By Veronique de Turenne. E-cigarettes originally were intended as a replacement for carcinogenic tobacco products, but today it is known that they foster addiction and create their own sometimes life-threatening medical issues.
Even before the patient crashed, her lungs unable to function, critical-care pulmonologist Kathryn Melamed, MD ’12 (FEL ’18), sensed that something about the case was amiss. The patient was young, just 18 years old, and prior to her hospital admission, she had been healthy. Yet, here she was, in the ICU at Ronald Reagan UCLA Medical Center, with a high fever, shortness of breath and a wet, heavy cough — winter-flulike symptoms, even though it was mid-August.
The illness that brought her to the hospital progressed so rapidly, the entire care team was startled. Soon after becoming Dr. Melamed’s patient in the ICU, the young woman struggled to breathe. Unlike an initial X-ray, in which a white haze at the bottom of her lungs suggested pneumonia, a subsequent scan ordered by Dr. Melamed came back almost completely opaque. The patient’s lungs, severely inflamed, had rapidly filled with fluid.
“You might expect someone who is chronically ill or who has a weakened immune system to develop a pneumonia that gets quite severe,” Dr. Melamed says. “But to see someone who is healthy and young develop a severe illness that quickly is very concerning, and it quickly becomes life-threatening. There was a real chance that she was going to die.”
After almost a week on a respirator under sedation, the patient did begin to recover. At the same time, the Centers for Disease Control and Prevention (CDC) released a warning about a spate of unusual vape-related lung injuries, which corroborated Dr. Melamed’s suspicions.
“This all took place just before the CDC gave its warning, but there had been a few news stories about potential vape-related cases in Ohio, so I had an idea of what might be going on,” Dr. Melamed says. “Then, with the CDC’s announcement, we got even more confirmation that this was what was happening with our patient.”
Severe lung injuries have come to symbolize America’s growing vaping crisis. Known as EVALI, an acronym that stands for ‘e-cigarette or vaping product use-associated lung injury,’ it was officially recognized by the CDC in August 2019. EVALI cases have led to numerous long-term hospitalizations, several lung transplants and a number of deaths. As of late February, the agency reported more than 2,807 hospitalized EVALI cases in all 50 states and 67 deaths. Initial research has linked the EVALI outbreak to black-market cannabis-based products and certain additives, but the exact cause still is not known.
The dramatic and grave illnesses of the EVALI epidemic have dominated news coverage of vaping. But physicians at UCLA warn that nicotine-based e-cigarettes, which now are addicting children and adolescents in record numbers, pose a far greater danger. Offered in an array of enticing flavors and loaded with amped-up forms of nicotine, e-cigarette technology opened a Pandora’s box of ills. And, with lax oversight compounded by a lack of regulation, most of the product’s ingredients remain a mystery.
So do the potential effects of both short- and long-term use. Without crucial information, health professionals say that young people have become test subjects in what amounts to a vast and unregulated experiment. At the same time, with billions of dollars in annual profits at stake, competing interests are fighting for control of the products, the laws that govern them and the narrative.
“We have been presented with a very serious problem related to lung injury, largely with those products that deliver THC; however, the true catastrophe lies in the addiction of young people and children to nicotine, and we should not take our focus off that problem at any time,” says lung-cancer investigator Steven M. Dubinett, MD (RES ’84), associate vice chancellor for research and division chief of pulmonary and critical-care medicine. “The forces at play are so powerful, that we need to be able to place research and facts in front of our community, our patients and the world about this very serious problem.” Otherwise, he says, “the enormous harm that is in the offing for children and young adults amounts to a tsunami of addiction that is swelling to engulf an entire generation.”
E-CIGARETTES, ALSO KNOWN AS ELECTRONIC NICOTINE-DELIVERY SYSTEMS, or ENDS, were invented with the initial intent of helping smokers quit. Today’s devices, which bear little resemblance to the original mechanism, go by a variety of different names. These include vapes, vape pens, tanks and mods, nomenclature that refers to the various technologies involved in nicotine delivery. They work by using a battery to heat a liquid solution until it produces an aerosol that can be inhaled. The solutions, often referred to as e-liquids, typically include nicotine and flavoring agents, as well as solvents, which help generate the aerosol.
