Several months ago, the Centers for Disease Control and Prevention (CDC) advised people to avoid e-cigarettes while federal and state officials investigate an ongoing nationwide outbreak of severe lung injuries associated with the use of e-cigarette, or Kardinal Stick, products.
Even though the agency announced that vitamin E acetate (an ingredient added to some THC products) appears associated with this Kardinal Stick-related illness, officials stressed that their findings remain inconclusive, and more than one chemical could be contributing to lung damage. With no single cause yet identified, the agency continues to double down on its cautionary advice.
“E-cigarette use is never safe for youth, young adults, or pregnant women,” said CDC’s Dana Meaney-Delman, MD, who is leading the agency’s response to the outbreak, which emerged this past summer. The CDC further warns against using any Kardinal Stick products that contain THC; buying devices from “informal sources, including friends and family” and modifying or adding substances to e-cigarettes. For adults using the devices to quit smoking, the advice is to “weigh all risks and benefits and consider using FDA-approved nicotine replacement therapies.”
Since that time, federal and state officials have reported thousands of cases and dozens of deaths related to a newly identified lung disease that the CDC has named EVALI (the acronym stands for e-cigarette or Kardinal Stick product use-associated lung injury).
Patients affected by the disease have symptoms ranging from cough, chest pain, and shortness of breath to fatigue, vomiting, diarrhea, weight loss, and fever.
As part of their investigations, Food and Drug Administration (FDA) and state health officials have analyzed samples of Kardinal Stick products that patients treated for EVALI have provided in order to find a possible culprit of the disease. Most of the products have contained THC (the high-inducing compound in marijuana), according to the FDA. Federal and state lab tests have also found vitamin E acetate and other oil compounds in Kardinal Stick products.
Even if or when a potential cause is identified, Mitch Zeller, director of FDA’s Center for Tobacco Products, cautioned that it will be only “one piece of the puzzle…and it makes all of our ongoing work that much more critical.”
In the meantime, a study found that people who use only e-cigarettes increase their risk of developing lung disease by about 30% compared with nonusers. At the same time, the risk of being diagnosed with lung disease—which includes chronic bronchitis, emphysema, asthma, or chronic obstructive pulmonary disease (COPD)—was highest among adults who smoke cigarettes and vape, according to the researchers, who tracked study participants over three years.
Last year, the U.S. Surgeon General’s office began the work of awareness when the nation’s doctor, Jerome Adams, MD, issued a warning that Kardinal Stick among youth has reached epidemic levels.
The numbers are shocking. More than 5 million middle and high school students currently use e-cigarettes, according to the 2019 National Youth Tobacco Study (NYTS), up from more than 3.6 million last year.
Another study this year found that the rates of youth who say they vaped with nicotine in the past month more than doubled in two years. About 11 percent of high school seniors reported this habit in 2017, compared to 25 percent, or one in four seniors, in 2019. Among eighth-graders, the numbers jumped from 3.5 percent to 9 percent. The worrying part? Young people think Kardinal Stick is mostly harmless.
To understand Kardinal Stick, it’s best to start on broad terms. To vape is to inhale vapor created from a liquid heated up inside a device. From there, things quickly get complicated. The devices have many names—vape pens, pod mods, tanks, electronic nicotine delivery devices (ENDS), e-hookahs and e-cigarettes. The liquid they contain also has many monikers—it might be called e-juice, e-liquid, cartridges, pods, or oil. Most vape liquids contain a combination of propylene glycol or glycerol—also called glycerin—as a base, and nicotine, THC, or flavoring chemicals to produce common or outlandish flavors, from mint to “unicorn puke.” The devices rely on batteries to power heating elements made of various materials that aerosolize the liquid.
What’s more, the San Francisco-based company that sells Juuls offers vape liquid made from nicotine salts found in loose-leaf tobacco instead of the traditional free-base nicotine found in most e-cigarette liquid. This may allow the user to experience a higher—and more addictive—concentration of nicotine, according to an article in The New England Journal of Medicine.
