A new study by researchers at the Yale School of Medicine describes the mechanism by which vaping e-cigarettes can hurt the body’s ability to combat viruses.

The study states that cells in the airway cannot effectively combat both viruses and damage from inhaled irritants. Headed by Ellen Foxman, a laboratory medicine professor at the medical school, the Yale research team found that there is a trade-off between defense against oxidative stress, which is chemical damage in the lungs that is a precursor of lung cancer, and defense against rhinoviruses, the most frequent cause of the common cold and asthma attacks. The study was published in the journal Cell Reports on Sept. 11.

“Ways of detecting viruses have gotten much better in the past decade or so,” Foxman said. “[Researchers] have found that these viruses enter our nasal passages a lot more often than we actually get sick. What that means is that our body’s actually pretty good at blocking these viruses. So what we want to do is figure out how that works because if we could make that happen more often, we could reduce a lot of illnesses.”

Rhinovirus grows in epithelial cells, which form the lining of the airway from the nose to the lungs. The virus enters the cells and makes copies of itself, causing an infection, but epithelial cells can block the virus from spreading. Although scientists have a sense of how this process works at the molecular level, in this study, the researchers investigated how these defense pathways are activated, Foxman said.

Researchers compared epithelial cells from the nose to those from the lungs. Under the same conditions, they found that antiviral response was stronger in nasal cells.

But on the other hand, the cells from the lungs displayed more activity in a different defense pathway: protection against oxidative stress, which is damage caused by pollution, cigarette smoke, pollen, irritating chemicals or high oxygen levels.

When the team applied a low level of cigarette smoke to the cells, they were able to adapt and survive the smoke, but their ability to fight viral infections became weaker. When the cells’ defense pathway against oxidative stress was eliminated, however, they were not able to adapt or survive at all.

Researchers concluded that cells can adapt to survive oxidative stress but at the cost of lowering their antiviral defense.

“Factors that stimulate antioxidant pathways, such as exposure to cigarette smoke or vaping e-cigarettes, would interfere with your body’s ability to defend against respiratory viral infections including the common cold,” said Akiko Iwasaki, a professor of molecular, cellular and developmental biology at the School of Medicine and a co-investigator of the study.

Prior to this study, researchers already knew that smokers were more vulnerable to serious infections from rhinovirus, Foxman said. She noted, however, that the mechanism behind that phenomena — explained by the trade-off between defense against oxidative stress and against rhinovirus — was not known before this study.

According to Iwasaki, the lungs are constantly exposed to environmental pollutants and microbes. Because defense against oxidative stress seems to be the priority of the lungs, it is important that the air passages of the lungs are open to conduct as much air as possible even in the face of viral infection.

As a trade-off, antiviral reactions, which can cause inflammatory changes to block the airway, are kept low, Iwasaki said.

Stephen Stearns, a professor of ecology and evolutionary biology who was not involved in the study, agreed, saying that a single cell cannot be good at fighting both oxidative stress and viruses. Therefore, he said, the cell deploys the virus-fighting capacity in the nose, where the viruses arrive, and the oxidative stress-fighting capacity in the lungs, where the threat of lung cancer is more significant.

“The idea of trade-offs has been around for a long time, but this is the first time I have seen it deployed so tellingly in this context,” Stearns said. “[The research] appears to be telling us something deep and general about how and why cells specialize the way they do. In this case, the insights are into both defense against infectious disease and defense against cancer. That those two functions might trade off has not previously been as appreciated as it should now be.”

The Foxman Lab is new to Yale and is currently recruiting students at all levels.

Eui Young Kim | euiyoung.kim@yale.edu .

Yale College Class of 2021; Yale Law School Class of 2025