Users purchase a vaping device, which they then fill with the e-liquid of their choice. There are thousands of products on the market offered by major manufacturers as well as mom-and-pop operations. The devices also are the subject of a thriving black market, with a variety of off-label products available online. To make their own products, users have only to turn to YouTube to find tutorials on making e-liquids.
In the commercial vape marketplace, both the e-liquids and the devices that deliver them have, until recently, been largely free from regulatory oversight. In addition to two basic ingredients — nicotine and solvents — the e-liquids include numerous unnamed ingredients. “These are unregulated products, so really we don’t know what’s in them,” Dr. Dubinett says.
The content of the e-liquids varies not only from manufacturer to manufacturer, but also from batch to batch. This makes it impossible for users to know what’s in any of the thousands of different products that are available and poses unique challenges to researchers working to study the health effects of vaping habits.
“Unlike nicotine-replacement therapies like gum or a patch, which had to undergo product review, with vaping we are talking about unregulated products that are being marketed directly to the consumer. That makes it really difficult to comment on the safety of these devices,” says Michael K. Ong, MD, PhD, UCLA professor-in residence of medicine and health policy and management and chair of the California Tobacco Education and Research Oversight Committee.
“The way a regular cigarette is constructed is very well-known, whereas these vaping products haven’t undergone the rigorous testing of other consumer products.” That, Dr. Ong says, is a critical concern. “This is a technology that lets a manufacturer add all sorts of additives and flavors, but we have not had a regulatory environment that restricts them in any way, let alone one that requires manufacturers even to reveal what’s in their products.”
What is clear is how strongly nicotine-based e-cigarettes appeal to — and, ultimately, addict — the youth market. According to the CDC, most tobacco smokers launch their habits in early adolescence. Research shows that close to 90 percent of smokers will have tried their first cigarette by the age of 18. Only two percent of smokers will start the habit after age 26. Thanks to decades of education, regulation and advocacy, the youth smoking rate had hit a historical low at the turn of the last century.
Then came vape products. Peddled in appealing flavors like mango, fruit, bubblegum and crème and presented in cheery, child-friendly packaging, they took direct aim at the youth market. The result was a spike in the numbers of new e-cigarette users and an equally dramatic drop in their age. Between 2011 and 2015, the use of e-cigarettes among high school students surged 900 percent, according to a report released in 2016 by then-Surgeon General Vivek Murthy. Between 2018 and 2019, the number of middle and high school students who used e-cigarettes jumped by 1.8 million, from 3.6 to 5.4 million. By 2019, more than 10 percent of middle school children reported vaping in the previous 30 days. This number jumped to 27.5 percent when high school students were surveyed.
The biggest driver of the e-cigarette revolution has been Juul, a company whose name quickly became a verb to describe the use of its products. The company made savvy design decisions for its vaping devices, which resemble a flash drive and can be charged in a USB port. They also released products that critics say deliberately targeted the youth market, including children, with cute names in kid-friendly flavors and bright-colored cartoon-like packaging.
“Juul often is referred to as the iPod of e-cigarettes,” says Eric Hamberger, MD, a pediatric pulmonologist at UCLA. “They use a lot of the same design elements that you see in Apple products, like the small, brushed-metal cases that are sleek and squared-off. But Juul’s real claim to fame is the formulation that they came up with — nicotine salts.”
Based on research conducted by legacy tobacco companies in the mid-1900s, Juul adjusted the chemical formulation of its e-liquids. Known as nicotine salts, they make the stimulant easier to use and markedly more palatable. “The engineers at Juul realized that a lot of the harshness of nicotine came from the pH of the liquid,” Dr. Hamberger says. “When people took a hit of the e-cigarette vapor at a lower pH, which allows it to be stable in the liquid form, it’s much less harsh on the inhale. With nicotine salts, they really turned vaping into a science.”
