When e-cigarettes first appeared on store shelves a few years back, they were marketed as a sleek, discreet technology that could help adult smokers kick a potentially deadly habit.

Flash-forward to 2018, the year the Juul vape device took over three-quarters of the US e-cigarette market. Instead of catering to adult smokers, the e-cigarette industry appeared to overwhelmingly target nonsmoking youth.

Maciej Goniewicz, one of the leading e-cigarette researchers based at Roswell Park Comprehensive Cancer Center in Buffalo, New York, has watched the shift unfold up close: The volunteers who come forward for his e-cigarette studies seem to be getting younger.

“[These are] people who were breathing pure air for a long time and have never smoked tobacco cigarettes, who now have started using e-cigarettes,” Goniewicz said.

He and other researchers around the world are now scrambling to figure out what impact this new habit might have on developing bodies and brains in the long term. And they’re finding that e-cigarettes may be more dangerous than we’ve appreciated, especially for hearts, lungs, and brains. There’s also a growing body of research suggesting that vaping can lead to smoking.

But before we dive into the latest health concerns, a couple of notes of caution. The new evidence doesn’t mean cigarettes are safer than e-cigarettes. In fact, medical experts agree that vaping is far better for health than smoking, one of the deadliest habits known to humankind. (And that message about relative risk appears to be getting lost, as more and more people erroneously believe e-cigarettes are as or more dangerous than tobacco.)

What’s more, since people haven’t been vaping for very long, the science on the health effects is still preliminary — and far from conclusive. It may take decades for any diseases possibly caused by e-cigarettes to fully surface, particularly in the young, healthy people now using them.

There’s also the problem of making generalizations about e-cigs: There are hundreds of devices on the market, and each one delivers different levels of nicotine (or no nicotine at all) and a slightly different combination of chemicals.

With these caveats in mind, I asked researchers to share what worries them most. Here’s what they told me.

Vaping may be linked to a heightened risk of seizures

When you turn on an e-cigarette, you’re heating a liquid that contains flavors and other chemicals, and often nicotine.

Some devices, in particular Juul, deliver astoundingly high doses of nicotine. (Juul says one of its e-liquid pods is equal to a pack of cigarettes in terms of nicotine.)

The Food and Drug Administration has been warning that nicotine-induced seizures could be a rare side effect of vaping. Over the past decade, there have been at least 35 reports of seizures — sudden and uncontrolled disturbances in the brain — following e-cigarette use. The cases were reported through the FDA’s adverse event reporting system, a database of voluntary reports from patients, product manufacturers, and health professionals, and to poison control centers across the country.

“While 35 cases may not seem like much compared to the total number of people using e-cigarettes, we are nonetheless concerned by these reported cases,” FDA’s former director Scott Gottlieb said in a press release. “We also recognize that not all of the cases may be reported.”

Researchers have long known that seizures can be a side effect of nicotine poisoning — recognized as a risk in agricultural workers who handle tobacco leaves, and in toddlers who accidentally swallow e-cigarette liquid.

Gottlieb warned that it’s not yet clear from the FDA’s reports that vaping caused the seizures. For example, there was no easily identifiable pattern of use linked to the side effect: While some of the cases involved first-time users and just a few puffs, others happened in experienced users after more prolonged exposure. A few cases also happened in people with a history of seizure diagnosis, and in users of marijuana or amphetamines.

The agency also wasn’t able to determine whether a particular brand or type of e-cigarette was most likely to be implicated, since many of the reports lacked that data. (Though it is notable that some devices, in particular Juul, deliver very high doses of nicotine.)

So the FDA is calling for more investigation into whether there is a connection, and asking doctors and the public to come forward if they know about cases.

The nicotine in e-cigarettes may stress the cardiovascular system

There are also nicotine’s heart health concerns. “Nicotine [in e-cigarettes] does the same thing as [combustible] cigarettes,” said Neal Benowitz, a professor of medicine at the University of California San Francisco who’s been studying the link between e-cigarettes and heart health. It can increase the adrenaline circulating in our bodies and activate the sympathetic nervous system (our “fight or flight” response), raising blood pressure, speeding up the heart rate, and causing the arteries — the vessels that carry blood — to narrow.

