Sep 4, 2019 5:48 PM

Vaping May Hamper the Lungs' Ability to Fend off Infections

A study in mice finds that inhaling the vapor from an e-cigarette—no nicotine needed—raised their odds of dying after exposure to the flu virus.

A lot of otherwise healthy-seeming high schoolers and young adults are getting very sick. Since June, 28 cases of a mystery respiratory illness have been reported in Utah. Wisconsin has found 32 so far. Nationwide, more than 200 cases of patients with severe respiratory problems have been found in 25 states. One 30-year-old woman in Illinois died last month, and on Tuesday another death was reported in Oregon.

The patients, whose symptoms include difficulty breathing, chest pains, shortness of breath, and sometimes vomiting and diarrhea, have no known viral or bacterial infections. They just can’t seem to breathe normally. So far, the only known link between these previously healthy patients is that they had all recently vaped.

The Centers for Disease Control and Prevention, local state health agencies, and the Food and Drug Administration are scrambling for answers. With roughly 20 percent of high schoolers vaping, the question of what the practice does to the human body has taken on great urgency.

A study published today in the Journal of Clinical Investigation may add one piece to the puzzle. Researchers at Baylor showed that while mice exposed to e-cigarette vapor didn’t develop the same diseases as cigarette-smoking mice, they did develop another worrying set of problems.

The study found that inhaling just e-cigarette vapor, without any nicotine, fundamentally altered important cells that defend the mice’s lungs against infections. Farrah Kheradmand, a pulmonologist at Baylor who conducted the study, says those changes mean the lungs’ defenses against bacteria and viruses are “compromised,” leaving the mice with a dysfunctional lung immune system.

Immune problems have been connected to vaping anecdotally for years. But Ilona Jaspers, a professor at the University of North Carolina Chapel Hill, who was not involved in the Baylor study, says these findings are basically the first time that researchers are getting a look at how e-cigarettes alter lung function.

Lungs regulate the exchange of gases. Oxygen comes in, carbon dioxide goes out. But almost no one breathes in perfect, untainted air. Pollution, bacteria, and viruses can all hitch a ride. Lungs—and subsequently the rest of the body—are protected from these contaminants by a thin layer of lipids that coat the lungs and some very important cells called macrophages.

The lipid layer collects those invaders and toxins, binding to them and preventing them from reaching the air sacs. Macrophages, meanwhile, have two important jobs. First, they gobble up any invaders they encounter. They also recycle the lungs’ lipid lining, helping to renew that layer several times a day. As this mouse study shows, the solvents in vape cartridges appear to upset this crucial dynamic by damaging the lipids and sabotaging the macrophages’ cleanup work. Kheradmand isn’t exactly sure what’s happening to the lipids—they need more research to figure out what is changing—but whatever is happening is knocking the system out of whack.

Not only do the macrophages become less effective lipid recyclers, they also get diverted from their other task of screening out toxins and invaders. “Your immune system is out of balance,” says Jaspers, whose own work has found vaping causes similar immune problems in cells in the nose. “Because your system is not prepared, you’re getting sick.”

Some of the mystery cases the CDC is investigating have been diagnosed as lipoid pneumonia, a condition with similar symptoms to pneumonia but that isn’t caused by bacteria. Instead, lipoid pneumonia is an immune response in which fats build up in the lungs. In her lab, Kheradmand saw her mice develop such a condition without ever inhaling nicotine. “Just the chronic exposure to the solvents was enough,” she says.

It’s unlikely that vaping solvents alone can explain a nationwide spate of respiratory illnesses. “It’s not just going to be one component that we identify,” says Jaspers. THC could be exacerbating e-cigarettes’ harm, as could toxic flavorings, overly high nicotine concentrations, or vapes retrofitted to burn chemicals at dangerously high temperatures.

The study does help change how scientists think about vapers’ disease risks. Because most vape users are under age 25, they’ve only been vaping for a relatively short time. That means they may be suffering from a different set of ailments than lung cancer, emphysema, or other common afflictions among chronic cigarette smokers. “We shouldn’t be looking for the same diseases,” says Jaspers. “I think people are realizing that maybe we should go in there with an open mind.”

In fact, Kheradmand initially set out to look for a link between vaping and a common smokers’ disease, emphysema. At first she didn’t see an effect in her mice.

But then Matthew Madison, a graduate student in her lab, took a closer look at the cells in their control group, which had been exposed to the vape liquid without nicotine. That’s when they noticed the cells looked “strikingly different” from normal ones. So they refocused the study to examine how the solvents were altering the basic biology of the lungs.

Suddenly mice that seemed healthy could no longer protect themselves from small infections. When the researchers exposed them to small amounts of the flu virus—amounts that wouldn’t normally affect a mouse—the vaping mice died, unable to protect their lungs against even a small invading force.

The study does have its limitations. “Mice are not humans. They are not a perfect model,” says Laura Crotty Alexander, a pulmonologist at UC San Diego. Human lungs are much larger than mouse lungs, which might change how much vapor they absorb. And while the lung immune systems are similar, they aren’t identical. Mice have some different cells that could change how they respond to infection.

But mice have already proven themselves to be useful in lung research. Some of the initial work on tar and tobacco was conducted on mice and turned out to be relevant to humans as well. And mouse studies can produce insights at a speedy clip. “Exposing a mouse in this study for four months is sort of the equivalent of 25 to 35 years in a human,” Alexander says. “It’s our only tool to really tell us what the effects are in a mammalian system.”

In the meantime, the CDC urges people to stop vaping.