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

 

UK Councils Seize More Than 1.3 Million Non-Compliant Vapes One Year After Disposable Ban
UK Councils Seize More Than 1.3 Million Non-Compliant Vapes One Year After Disposable Ban
One year after the UK disposable vape ban came into force, local authorities continue to seize illegal and non-compliant vaping products. FOI data compiled by nicotine retailer Northerner shows more than 1.3 million products were seized between June 2025 and May 2026, with Bolton recording the highest number of seizures and Swansea reporting the highest estimated value.
Jul.21
China Tobacco Hubei Industrial Patent Discloses Nicotine Tooth Patch for Fixed Oral Delivery
China Tobacco Hubei Industrial Patent Discloses Nicotine Tooth Patch for Fixed Oral Delivery
According to Chinese patent records, a “nicotine tooth patch” application filed by China Tobacco Hubei Industrial Corporation (CTHB) and Hubei Xinye Tobacco Sheet Development Co., Ltd. was published on May 19, 2026. The filing proposes a nicotine gel patch that adheres to the tooth surface, especially the lingual side, to reduce displacement, foreign-body sensation, and accidental swallowing risks associated with existing oral nicotine products.
Jun.10
Illicit Vape and Nicotine Pouch Seizures Concentrated in UK Hotspots, New Data Shows
Illicit Vape and Nicotine Pouch Seizures Concentrated in UK Hotspots, New Data Shows
Freedom of Information (FOI) data from the UK shows that more than 3,000 seizures of illegal nicotine products were recorded in the 2024/25 financial year, with Hull, Liverpool and Bolton emerging as the most active enforcement hotspots — highlighting that the problem of illicit vapes, nicotine pouches and smokeless tobacco products persists across many parts of the country.
Jun.16
Canada Recalls Siberia and ZYN Nicotine Pouches Over Unauthorized Sales
Canada Recalls Siberia and ZYN Nicotine Pouches Over Unauthorized Sales
Health Canada has issued a nationwide recall for nicotine pouch products sold under the Siberia and ZYN brands, citing a lack of market authorization. All affected lots are subject to the recall.
Jun.15
Germany Expands Take-Back Rules for Disposable Vapes From July 1
Germany Expands Take-Back Rules for Disposable Vapes From July 1
Germany has expanded take-back obligations for disposable vapes from July 1, 2026, requiring consumers to be able to return used devices at stores that sell such products, including kiosks, petrol stations and vape shops, as e-cigarette regulation extends from sales to waste management and lithium-battery safety.
Market
Jul.06 by 2Firsts Perspectives
Product | VEEV One Plus Goes Official as PMI Strengthens Its Closed-Pod Vaping Portfolio
Product | VEEV One Plus Goes Official as PMI Strengthens Its Closed-Pod Vaping Portfolio
Philip Morris International (PMI) has officially introduced the VEEV One Plus, the next-generation device in its closed-pod vaping lineup. The product is now featured on the official VEEV website in Portugal, bringing hardware upgrades including a new dual-pod storage system, a larger battery, and an updated device design while maintaining compatibility with existing VEEV One pods.
Jul.02