In January 2018, the National Academies of Sciences, Engineering, and Medicine in its assessment of the evidence on the health impact of vaping determined that there was “insufficient” evidence that e-cigarette use leads to long-term changes in heart rate and blood pressure.

But Goniewicz told Vox that’s rapidly changing. E-cigarettes’ impact on the body’s cardiovascular system is an emerging area of research, with more studies piling up to suggest vaping could in fact be bad for the heart.

For a June 2019 study published in the Journal of the American College of Cardiology, researchers exposed human endothelial cells — which line the blood and lymphatic vessels — to six e-liquid flavors with different levels of nicotine. They discovered that the e-liquid damaged the cells, exacerbating “endothelial dysfunction, which often precedes cardiovascular diseases.”

In a review of the literature, for the Nature Reviews Cardiology journal, Benowitz and his co-authors made the case that while we don’t yet know what that means for long-term health outcomes, it’s certainly possible nicotine in e-cigarettes will also contribute to cardiovascular events, “particularly in people with underlying cardiovascular disease.”

Several recent observational studies uncovered a link between regular vaping and an increased risk of heart attack, stroke, and coronary artery disease. The studies don’t prove e-cigarettes cause these conditions, but given the known cardiovascular effects of nicotine, there’s likely a lot more to learn about vaping and its effect on these diseases.

The microscopic particles e-cigarettes emit have been linked to heart attacks, high blood pressure, and coronary artery disease

Even when vapor is nicotine-free, it may carry other heart health risks. The heating element in e-cigarettes emits tiny particles, sometimes including metals, which can lodge themselves deep into the lungs and get absorbed into the body’s circulatory system. “That’s where we see the potential cardiovascular toxicity,” Goniewicz said.

Recent studies have shown that puffing on e-cigarettes increases concentration of these microscopic pollutants — in particular, PM2.5 and ultrafine particles — in indoor environments.

Researchers don’t yet know what risks e-cigarette aerosol particles carry, but these tiny particles have been studied extensively in the context of air pollution and tobacco smoking. In those studies, researchers have linked exposure to small particles with a range of bad cardiovascular outcomes, including heart attacks, high blood pressure, and coronary artery disease.

The thinking is that when we’re exposed to large particles, like dust, our bodies mount a defense against them. Namely, we cough, kicking these foreign pollutants out of our respiratory tract. But with fine particulate matter, that defense mechanism doesn’t kick in — and, again, these micro-contaminants can seep into our lungs and cardiovascular system.

Same goes for other toxic chemicals e-cigarettes produce when they’re heated, such as acetaldehyde, formaldehyde, and acrolein.

“We already have sufficient evidence from hundreds of studies that link exposure to those chemicals with disease outcomes,” Goniewicz said. “We know that formaldehyde can cause cancer and that acrolein can cause certain cardiovascular diseases.” So there’s no conclusive evidence directly linking this aspect of e-cigarette use to long-term cardiovascular outcomes. But based on these studies, researchers believe such a link is plausible.

E-cigarette vapor may irritate the lungs

Much of the harm caused by tobacco smoking comes from the combustion process — smoke wears down the cells lining the lungs, damaging them and making them more penetrable to the irritating, cancer-causing chemicals in cigarettes. Since electronic cigarettes don’t burn tobacco, the vapor they produce is thought to be much less harmful than conventional cigarette smoke. But that doesn’t mean vapor is harmless.

Breathing vapor into the lungs can irritate them, which has been demonstrated in recent research on wheezing. Wheezing — that high-pitched sound caused by narrowed and abnormal airways — is more than just an annoyance: It can be a sign of emphysema, heart failure, and lung cancer.

Researchers recently tracked 28,000 adults to tease out whether e-cigarettes exacerbate wheezing. Some of the people in the study were current vapers who used only e-cigarettes; others were smokers only; still others were dual users (who smoked and vaped); and finally, there were also folks who didn’t smoke or vape at all.

