14 October 2022

What is "vaper disease"?

Where did it come from and what we don't know about it

Alexandra Vasilyeva, Mikhalina Akulova, N+1
For links, see the original article.

In 2011, a 42-year-old woman was admitted to the Good Samaritan's Legacy Medical Center in Portland, who had been trying to cure fever, shortness of breath and cough for seven months. She repeatedly went to the emergency department — there she was prescribed antibiotics, but the symptoms did not go away. Doctors prescribed a CT scan and found darkening in the lungs of the "frosted glass" type. And on the walls of the lungs — as they found out by taking mucus samples with the help of a probe — there were macrophage immune cells filled with lipid droplets.

The patient told doctors that the symptoms appeared when she started smoking electronic cigarettes. Then she was diagnosed with "lipid pneumonia", considering the cause of the disease to be glycerin-based oil in electronic cigarette vapors. Eight years later, the United States was covered by a whole outbreak of similar pneumonia: symptoms were found in smokers across the country,

and several dozen people died from it. But doctors still don't know if they diagnosed them correctly and why a woman from Portland actually got sick — and three thousand more vapers followed her.

A drop of oil kills

The first lipid pneumonia was described by a young pathologist George Franklin Laughlen in 1925, when no electronic cigarettes existed.

The doctor studied the case of a two-year-old girl who had diphtheria, immediately caught scarlet fever, and then also ulcerative filmy sore throat. Then sepsis — and as a result, her body ended up on Laflin's dissection table. At the autopsy, the medic saw a lot of reddish-gray nodules in the lungs of the deceased — the usual traces of bronchopneumonia. But Laflin's attention was attracted by the liquid released on the sections of the damaged alveoli. It contained cells with many drops of transparent liquid inside.

"There were so many droplets in some cells that the shape of the cells was distorted and they looked very swollen <...> Their nuclei were shifted to the side or flattened," Laflin described what he saw in his article for the American Journal of Pathology. He determined that these were immune cells (now we call them macrophages), and the liquid in the drops turned out to be oil.

Two days later, Laflin again saw oil droplets in the cells — this time in the lungs of a girl who died of bronchopneumonia. The doctor found the third case in the archive of autopsy reports conducted in the same year. All the children suffered from different diseases and died from different causes. The only thing they had in common was a runny nose. Or rather, the remedy with which he was treated: large — about two grams daily — volumes of drops based on the mineral oil albolene with the addition of menthol.

For the fourth time, Laflin found macrophages filled with oil and signs of bronchopneumonia in a girl who died in a diabetic coma. She did not use drops, but two days before her death she took about seven milliliters of mineral oil as a laxative.

The fifth case was no longer a child, but a 37-year-old man. He suffered from multiple paralysis, and he was also given a laxative — 45 milliliters of vaseline oil three times a day. He also died of bronchopneumonia, and in the lungs there were not only cells familiar to Laflin, but even individual drops of oil.

To confirm his suspicions, Laflin tried to cause the same disease in rabbits. He injected mineral oil with menthol into the trachea or through the mouth of the animals — and after a while the rabbits also died, and the pathologist saw immune cells with drops in the alveoli at the autopsy.

So Laflin was convinced that he was facing a new type of pneumonia, and called it "oily". This diagnosis still exists, however, now the disease is called fatty or lipid pneumonia — and the list of its causes and victims has become much wider.

How they risk

A hundred years later, children still suffer from lipid pneumonia - as well as the elderly and people with neurological disorders. It can be difficult for all of them to swallow, which means that it is more likely that medicines for colds or constipation based on oils will get into the respiratory tract — the same ones that aroused suspicion in Laflin.

Practitioners of lipid pneumonia still meet infrequently. Pulmonologist Vasily Shtabnitsky, in a conversation with N+1, says that he made this diagnosis only once. The patient was neither an elderly man nor a child, but he had an unusual passion — his house was filled with diffusers that sprayed aromatic oils.

