Exposing the Ill Effects of E-cigarettes

In early September this year, the Centers for Disease Control and Prevention reported six deaths among 450 patients in 33 states related to severe lung illness tied to e-cigarette use known as vaping. Two weeks later, two more deaths were added to that list. The severity and increasing incidence of the acute illness pointed to a cluster of pulmonary diseases related to e-cigarette use — one that demanded a thorough and quick investigation to alert the public. Serendipity may have played a hand at Johns Hopkins Children’s Center, where pediatric pulmonologists were already on the case.

"When e-cigarettes came out in 2010, there was a large schism between scientists and health care providers whether this was good or bad,” says pediatric pulmonologist Sharon McGrath-Morrow, who with pediatric pulmonologist Michael Collaco, among others, has been conducting and reviewing studies over the past five years on the effects of e-cigarette vapors on lung development. “One group said this is going to be a great way to get people off smoking combustible tobacco products, but as pediatricians, we were very concerned that these e-cigarettes being used by adolescents and children had never been tested.”

That motivated McGrath-Morrow, through animal studies, to look deeper into e-cigarette vapors produced by pod devices. She was among the first to find that, in neonatal mice, exposure to both nicotine and the chemical propylene glycol in e-cigarette vapor during the first two weeks of life adversely affected lung development. This is telling, she says, because human lung development continues until around age 18 (Histochem Cell Biol. 2018 Dec.; 150(6):677–691).

“They had fewer alveoli, a signal to us that this high-dose nicotine delivered by e-vapor was causing impaired alveoli growth,” says McGrath-Morrow, a member of the American Academy of Pediatrics Tobacco Consortium. “We know from other studies that tobacco smoke can do the same thing.”

In another study, McGrath-Morrow and others found that particles containing heavy metals and organic compounds in the vapors were smaller than those reported in traditional cigarette smoke (Inhal Toxicol. 2017 April; 29(5):197–205). The risk these ultrafine particles pose?

“These nanometer size particles can penetrate very deep into the lung and become systemic,” says McGrath-Morrow.

Fruit flavoring is another issue of investigation. While e-cigarette marketers have claimed the flavors are benign, when heated in an e-cigarette pod to vaporizing temperatures, researchers have found they may undergo thermal degradation and consequently produce potentially harmful compounds (Environ Sci Technol. 2017 Sept. 19; 51(18):10,806–10,813).

“These flavors were never intended to be heated up and inhaled deep into the lung,” says McGrath-Morrow. “The chemical composition actually changes.”

In her latest e-cigarette study, McGrath-Morrow and fellow pulmonologist Beth Laube studied mucociliary clearance, the lung’s primary innate defense mechanism. In young adult mice exposed to nicotine-containing vapors, they found that the lung clearance was slow compared to mice in the control group exposed to propylene glycol (Inhal Toxicol. 2017 April 29; (5):197–205).

“So we think nicotine is adversely affecting the cilia, which means you’re less likely to clear bacteria,” says McGrath-Morrow. “This is consistent with the overall idea that high nicotine levels adversely affect immune responses in the lung and may have an actual acute effect on inflammation.”

E-cigarette effects on brain development is yet another area of McGrath-Morrow’s research interests. Recognizing that studies have shown that children of mothers who smoked traditional cigarettes during pregnancy were at higher risk of attention deficit disorder, she exposed pregnant mice during their last stage of gestation to nicotine, propylene glycol or room air. The finding? Only the mice exposed to nicotine had outcomes associated with risk-taking behaviors as adults (PLOS One. 2015 Sept. 15; 10(9)).

“They were much more active, unable to concentrate, much more willing to go to the edge and less interested in protecting themselves from harm,” says McGrath-Morrow. “It was a proof of concept that early nicotine exposure through e-cigarettes could have an adverse effect on behavior in later life.”

Recognizing that the needs related to clarifying the risks of vaping were twofold — conducting research to determine its ill effects and raising awareness of those ill effects — McGrath-Morrow found pediatric pulmonologist colleague Christy Sadreameli, a volunteer media spokesperson for the American Lung Association, an ideal partner. Between treating young patients with respiratory disease at the Children’s Center, Sadreameli finds herself in front of the camera sharing the findings of McGrath-Morrow’s early research on television programs such as Good Morning America, on National Public Radio, and in various mainstream magazines and newspapers. The message?

“I think a lot of teens thought this is a cool new device that has no health effects, but we’re seeing real cases that they need to know about,” says Sadreameli. “Then I think they will start to take this seriously.”

Sadreameli advocates for pediatricians to screen adolescents for e-cigarette use, and the federal government and state governments to regulate pod-based products. Nicotine, a well-known toxin, is highly addictive. One e-cigarette pod can contain up to 52 milligrams of nicotine, the equivalent of nicotine in 20 cigarettes. Online sales and flavorings marketed to attract younger children are other concerns.

“Flavored e-cigarettes are one of the main reasons teens use these devices,” says Sadreameli. “If all flavors were banned, that would decrease uptake among young people. That’s one step the FDA could take.”

Regulatory agencies and states appear to be heeding the message. The Food and Drug Administration recently issued a warning letter to JUUL Labs, the largest e-cigarette company, that it illegally marketed its vaping products as less harmful alternatives to traditional cigarettes. Michigan recently became the first state to ban fruit flavored e-cigarettes.

McGrath-Morrow and Sadreameli are optimistic that e-cigarettes will be appropriately regulated, but they do not plan to abandon their bench work and advocacy anytime soon.

“It took us 30 to 40 years to understand the full extent of tobacco’s impact on the lung,” says McGrath-Morrow. “We have this unique opportunity now to intervene earlier, to warn people that this could potentially be a real problem over time.”