Compared with that last group, the non-users, the risk of wheezing among the vapers nearly doubled.

When the researchers looked at the study participants’ history of vaping or smoking, they came to even more interesting findings: The risk of wheezing was higher in current vapers who were also ex-smokers than in ex-smokers who did not vape. In other words, it wasn’t just a vaper’s potential history of smoking that was driving the uptick in wheezing among vapers. “Therefore,” the authors concluded, “promoting complete cessation of both smoking and vaping will be beneficial to maximize the risk reduction of wheezing and other related respiratory symptoms.”

Other studies have focused on whether e-cigarette users are more likely to develop chronic obstructive pulmonary disease (COPD), a set of lung complications that make it hard to breathe. Research in mice and human airway cells showed that nicotine-containing e-cigarette vapor seemed to trigger “effects normally associated with the development of COPD.”

In preliminary human studies, researchers also found associations between regular vaping and COPD. But again, this human research was observational, not experimental, so it’s not yet clear that vaping caused COPD. (For example, it’s possible the people who have COPD are more likely to use electronic cigarettes, such as ex-smokers seeking a harm reduction method.)

Still, Benowitz said, “you don’t want to put stuff in your lungs that could cause lung inflammation. My biggest concern about e-cigarettes is that if you’re not a cigarette smoker, they could potentially aggravate asthma, cause a cough, and increase the risk of respiratory tract infection — like cold, flu and bronchitis.”

The devices can explode

There are also more immediate potential e-cigarette harms. A recent New England Journal of Medicine case study described a 17-year-old Nevada teenager who showed up in the emergency room after a VGOD e-cigarette exploded in his mouth “He had a circular puncture to the chin, extensive lacerations in his mouth, multiple disrupted lower incisors, and bony incongruity of the left mandible,” the doctors who treated the boy wrote in their report.

According to the New York Times, the doctors believe the device’s battery caused the explosion. “This technology hit the market by storm and people are not aware,” Katie W. Russell, a pediatric surgeon at the University of Utah and author on the report, told the Times. “But the fact is they can burn you. They can explode in your pocket. They can explode in your face. I think there’s a health concern.”

The FDA has warned that while these explosions are rare — they can happen, and lead to serious injury. One analysis estimates there were 2,035 e-cigarette explosion and burn injuries at US emergency rooms between 2015 and 2017. A smaller study of e-cigarette explosion patients who showed up in Seattle’s University of Washington Medical Center counted among the most common injuries flame burns, chemical burns, and blast injuries. One fifth of patients wounded their faces, 33 percent had hand injuries, and 53 percent had thigh or groin injuries.

Does vaping help people quit smoking or lead to more smoking?

We still don’t know for sure whether the rise in vaping is leading to fewer adults smoking tobacco. The best available research on the question was published earlier this year in the New England Journal of Medicine. The randomized trial on e-cigarettes showed people who were randomly assigned to use e-cigarettes quit smoking at almost double the rate of people who were randomly assigned to nicotine replacement therapy.

But while e-cigarettes performed better than nicotine replacement therapy in the study, they only helped a minority of participants in the vaping group quit.

On the other hand, there is strong evidence that e-cigarettes may act as a gateway to traditional cigarette smoking among youth. The National Academies of Sciences, Engineering, and Medicine report on the health impact of e-cigarettes assessed 10 high-quality studies on this gateway question, and they all pointed to the same effect.

“The evidence base was large enough and consistent enough and strong enough to conclude that there’s an association between e-cigarette use and ever-use of combustible tobacco [cigarettes],” said Adam Leventhal, a member of the report committee, in January 2018. But what’s less clear is whether young people are just more likely to try cigarettes after vaping, or whether they then go on to become long-term smokers.

Either way, this is a very important finding because another key question about the introduction of e-cigarettes to the market has been what impact they’ll have on youth smoking rates, which have dropped precipitously in recent years. Right now, like many e-cigarette health questions, we don’t know the results for certain. But it’s probably time we start paying attention to the possibilities.

Listen to Today, Explained

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