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

 

Innovation, Insights and Networking: NUBIZ Brings the Global NGP Industry Together in Dortmund
Innovation, Insights and Networking: NUBIZ Brings the Global NGP Industry Together in Dortmund
The market for next-generation products is expanding rapidly, with vapes, e-cigarettes, pouches, snus and heat-not-burn products among the industry’s most innovative segments. As part of InterTabac, NUBIZ provides a central platform for reduced-risk tobacco and nicotine products, bringing together global leaders and newcomers from 15 to 17 September. The show combines market insights, product comparisons, networking, a high-level conference programme and exclusive side events.
Jun.03
Malaysian Tobacco Control Groups Call for Annual 5% Tobacco Tax Hike
Malaysian Tobacco Control Groups Call for Annual 5% Tobacco Tax Hike
According to The Star and The Edge Malaysia, tobacco control groups in Malaysia have urged the government to raise tobacco taxes by at least 5% annually, saying the measure could reduce smoking rates and fund public health and social programmes.
News
May.26
2Firsts Hosts UK Vape Duty Stamp Compliance Exchange in Shenzhen
2Firsts Hosts UK Vape Duty Stamp Compliance Exchange in Shenzhen
2Firsts held a UK vape duty stamp compliance exchange in Shenzhen on May 14, bringing together representatives from nearly 20 companies. The session addressed Vaping Products Duty, duty stamp applications, UK agency qualifications and warehousing, while introducing 2Firsts Compliance Solutions’ UK service.
Events
May.17
2Firsts Data|China Vape Exports Sink to Three-Year April Low After Tax Rebate Ends, Falling to $694 Million
2Firsts Data|China Vape Exports Sink to Three-Year April Low After Tax Rebate Ends, Falling to $694 Million
China’s e-cigarette export value declined to $694 million in April 2026, marking the lowest April level in the past three years. The data is notable because April was the first full month after China removed export VAT rebates for certain e-cigarette products. Compared with April 2025, export value fell 20.9%; compared with April 2024, it was down 22.3%. Month-on-month, exports dropped 23.2% from March 2026.
Special Report
May.23
Haypp Report Shows Nicotine Pouches Gaining Ground as a Vape Alternative in the UK
Haypp Report Shows Nicotine Pouches Gaining Ground as a Vape Alternative in the UK
According to Haypp’s 2026 UK Nicotine Report, nicotine pouches are increasingly replacing both cigarettes and vaping. The UK market grew sharply, with Haypp and Northerner reporting a 60% year‑on‑year sales increase in 2025. Notably, 40% of users adopted pouches to quit vaping, nearly matching the 43% who used them to stop smoking. This indicates pouches are expanding beyond traditional smoking cessation and gaining traction among adults seeking non‑inhalable nicotine alternatives.
Jul.01
Product | OLIVEBAR Launches RAZ PRO 85K, Combining Up to 85,000 Puffs With a Transparent Pod Design
Product | OLIVEBAR Launches RAZ PRO 85K, Combining Up to 85,000 Puffs With a Transparent Pod Design
OLIVEBAR has introduced the RAZ PRO 85K disposable vape, featuring up to 85,000 puffs, a transparent e-liquid pod, and a Mega HD display. As competition in the ultra-high-puff disposable segment continues to intensify, the new device reflects an industry shift from simply increasing puff counts toward enhancing visual interaction and user experience.
Jul.03