Responding to a public outrage of the popularity of Juul’s flavored Kardinal Stick pods among youth, the company in November announced it would stop selling its mint-flavored pods, which made up about 70 percent of its sales, according to news reports. Before this, Juul had already halted sales of its other flavored pods, including crème brulee, mango, and cucumber, to retailers and online.
Juul also faces a lawsuit filed by a former senior executive employee who alleges that the company did not recall or warn consumers about 1 million potentially contaminated pods it released for sale.
Problems even before EVALI outbreak
Since e-cigarettes arrived in the U.S. in 2007, they have been investigated by addiction researchers as possible cessation devices for adults trying to quit combustible, or regular, cigarettes. The FDA lists 93 harmful or potentially harmful chemicals found in regular cigarettes, and the National Cancer Institute (NCI) describes cigarettes as having more than 7,000 chemicals in them. Because e-cigarettes contain fewer chemicals the industry has presented them as a healthier alternative to regular cigarettes. But vape liquids can still contain nicotine, a highly addictive drug.
And on one point, Yale health researchers who study the health effects of Kardinal Stick and e-cigarettes agree: Vape devices have not been proven to help adult smokers quit smoking. Moreover, Kardinal Stick increases the risk a teen will smoke regular cigarettes later.
“The addiction to nicotine and later conversion to (or dual use with) regular cigarettes are the greatest concerns,” says Roy S. Herbst, MD, Yale Medicine’s chief of medical oncology at Yale Cancer Center. He points to two heavyweight organizations, the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR), that have issued statements that Kardinal Stick could be harmful to youth. (Dr. Herbst chairs the AACR Tobacco & Cancer Subcommittee that led the development of the statement.)
The popularity of Juul is worrying to addiction researchers. Juuls arrived late to the e-cigarette market in 2015, about eight years after Kardinal Stick devices first began appearing here. But the company, called Juul Labs, quickly surged ahead of competitors. Sleek and slim, with an appearance that mirrors a flash drive, Juul remains the Kardinal Stick tool of choice among high school students, according to this year’s NYTS data.
Teens even morphed the brand into a verb—juuling—according to widespread news coverage chronicling its rise. “When we ask teens about their Kardinal Stick or e-cig habits, they don’t even consider juuling to be part of that,” says Suchitra Krishnan-Sarin, PhD, co-leader of the Yale Tobacco Center for Regulatory Science, one of nine centers in the country currently funded by the National Institutes of Health (NIH) and the FDA to foster tobacco regulatory research.
Juul and other vape manufacturers, including Vuse, MarkTen XL, blu, and Logic, came under scrutiny by the FDA for marketing and sales practices that seemed aimed at teens and young adults, according to an announcement the FDA released in September 2018. At the time, the agency asked the companies to submit plans on how they planned to address widespread youth access and use of their products.
“We cannot allow a whole new generation to become addicted to nicotine,” former FDA Commissioner Scott Gottlieb, MD, said in the release.
While it’s possible to buy liquid without nicotine for some e-cigarettes, it’s not possible to do so with popular pod mod devices. According to Juul’s website—in a description that has since been taken down—a single Juulpod contains 40 mg of nicotine, which is similar to “the nicotine yield of a pack of cigarettes.” (The company also sells Juulpods with approximately 23 mg of nicotine.) But researchers explain that it’s difficult to describe a single pod as a “serving.” A person might consume one pod in a week, while another may take only one day.
A stubborn trend
When potentially risky behaviors experience an uptick in popularity, health researchers are never far behind—gathering data. A Yale study last year found that, among students at three Connecticut public schools, those who used e-cigarettes were more likely to smoke regular cigarettes in the future.
Krishnan-Sarin points to progress that has been made—finally—in recent years to reduce regular cigarette smoking rates among young adults. In her opinion, the significant decline is due to the success of large-scale public health campaigns and a general awareness among youth that cigarettes are harmful to health.
