New reasons to worry about e-cigs

Experiments have shown negative biological effects from the flavor chemicals in e-cigarettes.

Experts are worried about e-cigarettes, and they want internists to be, too. Speakers at the annual meeting of the American Thoracic Society, held in Dallas in May, highlighted how the nicotine devices' effects and appeal differ from those of traditional cigarettes.

E-cigarettes carry health risks that aren't yet fully understood because the devices are so new and rapidly evolving, explained Ilona Jaspers, PhD, professor in the departments of environmental sciences and engineering and pediatrics, microbiology, and immunology at the University of North Carolina in Chapel Hill.

The flavoring of e-cigarettes comes from aromatic aldehydes and some may be riskier to inhale than others Image by 6okean
The flavoring of e-cigarettes comes from aromatic aldehydes, and some may be riskier to inhale than others. Image by 6okean

“It's a constantly changing market, so we're always chasing and always behind on the products in terms of testing their toxicity,” she said. “We may not be seeing [chronic obstructive pulmonary disease], but we may be seeing an uptick in new diseases and new clinical phenotypes here.”

One of her major concerns is the flavoring of e-cigarettes. The flavors come from aromatic aldehydes, including isoamyl acetate (banana flavor), cinnamaldehyde (cinnamon), benzaldehyde (almond or cherry), and vanillin (vanilla), and some may be riskier to inhale than others.

“These are naturally occurring chemicals, but they're obviously not intended for inhalation,” said Dr. Jaspers. “When we say they're ‘generally recognized as safe,’ they are recognized as safe as a food product, not as an inhaled product.” It's already been proven that chemicals that are safe to eat can be dangerous when inhaled, she added, offering the example of diacetyl, which causes popcorn lung.

Dr. Jaspers and her colleagues have experimented and found negative biological effects from the flavor chemicals in e-cigarettes. In one study, she exposed immune cells to cinnamaldehyde. “They're not killing the cells, but what they do is basically obliterating the function of these cells,” she said. “Pulmonary macrophages are not able to ingest bacteria anymore. Same for neutrophils.”

Another study she conducted compared changes in immune genes among people who smoke and those who use e-cigarettes. “Cigarette smokers and e-cigarette users had 53 genes that were changed in both groups, but e-cigarette users had another 305 genes that were changed on top,” said Dr. Jaspers. All of the genes were changed in ways that suppressed immune response, she noted.

Other research has shown that immune response (as tested by a live attenuated flu vaccine) was affected more in women who used e-cigarettes than men. And a comparison of bronchoscopies showed that the airways of e-cigarette users have a particular appearance—not full of mucus as in people who smoke, but a redder color than nonsmokers have. “They're not healthy, but they look very different as compared to their smoking counterparts,” she said.

There are also early indications that e-cigarettes might be associated with different medical illnesses than cigarettes. Dr. Jaspers cited recently published case reports of young e-cigarette users who were diagnosed with acute eosinophilic or lipoid pneumonia.

Based on these findings, one of her colleagues used electronic medical records to tally these diagnoses in their state over time. “It basically completely overlays with e-cigarette use in North Carolina. Are those patients e-cigarette users? We don't know. But the way it tracks is really, really striking,” Dr. Jaspers said.

She encouraged physicians to report any cases like these that they see. “If you have a case report where you find a particular phenotype that could be associated with e-cigarette use, please, please write them up,” she said.

Unfortunately, it looks like physicians will have increasing opportunities to see e-cigarette users, according to Harold J. Farber, MD, a professor of pediatric pulmonology at Baylor College of Medicine in Houston.

“Here's really what scares me,” he said. “From the National Youth Tobacco Survey, you see a rapidly escalating level of electronic cigarette use from 2001, when it was about 1.1%, to 2018 data, when you have one in five high school students as electronic cigarette users.”

He predicted that the rate would probably rise further in 2019 and noted that overall nicotine use among youth went up every year except 2016, when it dipped because the FDA ruled that electronic cigarettes couldn't be sold to anyone under the age of 18 years.

“Up until 2010, we had been conquering the tobacco epidemic,” Dr. Farber said. “This is huge.”

Within the overall growth in the market, the JUUL device has made particularly huge gains. “In 2015, JUUL entered the retail market. By November of 2018, JUUL has 76% of the e-cigarette market,” he said.

The product's design may be part of the reason for its success, the experts said. It looks like a USB device and can be charged in a computer's USB port. “Teachers at school have picked this up and handed it back to kids as ‘You've lost your flash drive,’” said Dr. Farber.

It's not the only e-cigarette with a deceptive design, Dr. Jaspers said. She displayed a photo of one that looks like an asthma inhaler. “The only difference between this particular device and the actual inhaler is the little sticker that says albuterol on it,” she said.

Other e-cigarettes look like activity trackers or work as smartphone cases or accessories. “The creativity has gone wild,” she said. In response, she and other antismoking advocates are creating new tools for educating people about the risks. “When I talked to my 16-year-old daughter, asking what can I do to make you and your friends realize that using e-cigarettes is a really bad idea, she said, ‘Mom, you gotta show scary pictures.’”

Following that advice, Dr. Jaspers developed a demonstration in which she places e-cigarette flavorings in plastic dishes and shows the rapid effects. “If they corrode plastic, why do you think this is safe to inhale?” she asked.