"CT showed a small bronchopneumonia,— recalls Shtabnitsky. — The symptoms were also nonspecific: cough, fever and, it seems, chest pain. Staphylococcus was also sown in the patient (that is, it was found in bacterial culture — approx. N+1), that is, a bacterial infection joined the lipid pneumonia. I prescribed antibiotics and advised not to use aromatic oils anymore."

But there is a group of people for whom lipid pneumonia has become an occupational disease — these are fire swallowers. In their performances, they not only inhale, but also exhale fire. To do this, you need to keep an oily flammable liquid in your mouth: it is spat out on a lighted stick held up to your mouth, the liquid ignites and it seems that the fire comes right out of the magician's lungs.

"If you choke at this moment, the liquid will get into the lungs," says Alexander, a breather (as fire swallowers call themselves) with four years of experience. — During training, breezers learn to control breathing so that at the moment of a long exhalation there is no desire to inhale. It is also important to monitor the direction of the wind when you blow the aerosol — do not inhale if the cloud is coming at you. In this case, you need to cover your face, turn away and only then inhale."

Those who hurried to inhale, after a few hours can pay for their mistake. So, Finnish doctors in 1987 and 1989 treated young fire swallowers who were hospitalized after they could not perform this trick cleanly. The doctors saw on their tomograms the same thing that Laflin described, and gave this picture a name — "the lung of the fire swallower".

Internal oil

But it also happens that macrophages are choked by the body's lipids without any external influences.

So, in July 2005, a 63-year-old woman was admitted to the Augsburg University Hospital. The doctors were already familiar with the picture: the alveoli were filled with fluid, and inside it were macrophages with lipid droplets. Doctors did not think long about the diagnosis — although the patient assured that she did not swallow mineral oils and did not abuse drops from a runny nose. So, lipid pneumonia must have some other internal cause.

The patient's blood test showed elevated levels of phosphatase and gamma-glutamyltransferase — signs of problems with the bile ducts. The concentration of total cholesterol also turned out to be one and a half times higher than normal. Therefore, the doctors assumed that the events unfolded as follows: at first, the inflammation damaged the walls of the biliary tract. Through these gaps, cholesterol, the precursor of bile acids, got into the blood. Through the vessels, he reached the lungs, and there macrophages began to work on him.

This is how endogenous lipid pneumonia usually begins. The reasons may be different: sometimes they are problems with the bile ducts, and someone has lung damage (for example, with a tumor or rheumatoid arthritis), as a result of which cells die and fill the alveoli with the remnants of their membranes. The result is the same: macrophages come to the rescue, which absorb lipids, "choke" them and die, only increasing inflammation.

Steam pneumonia

In 2011, Portland doctors got a patient with a seven-month cough and macrophages with oil drops in her lungs. The doctors coped with the diagnosis instantly, but the cause of lipid pneumonia did not become clear immediately.

The woman did not swallow fire and denied that she could inhale any oils or aerosols. Although two weeks before her hospitalization, for example, bedbugs were poisoned at her home. In addition, the patient's medical history included asthma, fibromyalgia, schizophrenia and hypertension. In total, she took more than ten medications.

 But doctors decided that electronic cigarettes were the main culprit of inflammation. Although they had never met such a cause of the disease until then, they knew that pneumonia could develop when inhaling hemp oil vapors — and decided that their patient had suffered because of something similar.

In an article describing this case, Portland doctors warned: electronic cigarettes can be dangerous not only because of nicotine, but also because of its delivery system to the lungs.

And their suspicions were quickly confirmed. Over the following years, doctors described several more cases of lipid pneumonia in vapers. And then the flash started.

In June 2019, five teenagers with shortness of breath, weakness and low blood oxygen were admitted to a children's hospital in Wisconsin. CT showed darkening in the lungs by the type of "frosted glass". Two required intubation and artificial ventilation of the lungs. All of them had a habit of smoking vape.

The hospital reported this to the Wisconsin Department of Health, and he sent a description of the syndrome to other clinics. By the end of August, there were 116 similar cases, and a month later there were already 908. Most patients needed hospitalization. By February 2020, epidemiologists counted more than 2.8 thousand cases and 68 deaths.


