still monitors EVALI with data from the National Syndromic Surveillance Program’s BioSense/ESSENCE platform. As of now, the data does not indicate that EVALI cases will rise to the level of the previous peak.
The CDC has yet to implement a blanket ban on using Vitamin E Acetate in vape products. Despite this oversight in federal legislation, many individual states and e-cigarette manufacturers have independently banned or eliminated the chemical.
The Future of EVALI
The EVALI outbreak certainly didn’t mark the start of concerns about e-cigarettes, but it acted as a stark reminder that research into the health impacts of vaping has a long way to go. Faced with a condition that mimics other respiratory illnesses, researchers were (and still are) at a loss for a conclusive way to identify the causes and symptoms.
The outbreak also raises questions as to what exactly goes into e-liquids, and whether manufacturers do their due diligence before releasing THC-containing e-liquids onto the market and inserting cost-effective “filler” ingredients into their products.
Given the lack of regulation and transparency around e-liquid ingredients, it’s not unreasonable to assume that we might see something similar to the EVALI outbreak in the future.
