Fourth-generation vaporization devices display a mix of cellular biomarkers indicative of immune suppression

Not all electronic cigarette devices are created equal. Some fourth-generation models — such as Juul devices — are associated with unique changes in markers of immune responses in our airways, according to a new peer-reviewed paper by UNC School of Medicine researchers led by toxicologist Ilona Jaspers, PhD, director of the UNC Center for Environmental Medicine, Asthma and Pulmonary Biology and Director of the UNC Curriculum in Toxicology and Environmental Medicine.

Lead author Elise Hickman, PhD, a recent graduate of Jaspers’ lab, and colleagues, who published their research in the American Journal of Respiratory and Critical Care Medicinefound that users of fourth-generation nicotine salt-containing devices display a unique blend of cellular biomarkers indicative of immune suppression.

Our work demonstrates the importance of considering device type in future clinical, epidemiological and mechanistic studies of the health effects of e-cigarettes. We also think this research could help regulators determine which products cause the most severe types of biological changes in airway cells that are important for maintaining good health.

Ilona Jaspers, professor of pediatrics and microbiology and immunology, University of North Carolina Health Care

Electronic cigarettes have become increasingly popular over the past decade. Some people started using them as a smoking cessation tool, thinking that vaping was a safer alternative, both in the short and long term. Because electronic cigarettes contain no tar, consumers assumed that vaping reduced their risk of cancer down the road.

“It is impossible to know whether vaping reduces the risk of cancer or many other long-term conditions,” Jaspers said. “It took 60 years of research to show that smoking causes cancer.” E-cigarettes have been around for about 15 years. “Yet research from our lab and many others has shown many of the same acute respiratory biological effects that we have documented in smokers,” she said. “And we’ve seen some changes in cells and immune defenses in people who vape that, frankly, we’ve never seen that before, which is very concerning.”

Most worrying for researchers, doctors and public health officials is the fact that teens who otherwise wouldn’t have tried cigarettes have started using e-cigarettes, which contain nicotine — a drug with its own health effects, even beyond addiction — and thousands of chemicals. , many of which the FDA has approved for eating but not inhalation.

Several studies have shown that inhaling chemical-laden nicotine aerosols suppresses the immune responses in the airways of smokers and e-cigarette users. Some studies, including some at UNC, have detailed how different chemicals in different e-cigarettes, including chemicals that make up thousands of different flavors, have adverse effects on airway cells.

The Jaspers lab, which has been at the forefront of such research, wanted to study the effects of different types of e-cigarettes. For this study, her team collected central respiratory tract (sputum) samples from non-smokers, smokers, and users of both third-generation and fourth-generation e-cigarettes.

Third-generation devices include vape pens and box mods. The fourth generation includes nicotine salt-containing e-cigarettes, such as Juul products, and disposable e-cigarettes, which have become increasingly popular due to restrictions on the sale of Juul products.

Fourth-generation e-cigarette users had significantly more bronchial epithelial cells in their sputum, suggesting airway damage because bronchial epithelial cells normally form an intact barrier in the airways and are not found in sputum samples. Levels of two proteins, sICAM1 and sVCAM1, were significantly lower in fourth-generation e-cigarette users compared to all other groups. These proteins are important in fighting infections and other diseases.

Also, proteins CRP, IFN-g, MCP-1, uteroglobin, MMP-2 and VEGF were significantly lower in fourth versus third generation e-cigarette users, and all of these proteins are important for overall immune defense. So the more these proteins are reduced, the more suppressed our immune system is. “Another key finding of the study was that, when examining the mixture of immune markers in general rather than one at a time, fourth-generation e-cigarette users had the most striking changes of all groups, indicating a shift away from immune homeostasis,” Hickman said.

This study reveals no evidence that e-cigarettes cause cancer, emphysema, COPD, or other long-term illnesses associated with long-term cigarette smoking. But researchers believe that altering immune responses in the airways over many years, especially for teens, could play an important role in the development of long-term health problems and in susceptibility to inhaled pathogens.


Reference magazine:

Hickman, E., et al† (2022) Biomarkers of respiratory immune homeostasis differ significantly with e-cigarette generation. American Journal of Respiratory and Critical Care

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