Published On May 27, 2020
FARRAH KHERADMAND WAS PUZZLED by what she saw under the microscope. The slides contained lung tissue, stained purple and red, of mice that had been exposed to the aerosols produced by the “vaping” of electronic cigarettes. In the tissue, macrophages, a type of immune cell, were not only enlarged but also bulging with translucent fats. “There were these glistening, large, abnormal buildups of lipids,” she says. “I was really taken aback—it was unlike anything I’d ever seen in a healthy mouse.”
Kheradmand, a pulmonologist and professor at Baylor College of Medicine in Houston, was investigating with her team whether e-cigarettes are a safer alternative to conventional tobacco cigarettes. It was a question that often came up at Houston’s Michael E. DeBakey Veterans Affairs Medical Center. “I was actually getting cornered in the hallways by vets asking me, ‘Can I switch to vaping? I hear it’s better for you,’ ” Kheradmand says.
That safety argument has helped to attract millions of users over the past decade. Cigarette smoking exposes smokers to scores of chemicals known to be deadly and is linked to one in five deaths annually in the United States, killing about 480,000 people. E-cigarette manufacturers argue that their product, on the other hand, is inherently safer. Users breathe in a vaporized liquid that contains only nicotine, a few solvents and sometimes a flavoring such as menthol or cherry.
Doubts had already taken root about the safety of vaping, and now, as the pandemic spread of a respiratory disease has affected more than 1.8 million people in the United States, the question has become more urgent. The virus that causes COVID-19 preys on the lungs, and although there are few solid data points yet, the National Institute on Drug Abuse has warned that vaping could cause underlying health problems that complicate coronavirus symptoms. Kheradman’s study provides one chilling example. Most vaping mice models who were then exposed to a flu virus—another pathogen that causes respiratory illness—died shortly after.
Kheradmand’s study and other research suggest that vaping weakens defenses in fighting infection and compromises the immune system, says Jonathan Winickoff, a pediatrician and director of pediatric research at the Tobacco Research and Treatment Center at Massachusetts General Hospital. “We don’t have any direct studies yet, but it’s likely vaping increases the risk of severe symptoms and complications in people infected with COVID-19,” he says. The physical act of lifting the vaping device to the mouth may increase the chance of the user becoming infected— “you’re spreading whatever is in your hand into your body”—and an increased need to cough or expectorate could help spread the disease further. Massachusetts has issued a health alert that vaping can exacerbate the risks of spreading COVID-19, and Winickoff expects other states to follow suit.
This isn’t the first—or even the greatest—alarm bell to be sounded about e-cigarettes. In 2019 a shocking number of vaping-related lung illnesses and deaths began to reach the news, and that summer, the Centers for Disease Control and Prevention began tracking cases it classifies as EVALI—for “e-cigarette or vaping product use-associated lung injury.” Before the pandemic, more than 2,800 people had been hospitalized around the country, and as of February 2020, there had been 68 confirmed deaths. Most of those who have gotten sick were 24 or younger.
Youth vaping rates have been on the rise since 2011, and in just one year, from 2018 to 2019, the reported use of e-cigarettes by U.S. middle school and high school students rose from 3.6 million to more than five million, representing 11% of those in middle school and 28% of high school students. The use of the products in that age range alone constitutes a health crisis, as nicotine exposure during adolescence can cause addiction and harm the developing brain, says Nii Addy, associate professor of psychiatry and cellular and molecular physiology at Yale School of Medicine. Studies in young mice suggest nicotine exposure can lead to long-term problems, and because the human brain isn’t fully developed until around age 25, these “may be effects that we see in people down the road,” Addy says. Potential problems include attention disorders, impulse control issues and a higher risk for substance misuse, he says.
In 2018 the U.S. surgeon general declared e-cigarette use among youth “an epidemic,” and there have since been attempts to ban or restrict the practice, and not only for the young. New York state’s Academy of Family Physicians asked for a ban of all e-cigarettes during the entire COVID-19 pandemic, noting that the risks, while still unknown, were potentially great. Measuring the precise nature of those risks remains a task for labs and institutions across the country.
SMOKING A TRADITIONAL CIGARETTE produces more than 7,000 chemicals, 93 of which the Food and Drug Administration has classified as harmful or potentially harmful. But no one knows exactly what chemicals are in e-cigarettes, which come in a range of models and can emit different toxicants. What is known is that vaping devices are becoming more and more powerful, designed to deliver larger aerosol clouds and elevated doses. Users can also modify their devices and the aerosols they vape. The EVALI investigation, for example, has been complicated by the fact that patients reported using so many different products.
“E-cigarette smokers aren’t going to die from the same diseases that cigarette smokers die from because e-cigarettes just don’t deliver those same carcinogens,” says Thomas Eissenberg, professor and co-director of the U.S. Center for the Study of Tobacco Products at Virginia Commonwealth University in Richmond. “But e-cigarettes do deliver things that may be just as toxic.” For example, a 2009 FDA report on the dangers of e-cigarettes noted that scientists, analyzing cartridges from two leading brands, found diethylene glycol, a toxic chemical used in antifreeze, as well as nitrosamines and other carcinogens.
