Airway Immune Risks of Fourth Generation e-Cigarettes

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Fourth-generation e-cigarettes, such as Juul devices, are associated with unique changes in markers of immune responses inside our airways, according to a new peer-reviewed paper in the American Journal of Respiratory and Critical Care Medicine.

Third-generation e-cigarettes include vape pens and box mods. Fourth generation include nicotine-salt-containing e-cigarettes, such as Juul products, and disposable e-cigarettes, which have become increasingly popular, especially after the recent FDA ban on the sale of Juul products.

Researchers in the lab of Professor Ilona Jaspers at the UNC School of Medicine found that users of fourth-generation nicotine-salt-containing devices display a unique mix of cellular biomarkers indicative of immune suppression.

“Our work demonstrates the importance of considering device type in future clinical, epidemiological, and mechanistic studies on the health effects of e-cigarettes,” said Prof Jasper, who led the study. “We also think this research can help regulators determine which products cause the most severe types of biological changes in airway cells important for maintaining proper health.”

E-cigarettes have become popular in the last decade. Some started used them to quit smoking, believing vaping was a safer alternative, both in the short-term and long-term. Also, because electronic cigarettes don’t contain tar, consumers assumed vaping decreased their risk of cancer down the road.

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

A major concern for researchers, doctors, and public health officials is the fact that teenagers who would not have otherwise tried cigarettes began using e-cigarettes, which contain nicotine – with its attendant health implications – and thousands of chemicals, many of which are FDA-approved for eating but not inhaling.

Several studies have documented that inhaling chemical-laden nicotine aerosols suppresses the immune responses in the respiratory tracts of smokers and e-cigarette users. Some studies, including some at UNC, have detailed how different chemicals in various e-cigarettes, including chemicals that make up thousands of different flavours, have adverse effects on airway cells. The Jaspers lab, which has been at the forefront of such research, set out to study the effects of different varieties of e-cigarette devices. For this study, her team collected central airway (sputum) samples from non-smokers, smokers, and users of both third-generation and fourth-generation e-cigarette devices.

They found that users of fourth-generation e-cigarettes had significantly more bronchial epithelial cells in their sputum, suggestive of airway injury because normally, bronchial epithelial cells make up 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 disease.

In addition, proteins are important for overall immune defence were significantly lower in fourth versus third generation e-cigarette users. Lower of these proteins – CRP, IFN-g, MCP-1, uteroglobin, MMP-2, and VEGF – indications immune system depression. “Another key finding of the study was that, when examining the mixture of immune markers overall rather than one by one, fourth generation e-cigarette users had the most distinguishable changes out of all of the groups, indicating a shift away from immune homeostasis,” said the study’s lead author, Elise Hickman, PhD.

The study did not demonstrate that e-cigarettes cause cancer, emphysema, COPD, or other long-term diseases associated with long-term cigarette smoking. But researchers think that altering immune responses in the respiratory tract over the course of many years, especially for teens, could play a major role in the development of long-term health conditions and in susceptibility to inhaled pathogens.

Source: University of North Carolina