Gone was the choking, burning sensation that beginning cigarette smokers endure as they inhale. Instead, with solvents and other additives to “soften” the aerosol and a range of flavors to appeal to the palate, the company created a product that even first-time smokers could take deep into their lungs from the first pull. The company soon began to offer products with dramatically higher concentrations of nicotine. Previously, vendors sold e-liquids with nicotine concentrations in the one-to-three-percent range. But Juul raised the ante with refill products that deliver five percent nicotine. Between 2016 and 2017, sales at Juul jumped 641 percent. By December 2017, the company’s products made up the biggest share of the vaping market. That spike in nicotine concentrations sent competitors scrambling to catch up. Today, refills at five-to-sevenpercent nicotine are the industry standard. As a consequence, widespread addiction has followed.
HIGH CONCENTRATIONS OF NICOTINE ARE PARTICULARLY HARD ON ADOLESCENTS, who are much more likely to become addicted due to their developing brains, says Bonnie Halpern- Felsher, PhD, a developmental psychologist and professor of pediatrics in the Division of Adolescent Medicine at Stanford University with expertise in health-related decision-making by adolescents and young adults. This propensity to addiction during adolescence is due to brain development that takes place during this period. “As you grow into adulthood, your brain continues developing and looking for cues about synaptic connections that it can prune away and those it needs to keep,” Dr. Halpern-Felsher says. “When you introduce a substance during this time, the brain pathways associated with the drug use are kept and strengthened. In the case of e-cigarettes, the nicotine-receptor pathways become more strongly connected with the brain’s internal pleasure pathway, the dopaminergic reward system, making it much easier for young people to become addicted to nicotine and also more difficult to quit that addiction.”
With little understanding of what vape products contain, adolescents have been ideal targets for the vaping industry, she says. “They’ve been lied to by the e-cigarette industry, which went around saying these products are healthier, safer than cigarettes and are meant for smoking cessation,” she says. “But then they also advertised the products as being fun and invited young people to just give them a try. It becomes clear when you look at the ads, which directly target children and adolescents with the flavors and the names.”
That leap from merely fooling around with vape products to being unable to put them down turns out to be all too easy. “Nicotine is one of the most addictive compounds there is, so much so that it has been compared to heroin,” says UCLA cardiologist Holly R. Middlekauff, MD (RES ’89, ’92, FEL ’90, ’92). “And then it’s just tremendously hard to break that addiction, which is part of why smoking cessation rates, despite everybody knowing how bad it is for you, are so low, in the range of five or 10 percent.”
The original argument in favor of e-cigarettes focused on their use in place of tobacco products containing scores of potential carcinogens such as arsenic, ammonia, hydrogen cyanide and benzene. Nicotine, while addictive, was believed to be harmless. But emerging research is revealing some inconvenient truths about e-cigarettes and the nicotine they deliver. Not only is there evidence that the solvents and other chemicals in e-liquids may play a role in cardiac and pulmonary disease, but also nicotine itself is emerging as a health hazard.
In her research, in collaboration with UCLA infectious-diseases specialist Theodoros Kelesidis, MD (FEL ’11), Dr. Middlekauff has detected a link between the use of e-cigarettes and oxidative stress, a harmful process that adversely affects numerous cellular structures, including proteins, lipids, membranes and DNA. “We have an abstract that we are presenting at an American College of Cardiology meeting that shows chronic electronic-cigarette users exhibit increased levels of oxidative stress as compared to non-users,” she says. “Our data show that these products are causing real changes in immune cells, which is disturbing because not only does oxidative stress increase the risk for cardiovascular disease, it also has been implicated in cancer, lung disease and premature aging.”
The results reinforce the pressing need for transparency in e-cigarette ingredients, Dr. Middlekauff says. “You get young people who really don’t know what’s in the products they’re using — some of them don’t even know if there’s nicotine or not — and they become addicted very quickly. This is setting them up for lifelong exposure to oxidative stress and inflammation, which is going to get them later,” she says. At the University of North Carolina (UNC) School of Medicine, researchers also have identified troubling changes in the lungs of vapers. Robert Tarran, PhD, professor of cell biology and physiology and a member of UNC’s Marsico Lung Institute, says these changes are similar to those seen in cigarette smokers. These include elevated levels of proteases, a kind of molecular scissors that cut up other proteins. The link between high protease levels and lung diseases, such as emphysema and COPD, is well-established.
