Doctors and researchers scattered around the globe saw problems, but ‘nobody put two and two together’
Scientists, regulators and e-cigarette proponents missed, ignored or downplayed signs that vaping could significantly damage the lungs for nearly a decade, a review of medical literature, government documents and interviews with doctors shows.
At least 15 incidents of lung injuries linked to vaping occurred prior to this year’s epidemic, a review by Bloomberg News found. The cases — spanning the globe from Guam to Japan to England to the U.S. — include reports of mysterious pneumonia and fatal bleeding from tiny air sacs.
“It’s fair to say that there were early warning signs that were missed,” said Stanton Glantz, a tobacco researcher at the Center for Tobacco Control Research and Education at the University of California, San Francisco. “These cases have been reported for several years but nobody put two and two together because they were too isolated.”
In 2011, a 42-year-old woman arrived at Legacy Good Samaritan Medical Center in Portland, Oregon, with breathing problems, cough and a fever. Hazy white patches resembling ground glass covered about a third of her lungs on chest scans, suggesting extensive inflammation. Strange fat deposits clotted her lungs’ immune cells. After ruling everything else out, pulmonologists concluded she had a form of pneumonia more commonly seen in carnival-show fire breathers or people who have inhaled mineral oil.
Three years later, in northwestern Spain, a man in his 50s surfaced with similar symptoms, and doctors blamed the man’s illness on vaping-induced pneumonia. The incident, which was referenced in a presentation given at a nicotine conference in 2014, according to documents obtained by Bloomberg through a public-information request, was never formally published in a medical journal.
In 2016, doctors in Roanoke, Virginia, reported treating a 27-year-old e-cigarette user who had to be put on a mechanical ventilator because of rapidly worsening breathing problems. In the presentation at a medical meeting that year, the doctors who treated him called his condition “vapor lung.”
U.S. regulators are trying to understand the cause of eight deaths and more than 530 acute lung injuries tied to vaping this year, most of them in recent months. Officials haven’t determined the cause of the outbreak or identified any single product or substance responsible for causing the injuries. At the same time, the vaping industry has been thrown into turmoil. On Wednesday, Juul Labs Inc. said its Chief Executive Officer Kevin Burns was stepping down, and that the company was effectively ending all marketing and lobbying of the Trump administration.
“We don’t know enough about the aerosol that vaping produces” and its health effects, said Anne Schuchat, principal deputy director of the U.S. Centers for Disease Control and Prevention, at a hearing before the House Committee on Oversight and Reform on Tuesday. “It may be that the process itself is risky.”
A Vast Experiment
The new cluster of disease underscores how a debate over the health advantages of e-cigarettes has complicated efforts to understand whether and how inhaling vapor could harm the lungs. As vaping exploded in popularity, scientists and regulators missed hints it might not be as benign as proponents hoped. Focused on whether vaping reduces exposure to cancer-causing compounds in cigarettes, they largely sidestepped key questions about whether e-cigarettes posed entirely new risks.
Doctors and researchers who authored journal articles about their findings, or who attempted to publicize patients’ illnesses, were often attacked on social media, in letters to the editor, or at conferences by vaping advocates and researchers with ties to the e-cigarette and tobacco industries. Others said that they weren’t sure where to report vaping-related illness, given light regulation of the industry. Within the U.S. government, researchers clashed over the safety of vaping, slowing new regulation and opening the chance for e-cigarette companies to expand their reach before a consensus emerged.
“We’re conducting a big, uncontrolled and poorly documented set of chemistry experiments inside people’s lungs,” said Alan Louis Shihadeh, an aerosol scientist at American University of Beirut, part of the U.S.-government funded Center for the Study of Tobacco Products. Researchers “know very little about the safety of it.”
Doctors who treated some of the early cases say it is possible other cases were overlooked. Danielle Hosmer, a pulmonologist and occupational medicine specialist who treated the patient in Portland in 2011, questioned the patient for more than a half hour about possible environmental exposures, including vaping. At the time, she said, most doctors wouldn’t have thought to ask.
“It would be completely easy to miss,” she said. “This has been going on for a longer period of time than people realize.”
While she and her colleagues published the case in a medical journal in 2012 and made efforts to alert other hospitals in Portland, Hosmer didn’t alert federal authorities.
The CDC’s Schuchat told lawmakers that the evidence suggests the disease started to pick up in the spring and summer of this year. “It is less likely that large-scale we have been seeing this and missed it,” she said Tuesday. Schuchat expects the number of reported cases to rise sharply. The majority of cases reported to this point involve vaping of fluids containing the compound THC found in marijuana. Only a minority involve nicotine fluids alone.
The health effects of regularly inhaling the base components of vaping fluid — propylene glycol and glycerin — aren’t fully understood. While the common food additives are deemed safe to eat, heavy vapers are receiving large doses over long periods of time, delivered in ultrafine particles to the deepest parts of the lungs.
“Science has demonstrated that vaping as a substitute for smoking saves lives, and is at least 95% safer than combustible cigarettes,” said Tony Abboud, executive director of the Vapor Technology Association. “That level of harm reduction potential should not be dismissed — especially when combustible cigarettes remain the No. 1 cause of preventable deaths in the U.S.”
