Loren Wold, PhD, Professor of Medicine and Nursing, and Associate Dean for Research Operations and Compliance in the College of Medicine at The Ohio State University, talks about the effects of vaping on teen boys’ hearts.
Interview conducted by Ivanhoe Broadcast News in April 2022.
Can you tell me what you and your colleagues are looking at in the lab in terms of vaping?
WOLD: When we initially started, we were looking at the impact of vaping and consumption of vaping products in adults. We’ve done that for many years and had not really seen much of an effect on the heart, so we decided to move into a space looking at adolescents and the effect of vaping and e-cigarette vapor exposure on adolescents. The reason we did this is because the majority of new users are adolescents. You traditionally don’t find adults who start using these products if they are not current/former cigarette smokers. Traditionally, they’ve used them to quit traditional smoking.
Adults are kind of switching over. Are they trying to use vapes as a way of getting off of nicotine?
WOLD: Yeah. So, there’s considerable literature showing that those who have smoked combustible cigarettes, who have a wish to quit and switched to solely e-cigarette products are able to quit. But that’s only in adults. We also, though, see a lot of people who are dual users. So, they’re using e-cigarettes because they’re not able to use traditional cigarettes in indoor places and places where smoking is not allowed.
When it comes to teen use, can you give me some context? Are there a lot of teens who are just vaping, who are doing both just from your study?
WOLD: We see dual use in adolescents and those that use both combustible cigarettes as well as e-cigarette products. Most new users are novel users, meaning they have not smoked any products before using e-cigarette products. This is the predominant user group right now.
How do you study this?
WOLD: We use an adolescent mouse model. It’s really difficult to do these sorts of studies in adolescent humans, partly because regulatory bodies will not allow the inclusion of this precious age group. So, we study mice that are three weeks old, which is equivalent to 12 to 15 years old. This age group is hard to study in any clinical studies. It requires parent approval and most institutional regulatory bodies will not approve these sorts of studies.
Can you walk me through how you did the research?
WOLD: We exposed male and female mice starting at weeks of age and we expose them until three months of age, when they are considered adult. This is considered a long-term process from adolescence to adulthood exposure. We expose them to vape products for several hours per day, five days per week. We give them the weekend off and start again.
What age would that correlate to in a human?
WOLD: I would say the three-month age group is around probably 20 to 30 years old. It’s hard because one day in a mouse age is equivalent to many more days in a human.
What did you find?
WOLD: When we exposed adolescent male mice, we found significant cardiovascular effects. The ability of the heart to pump and perform its regular circulatory assistive function was severely impaired. This was very reminiscent of a mouse with significant heart failure, for example. These effects were specific in males. Strikingly in females, we did not see these effects. We saw that there was protection from this dysfunction.
Why do you think that is? Are there any theories?
WOLD: What we found was that there was a significant increase in the enzyme that breaks down nicotine in the circulation. Once nicotine gets into the circulation, it’s broken down into multiple metabolites. This enzyme called CYP2A5 was significantly higher in females. So, the theory is that this enzyme being much higher was able to break the nicotine down much faster and therefore spare the effects of nicotine on the heart.
How confident are you and your team that this information correlates to humans?
WOLD: We know that in humans, females have a higher level of the enzyme CYP 2A6. It’s CYP2A5 in mice and CYP2A6 in humans. We know that females have a higher level before menopause, therefore it seems that females are potentially protected to a certain age.
What would a significant impact be like in a human?
WOLD: In our current studies, we have seen lung effects and a significant reduction in cardiac function. The ability of the heart to pump was severely impaired. This was very similar to mouse models we have for significant heart failure, for cardiomyopathies from long-term effects.
What do these findings suggest?
WOLD: What’s interesting is that this is one of the first studies to ever show that there are cardiac effects resulting of e-cigarette use in an adolescent population, and these had not been studied before because they’re really hard to study in adolescent humans. I think it points out that we need to study this precious population not only for the effects during adolescence, but to find out the long-term potential effects. These products have not been around for more than about 20 years so; we don’t know the long-term effects. We also don’t know the effects on future generations. Adolescents who likely will have children of their own, we don’t know if the effects on these adolescents could translate or could transfer into the next generation.
You mentioned that female mice seem to have that protective enzyme. You’re not suggesting that it’s OK for girls to smoke because they have this protective factor, right?
WOLD: Right. So, we looked at this at one snapshot in time and that’s one definite limitation. We also looked at one formulation of e-cigarette product. The problem with these products is that they’re not regulated, so we don’t know what the true constituents are. What we’re saying is, with our composition, which used a combination of multiple oils, which are traditionally used in the vapor products, there was this protection afforded to female mice. But we don’t truly know how this translates into the human population. The studies have not been done in this population. So, I think caution needs to be taken, not only in interpreting this as a protection, but, as I said, interpreting the potential that this could have on future generations. There is literature from exposure to air pollution, for example, which is simply particles in the air, that exposure prior to pregnancy can have an effect on future offspring. These are current studies that we’re doing right now.
How did you go about exposing the mice to the vaping?
WOLD: We use a translatable device, similar to what humans use, but it delivers a puff of smoke, or vapor, every minute. It is a model of chronic use. We do this for several hours per day, five days per week. We expose the whole animal. So, it’s an exposure of an animal in a non-stressed environment where the whole room that they’re in fills up with smoke and then is pulled back to dissipate the smoke.
How did you measure the impacts on the cardiovascular system?
WOLD: We use mechanisms exactly like you or I would have if we went to the cardiologist. We use echocardiography. We also insert a catheter into the ventricle and look at pressure development. So, the heart is a pumping device, and it needs to build up a certain pressure inside so that it can pump blood throughout the body. We look at the pressures that develop within the heart. Therefore, we use the same methods that would be used in clinics today.
What are the next steps in research?
WOLD: What we’re looking at now are the long-term effects. Do we see that these cardiac effects persist over time? We’re looking at the reversibility. If someone does use these products but then quits, will the heart function return to normal? We’re also looking more into the enzyme that I mentioned, CYP2A5, to see if we can artificially elevate this within the blood circulation in order to protect from nicotine’s effects on the heart as well as other organ systems.
Is there anything that you would want people to know about this body of research?
WOLD: I think caution needs to be taken in educating adolescents about the potential harms of these devices. The key is, we just don’t know. These are new devices. We don’t know the long-term effects, therefore it’s really important to stress the lack of information that’s out there on long-term effects. We’ve seen with air pollution that there can be effects with long-term exposure of air pollution, for example, on cognitive health. So, future issues with neurodegenerative disease, cardiac disease, respiratory disease are unknown.
END OF INTERVIEW
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