“We found that just the nicotine alone causes the immune cells to release proteases, so clearly there’s a potential for lung disease,” Dr. Tarran says. “And now, vaping is attracting a whole new generation who would never have smoked otherwise.”
Trying to persuade users that their products of choice may, in the long run, not be much better than cigarettes is an uphill battle, Dr. Tarran says. “I’ve had vapers say that they’ve been using these products for 10 years without any major effects, so that must mean that vaping is safe. But that’s a false argument,” he says. “Even with tobacco smoking, if you start smoking when you are 20, you’re still pretty healthy by the time you get to 30. It’s not until a few decades later, about retirement age, that it gets you.”
OVERSIGHT OF THE E-CIGARETTE INDUSTRY IS GEARING UP ON MANY FRONTS. But a growing number of health care professionals say it’s too little too late. A patchwork of state regulations have banned flavored vape liquids and raised the legal age for purchasing vape products. Federal enforcement of restrictions on flavored e-cigarettes kicked in in February. Thanks to a U.S. District Court ruling last summer, manufacturers had until May 2020 to submit their products to the Food and Drug Administration for public-health review. But the flavor ban focuses solely on reusable vape products, such as Juul, which creates some big loopholes. Many in the youth market have already moved on to disposable devices, which continue to sell flavored products with impunity.
Meanwhile, with billions of dollars in profits at stake, Big Tobacco has been buying into the e-cigarette industry. Last year, Altria Group, Inc., the maker of Marlboro cigarettes, purchased a 35 percent stake in Juul for $12.8 billion. It has joined other tobacco advocates in lobbying lawmakers, often successfully, to loosen, weaken or postpone proposed e-cigarette regulations. At the same time, Juul has pursued a number of prominent physicians and scientists to become its chief medical officer.
The task of helping kids quit vape products often falls to pediatricians like Dr. Hamberger. It can be a heavy lift. “You can talk with them about the science or the health effects that they will face in the future, but that’s really not going to get you anywhere,” he says. “I’ve found that the most convincing thing I can tell an adolescent is how this habit is going to affect them today, right now.”
Behavioral symptoms, such as sleep disruption, depression, ADHD and poor mood, catch their attention. “When you start getting into the psychological effects of using these products, it tends to scare them,” Dr. Hamberger says. “If you tell a teenager that he or she is not going to feel well emotionally, they tend to listen more.” With young athletes, who are invested in physical performance, the arguments can be a bit easier to make. “I’ll talk about symptoms like coughing and immune function and shortness of breath, and they kind of raise their eyebrows, and I know that they’re listening,” Dr. Hamberger says. “But, in the end, you’re still talking about the future, about long-term consequences, and that just doesn’t have much of an effect on them at that age.”
All of which comes full circle, back to Simah Herman, the young woman struggling to breathe in the ICU at UCLA. Her path to addiction, her unfettered access to products and her lack of understanding about the potentially grave consequences of vaping exemplify the challenges so many adolescents face.
It was while she was unconscious and on a ventilator that a friend shocked Herman’s mother with the news that her daughter had been secretly vaping since she was 15 years old. She had been able to hide her habit because the vape tech is so small, so easy to use and leaves no telltale odor. Herman began with a random puff or two from friends’ vape devices at school. Then, feeling bad about always borrowing, she began buying her own vapes. Despite her age, she was able to purchase cartridges at smoke shops by claiming to be 22. No one questioned her or checked her ID. Soon, Herman was using a vape cartridge per day, the equivalent of a pack of cigarettes. She also began vaping cannabis, some of it black-market products. After searching her daughter’s room, Herman’s mother returned with a backpack filled with an assortment of vape products.
Later, conscious but still on the ventilator, Herman wrote a sign that she held up to the camera, and then she posted the photo to her Instagram account. “I want to start a no vaping campaign,” it said. While recovering from her ordeal, she shared her story with reporters. “I didn’t think of myself as a smoker. Like, it’s just a different kind of smoke,” Herman told ABC News. “The vaping just makes it seem like nothing. Like you’re doing nothing wrong.”
Then, later, despite her medical ordeal, she admitted how much she still misses vaping. “That’s been the hardest thing,” Herman said. “Staying away from it.”
Veronique de Turenne is a freelance writer in Los Angeles.