Fourth-generation Vaping Devices Increase Risk to Immune Cells

Innovation
Jul.01.2022
With the FDA ordering Juul to stop selling their e-cigarette devices, UNC School of Medicine researchers led by Ilona Jaspers, PhD, published the first study to compare the respiratory immune health effects of different types of devices.

CHAPEL HILL, NC – 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 inside our airways, according to a new peer-reviewed paper from UNC School of Medicine researchers led by toxicologist Ilona Jaspers, PhD, director of the UNC Center for Environmental Medicine, Asthma, and Lung Biology and director of the UNC Curriculum in Toxicology and Environmental Medicine.

 

Fourth-generation Vaping Devices Increase Risk to Immune Cells
Ilona Jaspers, PhD

 

Lead author Elise Hickman, PhD, a recent graduate from Jaspers’ lab, and colleagues, who published their research in the American Journal of Respiratory and Critical Care 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 Jaspers, professor of pediatrics and microbiology and immunology. “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.”

 

Electronic cigarettes have increased in popularity over the past decade. Some people began using them as a means to quit smoking, thinking vaping was a safer alternative, both in the short-term and long-term. Also, because electronic cigarettes lack 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,” Jaspers said. “It took 60 years of research to show that smoking causes cancer.” E-cigarettes have 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 defenses in people who vape that, frankly, we’ve never seen before, which is very concerning.”

 

Most concerning to 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 – a drug with its own health implications even beyond addiction – and thousands of chemicals, many of which the 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 flavors, 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.

 

Third-generation devices 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 following restrictions on the sale of Juul products.

 

Fourth-generation e-cigarette users had significantly more bronchial epithelial cells in their sputum, and this suggests 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.

 

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 diminished these proteins are, the more suppressed our immune systems are. “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 Hickman.

 

This research does not reveal evidence 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.

 

The National Institutes of Health funded this research.

 

Elise Hickman, who earned an Impact Award from the UNC Graduate School, is the first author of the paper, and Ilona Jaspers is the senior author. Other authors are Alexis Payton, Parker Duffney, Heather Wells, Agathe S. Ceppe, Stephanie Brocke, Aleah Bailey, Meghan E. Rebuli, Carole Robinette, Brian Ring, Julia E. Rager, and Neil E. Alexis.

 

Also read:

FDA Denies Authorization to Market JUUL Products

 

From Brands to Supply Chains: 2Firsts Builds a PMTA Compliance Service System for the U.S. Market
From Brands to Supply Chains: 2Firsts Builds a PMTA Compliance Service System for the U.S. Market
2Firsts supports new tobacco and nicotine companies entering the U.S. market with full-chain PMTA compliance services.
Jun.04
Special Report | Russian Vape Compromise Faces First Hurdles
Special Report | Russian Vape Compromise Faces First Hurdles
Russia’s regional vape-ban model is facing early legal and political tests, as Perm Krai moves ahead before federal legislation is fully adopted. The case highlights uncertainty over regional authority, concerns from business groups about market fragmentation, and the risk that pressure against regional bans could revive calls for a stricter nationwide prohibition.
Industry Insight
May.28
Imperial Brands Explains What the UK Tobacco and Vapes Act 2026 Means for Retailers
Imperial Brands Explains What the UK Tobacco and Vapes Act 2026 Means for Retailers
Imperial Brands has outlined what the newly approved UK Tobacco and Vapes Act 2026 means for retailers. The legislation received Royal Assent on April 29, 2026, and gives the Government powers to extend tobacco-style regulation to a wider range of products, including vaping products, heated tobacco, nicotine pouches and cigarette papers. Imperial Brands emphasized that most measures will be introduced in phases rather than taking effect immediately.
May.11 by 2FIRSTS.ai
UK Bill Banning Tobacco Sales to People Born After 2008 Clears Parliament
UK Bill Banning Tobacco Sales to People Born After 2008 Clears Parliament
A UK bill banning the legal sale of tobacco to people born on or after January 1, 2009 has completed its passage through parliament. Under the bill, those born in that group will never be able to be legally sold tobacco anywhere in the UK. The legislation is expected to receive royal assent next week. It also gives ministers powers to strengthen public-place smoking restrictions and restricts branding, promotion and advertising of vape and nicotine products aimed at children.
Apr.22 by 2FIRSTS.ai
Australian State Targets Illegal Tobacco Retailers With Tougher Closure Powers
Australian State Targets Illegal Tobacco Retailers With Tougher Closure Powers
According to Reuters, Australia’s state of Victoria introduced legislation to give police and the state tobacco licensing regulator stronger powers to shut businesses selling illegal tobacco, with non-compliant operators facing fines of more than A$2.4 million and up to 20 years in prison.
Jun.05
French Lawmakers Move to Extend Plain Packaging Rules to Vaping Product
French Lawmakers Move to Extend Plain Packaging Rules to Vaping Product
French lawmakers Nicolas Thierry and Pierre Cazenave said on April 15 that they will file a cross-party bill to extend plain packaging requirements to vaping products. Under the proposal, unit packs and outer packaging for vaping products, including those without nicotine, would become neutral and standardized in the same way cigarette packs have been since 2017.
Apr.16 by 2FIRSTS.ai