Dr Farrah Kheradmand Explains the Mechanisms of Vaping Lung Injury

After 1 month we started seeing differences in the appearance of macrophages in mice that were exposed to electronic cigarettes, independent of nicotine, said Farrah Kheradmand, MD, a professor of medicine-pulmonary at Baylor College of Medicine and a staff physician at the Houston Veterans Affairs (VA) medical center. Kheradmand's research was presented at this year's American Thoracic Society (ATS) 2021 virtual conference.

Transcript

Can you give an overview of your talk "The Mechanisms of Injury from Vaping?"

We were very interested in the potential dangers of vaping with nicotine as an alternative to cigarette smoking. We did a very simple 2-by-2 experiment, because most of my patients at the VA wanted to know if vaping is safe, a safe alternative. That's how it's been advertised.

We took mice and we exposed them to vaping with or without nicotine, and cigarette or air. We wanted to compare what happens to inflammatory mediators in cigarette smoke compared to when you take nicotine in the form of aerosolized vaping. What we found was that they are completely different, meaning the inflammatory mediators that come to the lungs of mice when they're exposed to conventional cigarettes, is completely different than when you expose mice to electronic cigarettes.

Interestingly, when we exposed them for a chronic period of time, meaning that we didn't want to know what the immediate response was, we wanted to know what happens long-term, because most people are not just vaping for 1 or 2 days. They want to vape for a long period of time. Our experimental model was such that we could actually test that hypothesis. When we exposed mice to 4 months of cigarette smoke, we saw what we'd seen before. Mice get emphysema, they get inflammatory mediators, in particular, both innate and adaptive immune cells into the lungs.

What we found was that, while we didn't see emphysema in mice that were exposed to electronic cigarettes, the lung macrophages—these are innate immune cells in the lungs—looked markedly different than mice that were exposed to air or cigarette smoke. What is more interesting is that it didn't matter whether they were exposed to nicotine or not. This happened independent of nicotine. That's really how the story got started, that the change alteration of the innate immune cells in the lungs. That sets us on the path that we discovered.

Based on your research, what could happen to a person's lungs when they vape?

What we've found is that we exposed mice to electronic cigarettes and as early as maybe a month into it—and again, we've done a 4-month [exposure] which is almost like lifelong smoking in a human life, so 4 months of electronic cigarettes—as early as 1 month, we started seeing differences in the macrophages' appearance, again, independent of nicotine, in mice that were exposed to electronic cigarettes. When we identified the macrophages [they had] kind of a glistening look. When we stained them for oil, and within these vacuoles, we found that there are large amounts of oil that are deposited within the macrophages. That's why they appeared more translucent, they appeared that they had vacuoles in them.

Initially, we thought they were undergoing apoptosis, or cell death. But we looked at all the markers of it, and we didn't identify any such activity. But what we looked for and found is that there was an accumulation of lipids inside the cell body. When we cracked the cells open and did an unbiased approach to try to understand what these lipids are, what we found is that they're actually lipids that are normally found in surfactant. Surfactant is this lubricant that keeps the alveoli open, so that we can continue to keep our lungs open and breathe. What happens is these particular molecules called surfactant get recycled—a third of surfactant gets recycled every hour.

This is a very, very active process. Macrophages and alveolar type 2 cells, these are specialized cells inside the lung, they talk to each other, if you will. They actually coordinate recycling of surfactants such that we always have a fresh layer of surfactant in our lungs to keep the lungs open. Part of the macrophage function is to actually perform this recycling of surfactant. What we surmised is that the function of the alveolar macrophages is disrupted, such that in order for them to recycle the surfactant, they can't play a catch up. So they actually accumulate inside their cell body. That's why over time, it a cumulative thing.

While at about a month, we see a few macrophages that have this glistening and fat deposited, as the time progresses, at 3 or 4 months of exposure, we find almost the majority of the cells that have that phenotype. Meaning the more you get exposure, the more this process gets delayed, and the more macrophages become dysfunctional.