Confirmed and suspected cases of lung injury associated with vaping in the USA. Yulin Hswen, John S. Brownstein / New England Journal of Medicine, 2019.

The syndrome was called EVALI — lung injury associated with smoking electronic cigarettes and vaping (E-cigarette and Vaping use-Associated Lung Injury). Unlike classical lipid pneumonia, it mainly affected young people — most of the patients were under 35 years old, two-thirds of them were men. Approximately 22 percent also had asthma. The deceased patients with EVALI were more likely to have concomitant diseases — lung diseases, heart diseases, depression. Many researchers have assumed that EVALI is the same exogenous lipid pneumonia, the scourge of fire swallowers and oil lovers, just in severe form.

But the further we went, the more counterexamples arose to this hypothesis. For example, in some patients, doctors noticed uncharacteristic digestive problems for pneumonia: nausea, vomiting, diarrhea, abdominal pain. And respiratory symptoms, according to some researchers, looked unlike exogenous pneumonia — it proceeds more sluggishly. In addition, the very fact that macrophages with lipids are present in the lungs does not mean that these lipids have entered the body from the outside. In the same way, they can appear in endogenous pneumonia. And if the lipids that macrophages choked on have an internal origin, then it means that this is not necessarily related to vaping.

Finally, to this day, no one has understood what kind of oil (and is it oil?) damaged the lungs of people with EVALI.

What do they breathe

In 2014, a group of American researchers estimated that 466 brands and 7764 flavors were represented in the English—speaking segment of the e-cigarette market alone - thousands of chemicals mixed in a wide variety of proportions. It is not an easy alignment to find the culprit — and this is not taking into account narcotic substances and self-prepared vaping mixtures.

First of all, the suspicion of doctors fell on electronic cigarettes with cannabis oil — 80 percent of patients with EVALI smoked them. Most often, patients used already refilled cartridges of the Dank Vapes brand, under which the online store of the same name distributes products containing tetrahydrocannabinol. There is no centralized production or a clear distribution network for these cartridges — which means they are produced artisanal. Therefore, there was an assumption that the cause of EVALI lies not in the practice of inhaling "electronic vapors", but in violations at the stage of production of mixtures.

The composition of THC mixtures differs from more traditional nicotine mixtures, since cannabis is poorly soluble in propylene glycol or glycerin, which are used as a basis for "refueling" vapes. Therefore, for example, vitamin E acetate is added to them — and in one of the studies, this substance was found in the lungs of 48 out of 51 patients with EVALI. There are suggestions that it can damage the surfactant film lining the alveoli and bronchial tree. Or that it breaks down into toxic derivatives when heated, which cause cell death, as a result of which the alveoli are filled with lipids. Finally, vitamin E itself refers to lipids, so macrophages could simply swallow it and thereby start inflammation.

But these hypotheses have not yet been confirmed experimentally, and therefore vitamin E acetate remains only a suspect, and doctors are testing other substances. So, nicotine could also be the culprit — it was in the composition of electronic cigarettes, which were smoked by up to 50 percent of patients with EVALI, and two-thirds of them found it on flushes from the lungs. However, nicotine was also found in samples of people without EVALI who smoked tobacco or "vaped". This means that nicotine-containing vaping liquids do not necessarily directly affect the lungs.

In addition, if you look at the studies conducted before the EVALI outbreak, there is a lot of evidence that a variety of substances can be dangerous to the lungs — and many of them can get into the vaping mixture, and the device itself can become their source. For example, the composition of almost all mixtures includes propylene glycol or glycerin (often both) — to make it easier to form steam, and inhalation of propylene glycol can cause irritation of the respiratory tract. Also, the flavoring agent diacetyl is often found in liquids, which gives the mixture the smell of oil — and it was once already called a possible cause of bronchiolitis in workers at factories producing popcorn. And also particles of metals that are contained in the evaporator can get into the aerosol: tin, iron, nickel, lead, chromium.

There are not enough experimental data for some substances. Some are not found in all varieties of mixtures and therefore look "less guilty". Perhaps the situation would be clarified by tissue samples from patients — but there is practically no data on autopsies and biopsies. And in those cases when they were still carried out, it is not always easy to distinguish lipid pneumonia from other lung tissue damage.