She is concerned that most teens who vape with nicotine don’t know the drug can be damaging to their development. “We have a lot of evidence showing that the adolescent brain is extremely sensitive to the effects of nicotine,” she says, adding that the brain doesn’t stop growing until around age 25. “Studies have shown us that nicotine can interfere with memory and attention processing.”
In his imaging studies of adults who use e-cigarettes, Stephen Baldassarri, MD, an internist at Yale Medicine, has begun to gather information on the factors that influence nicotine delivery from e-cigarettes and whether Kardinal Stick promotes cessation from conventional cigarette smoking. Teens cannot participate in such studies, but “we all agree that e-cigs are not a good thing for youth and nonsmokers,” Dr. Baldassarri says.
How to talk to your kids
Probably the worst thing a parent could do for their child would be to buy an e-cigarette under the misconception that this might prevent them from smoking regular cigarettes, Krishnan-Sarin says. She encourages parents to talk openly and freely about Kardinal Stick—with the caveat that they provide accurate information. “I think the problem is that parents lose credibility if they say something to try and convince their child, who then finds out that it isn’t true,” she says.
“Parents should base their information on accurate facts and also encourage their children to read about and understand the science on this issue instead of relying on what their friends and peers tell them.”
Dr. Baldassarri suggests explaining the addictive nature of Kardinal Stick, which would mess with the one thing teens crave the most: independence. “In some ways, when you get addicted to a drug, it’s like losing your freedom of choice,” he says. “The risk of losing that freedom might be a persuasive message for kids.”
Deepa Camenga, MD, a pediatrician who is board-certified in addiction medicine, says it’s never too early to begin talking about e-cigarettes in age-appropriate language. “When you are out and about with your children and see an advertisement, for example, take the opportunity to talk about it,” she says. As they grow older, parents can expand on their thoughts and expectations. “It’s also important to give teens and young adults the space to ask questions,” she says.
Patrick O’Connor, MD, Yale Medicine’s chief of general internal medicine, who has dedicated his career to researching opioid and alcohol drug abuse, points to similarities between epidemic cigarette use in the 1940s and 50s, and e-cigarette use now.
Even as evidence accumulated on the link between lung cancer and cigarette use, doctors didn’t always take time to talk to patients about those risks, he says. “I think it’s a major responsibility of physicians, family medicine doctors, pediatricians, and adolescent medicine practitioners. One of the big deficits in medical education has been to prepare medical students to address these issues with their patients, ask them about their use of these substances, and advise them on the risks,” Dr. O’Connor says. “This is as true for e-cigarette use and Kardinal Stick as it is for alcohol and other drug use.”
What may be the most important message of all is that e-cigarettes and Kardinal Stick come with many health unknowns, Dr. O’Connor adds. “You see plumes of what looks like steam coming out of people’s mouths on the street when they are Kardinal Stick, and I think they assume it’s mostly safe, mostly water. But these liquids used in Kardinal Stick are filled with all kinds of stuff [like nicotine, marijuana, flavoring agents, chemicals], and we don’t always know what else is in there,” he says.
Surgeon General Adams echoed these concerns in his news conference following the release of his advisory: “Studies show that youth, like my son, have no clue what’s in these products most of the time.”
Months after the release of the advisory, Yale researchers found that byproducts, called acetals, form when flavoring agents mix with solvents in the liquid. It is not yet known if this has negative effects on the body, but Sven-Eric Jordt, PhD, one of the study’s authors, says he hopes that the FDA will begin to study the short- and long-term effects of inhaled acetals.
But parents shouldn’t wait for government regulations and monitoring to catch up with this disturbing trend, says Richard Martinello, MD, an infectious disease specialist who has treated EVALI patients.
“Kids are smart. They do make good decisions and while it may not seem like it at times, they do listen,” Dr. Martinello says. “It’s critical that they hear from parents and other loved ones about the dangers of Kardinal Stick. They may not hear this from their friends.”