E-cigarettes, Juuls and Heat-Not-Burn Devices: The Science and Regulation of Vaping

In 2014, Oxford Dictionaries selected vape as their word of the year. Their selection reflected the sudden stratospheric popularity of electronic cigarettes, with readers 30 times more likely to encounter vape in news media that year than they were just two years before. Nowhere was their popularity more swift—and alarming—than with young people. As many as one in four teens have tried e-cigarettes, and children as young as 12 are now more likely to vape than they are to smoke. 

“When we first started tracking e-cigarettes in 2008, we saw no uptake, no uptake, no uptake … then there was this huge jump and they suddenly were everywhere,” says Ryan Kennedy, PhD, an assistant professor in Health, Behavior and Society and a faculty member in the Institute for Global Tobacco Control.

For public health scientists, this has meant embarking on a quest to understand the potential health risks associated with vaping in order to inform both e-cigarette users and policymakers. Ranging from cigarette look-alikes to sleek, USB-rechargeable devices, e-cigarettes all heat a liquid to create an aerosol or vapor that users inhale. Early advertisements touted e-cigarettes as a safe alternative to traditional tobacco cigarettes because they didn’t expose users to harmful combustion byproducts. Scientists in the U.K. and Europe have begun to think of e-cigarettes as a way to reduce the harms from cigarette smoking. But a recent spate of studies reveals that vaping may not be as safe as many public health officials hoped. Dangers ranging from flavorings in the e-liquids to metals in the heating coil may cause long-term health effects. Even if vaping proves safer than smoking, that’s still a long way from a gold stamp for their safety, according to Ana María Rule, PhD ’05, MHS ’98, an assistant professor in Environmental Health and Engineering.

Recent work by Rule and other scientists published in Environmental Health Perspectives in February found high levels of heavy metals in many e-cigarette aerosols, including arsenic and cadmium in some of the samples. This and other research is creating a more nuanced picture of the potential hazards of vaping that will influence how the FDA decides to regulate e-cigarettes.

SMOKE AND MIRRORS

In 2003, Chinese inventor Hon Lik filed a patent on the first modern electronic cigarette, which acquired the nickname “cig-alike” due to its superficial resemblance to the real thing. By 2006, e-cigarettes had arrived in Europe and the U.S. Within just a few years, their popularity boomed, thanks to what Kennedy calls “clever, effective advertisements” and celebrity placements. In 2010, vaping revenues in the U.S. alone were estimated at $416 million. By 2015, that number had soared to $3.2 billion. Market projections estimate that the global e-cigarette market will be worth upward of $44 billion by 2024. 

The devices are especially popular with two different groups: smokers trying to quit and young people who have never used conventional cigarettes. The multitude of flavored e-liquids—from grape to vanilla to coffee—are especially appealing to young taste buds. Cartridges of refill liquid can contain high concentrations of nicotine, the rough equivalent to a pack of cigarettes for some products.

 “They are likely safer than continuing to smoke combustible cigarettes, but without the long-term studies, we just don’t know,” says Joanna Cohen, PhD, MHSc, Bloomberg Professor of Disease Prevention and IGTC director.

More than four centuries passed between the global spread of tobacco by Europeans and the definitive research showing that smoking causes cancer and other health problems. E-cigarettes have been around for only 15 years, and it takes at least 20 years of regular use for many chronic health problems to appear, Rule says. Nor is it clear exactly what types of problems researchers should look for.

Rule’s background in environmental engineering and air pollution assessments, however, gave her an advantage. In her time at the School, Rule had built two labs: one to measure nicotine in cigarette smoke, and one to measure heavy metals. In 2013, she was in the process of measuring the tiny particles inhaled by users of hookahs and water pipes when a colleague asked her, “Did you know many e-cigarettes use a metal coil to heat the liquid?”

To Rule, that sparked an immediate concern. The heating coil could leach metals into the liquid that is vaporized and inhaled. A number of metals can be used to create the alloys and solder used in the various parts of the metallic coil, although the most popular coils use nickel and chromium. What’s more, many e-cigarettes are manufactured overseas, where regulations and oversight may be more lax than in the U.S. In 2015, Rule received a grant from the state of Maryland with funds from the Cigarette Restitution Fund to study 58 adults who regularly use e-cigarettes, obtaining urine, saliva and exhaled breath samples, along with samples of the vapor produced by their devices. This provided her the perfect opportunity to study both e-cigarettes and biomarkers in their users.