When it issued that report, the agency asked health professionals and consumers to detail serious adverse events from vaping or product quality problems. That information was reviewed alongside other evidence in a 2013 summary by researchers at the University of California, San Francisco. The authors noted that serious health issues and hospitalizations because of congestive heart failure, hypotension, pneumonia and chest pain had been reported to the FDA. “Even that early, there was a fair amount of evidence that e-cigarettes were more dangerous than they looked,” says Stanton Glantz, principal investigator at the UCSF Tobacco Center of Regulatory Science and an author of the review.
But conflicting information also emerged. A 2015 review by Public Health England in the United Kingdom, an agency similar to the CDC, surveyed the opinions of a dozen experts and contended that e-cigarettes are “around 95% less harmful than smoking.” Indeed, U.K. public health officials continue to encourage physicians to promote e-cigarettes to help smokers quit. That “around 95%” estimate, not tied to any hard data, is nevertheless widely cited. “People use that claim as a reason to keep using e-cigarettes,” Eissenberg says. “Or if they’ve never used nicotine before, they hear 95% safer and figure, ‘That’s safe enough for me.’”
A 2018 report from the National Academies of Sciences, Engineering and Medicine evaluated 800 peer-reviewed scientific studies on the human health effects of e-cigarettes. It wasn’t quite as sanguine. Although the report did conclude that e-cigarettes are less hazardous than combustible cigarettes, with a vaper’s exposure to harmful substances “significantly lower” than it would be if smoking cigarettes, the report did note that e-cigarettes generate potentially toxic chemicals, in addition to nicotine. “The report found no evidence of long-term harms to health, but acknowledged that this was based on a limited body of evidence available at the time,” says Nancy Rigotti, director of the Tobacco Research and Treatment Center at MGH, who served on the report’s panel of experts. “And most of the studies reviewed tested earlier generations of devices. I think it’s fair to say the needle has moved since then.”
RECENT RESEARCH SHOWS A much starker picture. In an analysis of 28,000 adults in the Population Assessment of Tobacco and Health (PATH) study, researchers at the University of Rochester in New York found that people who vaped were nearly twice as likely to struggle with wheezing as people who didn’t regularly use tobacco. Wheezing, caused by narrowed or abnormal airways, often precedes other serious health conditions including sleep apnea, emphysema, heart failure and lung cancer.
Another risk comes from the toxic chemicals such as acetaldehyde and formaldehyde—both known carcinogens—that have been detected in e-cigarette aerosols. The metal heating coils in the devices can also cause users to inhale lead, chromium, manganese and nickel, according to a study conducted at Johns Hopkins Bloomberg School of Public Health in Baltimore. And the flavoring compounds are also under scrutiny. E-cigarette makers aren’t required to disclose all of the chemicals they use to flavor their products, but there’s growing evidence that some can be dangerous. “Flavorings were designed for food, and are rarely tested for inhalation,” says Maciej Goniewicz, a toxicologist at Roswell Park Comprehensive Cancer Center in Buffalo and co-director of the Western New York Center for Research on Flavored Tobacco Products, a collaboration between Roswell Park and the University of Rochester Medical Center.
Goniewicz’s team has launched a five-year clinical study that is tracking a group of 100 volunteers who vape. Every month a small bus drives to retail e-cigarette outlets, staffed by a certified phlebotomist and pulmonary function technician who evaluate the users for potential health effects, through metrics that include samples of blood, urine and exhaled breath. They also collect data about the devices and flavorings each person has been using. “Changing flavors is quite common and we want to see how that may affect users’ respiratory symptoms,” Goniewicz says.
Other studies on flavorings home in on two chemicals: diacetyl and 2,3-pentanedione. Known for its buttery aroma, diacetyl is safe when eaten, but in its inhaled form it has been linked to a serious lung disease called bronchiolitis obliterans—also known as “popcorn lung,” because it was first observed in workers at popcorn factories. After that health risk was established, 2,3-pentanedione was sometimes substituted for diacetyl. But studies have shown respiratory injury in rats and mice that inhale either of these chemicals, and researchers at the Harvard T.H. Chan School of Public Health and the University of Pennsylvania recently published a study showing their negative impact on cultured human lung tissue. They also discovered links between the chemicals and chronic obstructive pulmonary disease, asthma and other conditions.
KHERADMAND’S MOUSE STUDY, FUNDED by the National Institutes of Health, was designed to look for a link between vaping and emphysema, a condition caused most frequently by smoking tobacco in conventional ways. In emphysema, lung air sacs become damaged, causing shortness of breath. To test for the effects of vaping, one group of mice was exposed to e-cigarette vapors containing nicotine and two common vaping solvents. A second group received vapors with the solvents but no nicotine. These groups were compared with mice exposed to tobacco smoke or to clean air.