E-cigarette proponents and manufacturers have for years been discussing at least the potential of there being adverse health effects from their products. In June 2014, Riccardo Polosa, an e-cigarette researcher and advocate at the University of Catania, in Italy, presented a study at the Global Forum on Nicotine in Warsaw, Poland, titled “Harmful and potentially harmful constituents in e-Cigarettes.”
The presentation, which was contained in a cache of records that Juul Labs handed over to the Food and Drug Administration, mentioned the case in Spain that year in which the man in his fifties was treated at a hospital in the port city of La Coruña for non-respiratory symptoms. Juul first began selling its products in 2015 and hasn’t been connected to the man’s illness.
The man eventually developed a cough and difficulty breathing. After a series of tests, doctors concluded the man’s e-cigarette use had given him lipoid pneumonia.
“Unfortunately we are re-writing history,” said Ana Souto Alonso, a doctor at the Complejo Hospitalario Universitario de A Coruña, where the patient was treated. “With tobacco it took many years to know the toxic effects. Now we’re learning with vaping — we don’t really know the effects on health.”
Polosa, who says he’s received funding for research from Philip Morris International Inc. and e-liquid manufacturers, was among a handful of e-cigarette advocates who cast doubt on the idea that the man’s illness was caused by vaping.
“There is no way vaping could put people at risk for lipoid pneumonia,” Polosa wrote in a March 2014 response to the Spanish case on a website called the “Ashtray Blog.” In an interview, Polosa said at the time that he was asked to review the clinical notes related to the Spanish patient and concluded that his lung illness was linked not to vaping, but to a series of unrelated medical procedures.
The following year, in 2015, a researcher at the National Institute for Occupational Safety and Health warned FDA regulators that two ingredients in some e-cigarette flavorings, diacetyl and pentanedione, had been found to be potentially harmful, according to documents obtained by Bloomberg.
Diacetyl was linked to a 1990s case in which eight workers at a microwave popcorn factory in Missouri developed lung damage after breathing in the chemical, used to give the popcorn a buttery flavor.
“Safe enough to eat does not mean it is safe to breathe,” said the researcher, named Ann Hubbs, according to a copy of a presentation she gave at an FDA hearing on e-cigarette safety.
In written comments, Hubbs’ agency, part of the CDC, warned, “the inhalation toxicity of most flavorings is a major concern that has not been investigated.” The base fluid ingredients “may elicit pathophysiological and/or pathological changes in lung function,” the agency said.
Meanwhile, apparent cases of vaping-related lung injuries continued to appear. In 2015, a 34-year-old woman showed up at Birmingham Heartlands Hospital in England with respiratory failure after using e-cigarettes. Doctors detected fat in her lung immune cells and concluded she contracted lipoid pneumonia from using e-cigarettes. But the case wasn’t published in a medical journal until last year. Gareth Walters, a consulting pulmonologist, said he sent a letter to the maker of the patient’s e-cigarette asking for a list of ingredients, but never received a response.
In 2016, doctors at West Virginia University reported a fatal case of hemorrhage in air sacs in the lungs they attributed to vaping. The same year, one of the doctors in Portland who had treated the 2011 patient saw another pneumonia case in which the patient had spent a prolonged time vaping in her room after fighting with a roommate.
By 2017, scientists who had been exposing lab animals to vaping substances for months started seeing potentially worrisome results.
Researchers at Telethon Kids Institute in Perth, Australia, published a study showing glycerin made the airways of adolescent mice hyper-responsive, as if they were asthmatic. E-cigarette aerosols can cause “significant impairments in lung function,” they concluded. Vaping proponents attacked the study in a letter to the editor, saying various technical problems raised questions about its accuracy.
“Breathing anything into the lungs other than air is probably not going to be good in the long term,” said lead researcher Alexander Larcombe.
In Houston, students of Farrah Kheradmand, a physician researcher at Baylor College of Medicine, had gone to a nearby vape shop in 2016 and asked for the most popular mixture of propylene glycol and glycerin. They then tested it in mice for four months with and without nicotine. They used no flavorings.
In summer 2017, one of her graduate students came to her with an unexpected finding. Key immune cells in their mice appeared highly abnormal — jammed with fat in the same way that the Portland doctors saw in their patient.
“I won’t forget it,” Kheradmand recalls. “In 15 years of doing this, I had never seen anything like this.”
In a study published this month, the Baylor researchers showed that the fat deposits were coming from inside the lungs. Kheradmand suspects that vape solvents disrupt the ability of cells to recycle lung surfactant, an oil-protein substance that is required to keep the air sacs open.
If e-cigarettes were a drug, detailed human studies on their safety would have been performed before they entered the market, said Maciej Goniewicz, a pharmacologist at Roswell Park Comprehensive Cancer Center in Buffalo, New York. But those studies are only beginning to be done now, including a 100-patient lung-safety trial of e-cigarettes he is conducting.
Participants in his study ask about the safety of various vaping products, and whether one product may be safer than another. “It is really hard to give any advice to them,” says Goniewicz.
Robert Langreth and Lauren Etter/Bloomberg