Without waiting for the final verdict of scientists, the American regulator published a list of EVALI symptoms for medical practitioners. Macrophages with lipid droplets and other signs of lipid pneumonia were not included in this list. To make this diagnosis, it was enough to see the "frosted glass" type of darkening on CT scans, make sure that the patient had been smoking electronic cigarettes for the last 90 days — and not find any other pathologies in him: infections, cardiovascular, rheumatological, oncological diseases. So the diagnosis of EVALI is made from the opposite — the last option in cases where a set of symptoms does not pull on any of the understandable diseases.

Was there a syndrome

Three years later, the description of EVALI has not become more accurate. "Someone develops hypersensitive pneumonia, someone has bronchiolitis or lipid pneumonia, the options for lung damage are quite diverse," says Svetlana Chikina from the University of them. Sechenov. The fact that doctors see such different symptoms in patients may mean that the development of the disease depends on what kind of mixture a person smokes and how often he does it. According to Chikina, the variation in symptoms can be explained by the state of the patients' immune system. Or maybe EVALI is not a single disease at all, but a set of symptoms that can appear for various reasons.

Doctors probably won't be able to say anything more precise in the near future. If only because it is difficult to collect reliable statistics on EVALI cases. For example, it is quite possible that the current list of patients with EVALI includes people with the most pronounced symptoms — those who needed the help of doctors and hospitalization. If we assume that the lung injuries associated with vaping may be different in severity, then the "light" cases of EVALI could go unnoticed. In addition, in trying to find the culprit of the disease, many researchers were based on surveys of patients with EVALI — but people could be wrong (not everyone knows what substances are included in electronic cigarettes) or choose a socially acceptable answer.

Now the outbreak of the mysterious disease has come to naught — or, perhaps, has gone underground. With the arrival of covid, it became even more difficult to diagnose EVALI. The symptoms of these diseases are similar — inflammation, fever, shortness of breath, cough, and a "frosted glass" is visible on the CT scan of the lungs. Therefore, in 2020, a considerable share of EVALI could simply move to the covid statistics. As a "rule of thumb", doctors suggested distinguishing them by the age of patients: people with EVALI are usually young, and severe forms of covid are more common in the elderly. But this criterion, of course, does not improve the accuracy of EVALI diagnostics, which is already moving away from the opposite.


The number of EVALI diagnoses made in the United States from June 2019 to July 2020. Sean J. Callahan et al. / CHEST, 2020.

Anyway, since February 2020, the American CDC has stopped keeping nationwide records of cases. The data was published by local authorities at one time, and then EVALI completely disappeared from the news. Since mid-2020, only retrospective works have been published about her.

However, in August 2021, users of "Public Services" received a newsletter in which they were warned against smoking electronic cigarettes and told about the symptoms of EVALI. The reason, apparently, was the diagnosis that the doctors of the Morozov Children's Hospital made to a 17-year-old teenager. As Pavel Berezhansky, head of the pulmonology department of this hospital, told N+1, "the patient smoked a lot — he did not let the vape out of his hands. Two weeks before his hospitalization, he had a cough, his temperature rose, shortness of breath began to increase: at first it was hard to run, after 2-3 days — to climb to the fifth floor, then to the second, and then to sleep in a horizontal position."

According to Berezhansky, 80-90 percent of the teenager's lungs were affected. He needed oxygen support: about 10 liters of supplemental oxygen per day — as well as anti-inflammatory and hormone therapy. But the doctor's prognosis is optimistic: "Lung function is gradually recovering," he says. — Fortunately, the lungs grow up to 21-22 years, I think most of them will recover."

This teenager remains the first and only case of EVALI in Russia so far. Russian doctors have not heard about other such patients, and there have been no official reports either. Why this happened a year and a half after the outbreak in the United States and whether it was directly related to e-cigarettes is still unknown. Representatives of the Ministry of Health did not respond to the request of N+1 about why letters about EVALI were sent to users of "Public Services".

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