The mice inhaled tobacco smoke or e-cigarette vapors for four months, the equivalent of people who began smoking as teens and continued into their fifties. The mice exposed to cigarette smoke had severely damaged lungs and excessive inflammation, much like human smokers with emphysema. Kheradmand and her team expected to see similar results in the other groups but didn’t find them. Then a team member showed her the slides of the lung tissue from vaping mice that revealed extensive cell damage. “I honestly did a double take,” she says. “Where is this fat coming from?”
Further experiments showed that chronic exposure to e-cigarette solvents alone, without nicotine, was enough to disrupt the basic biology of the mouse lungs. One of the two solvents was vegetable glycerine, a type of fat. But the immune cells hadn’t guzzled the fat directly from the vapor, as Kheradmand initially suspected. Instead, the accumulated lipids came from an abnormal turnover of the lungs’ protective fluid layer—a process that involves macrophages, which essentially went into overdrive in reaction to the chemicals. When researchers then infected this group of mice with small amounts of a flu virus, their weakened ability to battle infection killed most of them.
Kheradmand notes that while her team was working on the mouse study, several reports came in of e-cigarette users developing a form of pneumonia. “The staining of cells within their lungs looked identical to what our mice had,” she says. E-cigarette users could also be more vulnerable to serious illness from COVID-19, she adds. “It’s more important than ever to explore how vaping might make our lungs weaker or more vulnerable to disease, as we face a pandemic that essentially targets that organ.”
Now, Eissenberg is recruiting adult vapers to investigate whether Kheradmand’s findings hold true for humans. “Her study is incredibly important, a stunning finding and potentially a big warning sign about the long-term health effects of e-cigarettes,” Eissenberg says.
WITH POTENTIAL RISKS COMING in from many quarters, regulators have increasingly been called on to come down hard. “We know far less today than we should and we have allowed the e-cigarette industry to conduct basically an experiment on our entire population,” says Matthew Myers, president of the Campaign for Tobacco-Free Kids. In early April, the House Oversight Committee urged the FDA to “clear the market” of e-cigarettes because they might increase the number of serious cases of COVID-19.
Even before the pandemic broke, some tougher laws began to kick in. A statute that took effect in late 2019 raised the federal minimum age for purchasing tobacco products—including e-cigarettes—from 18 to 21. Then in January, the FDA announced a ban on sales of all cartridge-based fruit-, mint- and candy-flavored e-cigarette products. As of September 2020, all e-cigarette makers must submit an extensive application to the FDA with a health and safety review of vaping products they want to remain on the market.
There is still one argument in favor of e-cigarettes—that they might indeed be an effective aid for people who want to stop smoking regular cigarettes. E-cigarettes aren’t approved by the FDA for that purpose, and numerous studies evaluating their effectiveness as a smoking cessation tool show mixed results. Still, some researchers and public health experts believe that vaping offers a net public health benefit if it replaces conventional smoking. If most current U.S. smokers switched to vaping e-cigarettes over the next 10 years, there could be as many as 6.6 million fewer premature deaths and 86.7 million fewer life years lost, according to researchers at New York University School of Global Public Health.
“There’s just incredible disagreement within the public health community over whether e-cigarettes cause more problems than they solve,” says Michael Siegel, a professor at Boston University School of Public Health. He says he believes that overregulation of e-cigarettes could make things worse, with both vapers and former smokers turning to smoking if e-cigarettes are banned.
Against this shifting backdrop of research and regulation, physicians are left to grapple with how to provide care and guidance to adult smokers, users of e-cigarettes and the large numbers of young people now dealing with nicotine addiction as a result of vaping, says Winickoff. He notes that the stay-at-home orders caused many parents to discover their children’s vaping habits for the first time. That led to worried calls about how vaping might put them more at risk for the disease. “There’s plenty yet to learn about vaping and COVID-19, but the time to act on current information is now,” he says. “The good news is that the crisis has created a real opportunity to talk about the dangers—and to help current users to quit.”
“Electonic Cigarettes Disrupt Lung Lipid Homeostasis and Innate Immunity Independent of Nicotine,” by Matthew C. Madison et al., The Journal of Clinical Investigation, September 2019. This study shows how chronic exposure to vaping harms the lung cells of mice.
“Invalidity of an Oft-Cited Estimate of the Relative Harms of Electronic Cigarettes,” by Thomas Eissenberg et al., American Journal of Public Health, October 2019. The authors reexamine the 2013 claim that e-cigarettes are “95% safer” than combustible cigarettes.
“Cardiovascular Risk of Electronic Cigarettes: A Review of Preclinical and Clinical Studies,” by Nicholas D. Buchanan et al., Cardiovascular Research, November 2019. In this review, the authors conclude that e-cigarettes harm cardiovascular health.
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