Rule’s lab had the right equipment to determine whether the inhaled vapor contained harmful heavy metals. But measuring compounds directly from the aerosol emitted from the e-cigarettes was more difficult than Rule anticipated. Postdoc Pablo Olmedo, who had a chemistry background, built a large apparatus to sample the vapor. “I worked on it for more than a year, and I still couldn’t get the vapor to condense,” he says.

Eventually, Olmedo built a small portable sampler made from rubber tubing and pipette tips that captured tiny droplets of aerosol. Using mass spectrometry, the team measured the amounts of 15 different metals in the vapor, as well as in the e-liquid before it contacted the coil. The results shocked Rule. More than half of the samples had concentrations of chromium, manganese, nickel and lead that were higher than recommended health and safety levels. One in 10 samples contained arsenic.

There might be a reduction in risk to smokers if they switch to e-cigarettes, but we don’t know for sure. There are also many, many people vaping who never would have smoked.

“I was expecting to find nickel and chromium, but I was surprised to see lead and arsenic. There is no reason why they should be there,” Rule says. 

Although vapor samples tended to contain higher metal concentrations than the unheated e-liquids, the liquids weren’t metal-free, and Rule admits she has no idea how the metals got into the liquid in the first place. A separate study in Environmental Research in November 2017 found correlations between the concentration of nickel and chromium in vapor and the amounts detected in users’ urine, saliva and breath. In a future study, Rule and colleagues want to see the extent to which e-cigarette vapor contributes to overall heavy metal burden in humans in order to determine its clinical significance.

“There might be a reduction in risk to smokers if they switch to e-cigarettes, but we don’t know for sure. There are also many, many people vaping who never would have smoked,” Rule says.

STRIKING THE RIGHT BALANCE

Cohen, Kennedy and others now must translate the results from Rule’s lab and others around the world into recommendations for policy that will balance e-cigarettes’ potential benefits as stop-smoking aids with their risks. The long-term consequences remain uncertain. And a new study from scientists at the University of Pittsburgh found that half of teens who had vaped for more than 18 months switched to tobacco cigarettes during the study period.

What’s not clear, Cohen points out, is whether those kids would have started smoking even if they didn’t vape, whether e-cigarettes are causing additional young people to take up tobacco products or even whether teens who might have smoked instead stuck with vaping.

“It’s hard to say right now whether it’s a net positive or negative,” Kennedy says.

Cohen and Kennedy are studying e-cigarette regulations from around the world. In countries with higher smoking rates, such as England and parts of Europe, it may make public health sense to promote e-cigarettes as a harm reduction alternative. Other parts of the world have a much lower rate of combustible cigarette smoking, so banning e-cigarettes may help maintain the status quo.

“You have to balance their usefulness in reducing harm to the individual smoker with proven stop-smoking methods and with the net impact on the population as a whole,” Cohen says. “This often puts us in a conundrum. It’s a very complex regulatory scene.”

The most popular new e-cigarette in the U.S. is Juul, about the size of a USB flash drive, which has the “sleek design of an Apple product,” Kennedy says. Young people like them not just for the sophisticated flavors like crème brulée, but also because they are small, easy to conceal and don’t look anything like a cigarette. They currently make up half of the U.S. e-cigarette market. Not to be pushed out by small startups, Big Tobacco has developed “heat-not-burn” products that heat tobacco below the temperature of combustion. Nicotine and other constituents of the tobacco leaves are aerosolized, providing the nicotine, taste and smell of cigarettes without the byproducts of combustion. Rule admits she knows even less about the safety of these latest iterations than about e-cigarettes, though she keeps two packs on her office shelf to remind her of the desperate need to play catch-up on their safety. 

FDA rules allow the agency to regulate e-cigarettes like other tobacco products, which means manufacturers must get approval before they promote their products as “a safer alternative to cigarettes.” But the FDA is facing a series of lawsuits from e-cigarette manufacturers and vape shops who argue that the rule violates the First Amendment by regulating non-tobacco vaping products like tobacco. So far, judges have ruled in favor of the FDA, but the issue is far from settled. To Rule, the answer is obvious.

“It’s better to sound the alarm before you poison millions of people,” she says.

The Institute for Global Tobacco Control is housed in the Department of Health, Behavior and Society.