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

 

IQOS Global Flagship Space to Open in Tokyo Ginza as PMI Expands Consumer Experience Strategy
IQOS Global Flagship Space to Open in Tokyo Ginza as PMI Expands Consumer Experience Strategy
Philip Morris Japan (PMJ) announced that it will open “IQOS Flagship Ginza” in Tokyo on September 4, 2026. The location will become the first global flagship space for PMI’s IQOS brand. PMJ said the venue will target adult smokers aged 20 and above and combine product experiences, community engagement and local cultural elements. The design will incorporate Japanese natural aesthetics and traditional craftsmanship. The launch reflects PMI’s broader strategy of strengthening consumer engagement through experiential retail and brand spaces. The existing IQOS Store Ginza is scheduled to close on August 30, 2026.
Jul.21
Italian Court Ends Six-Year Cigarette Excise Dispute, Rejecting Damages Claim
Italian Court Ends Six-Year Cigarette Excise Dispute, Rejecting Damages Claim
Italy’s Lazio Regional Administrative Court has dismissed an appeal by Italian Tobacco Manufacturing and Manifattura Italiana Tabacco over the cigarette excise calculation mechanism, upholding the minimum tax burden rules and excluding compensation for smaller tobacco operators.
News
Jun.26 by 2Firsts Perspectives
French Vape Market Under Pressure as Europe’s First Listed Vape Company Kumulus Vape Reports 7.8% H1 Revenue Decline, Retail Sales Rise 41.5%
French Vape Market Under Pressure as Europe’s First Listed Vape Company Kumulus Vape Reports 7.8% H1 Revenue Decline, Retail Sales Rise 41.5%
Kumulus Vape, Europe’s first publicly listed vape company, reported a 7.8% year-on-year decline in first-half 2026 revenue. Amid changing conditions in France’s vape market, the company said channel diversification helped offset pressure, with physical store sales increasing 41.5% year on year. Listed on Euronext Access Paris in 2019 and later transferred to Euronext Growth Paris, Kumulus Vape is viewed as a representative company of Europe’s vape sector. Its performance highlights the industry’s shift from rapid expansion toward more operationally focused growth.
Jul.27
2Firsts Data | China’s U.S. Vape Exports Have Yet to Regain Previous Growth Momentum in H1 2026, but Hardware Grew 15.2% and 6-Methyl Nicotine-Related Products Rose 234.7%
2Firsts Data | China’s U.S. Vape Exports Have Yet to Regain Previous Growth Momentum in H1 2026, but Hardware Grew 15.2% and 6-Methyl Nicotine-Related Products Rose 234.7%
China’s vape exports to the U.S. reached approximately $1.58 billion in the first half of 2026, remaining broadly stable from a year earlier but still below previous growth momentum. 2Firsts’ analysis of China Customs data shows that the U.S. market has not simply returned to its previous trajectory after the enforcement shock and inventory-driven swings of 2025. Instead, export momentum is shifting across product categories. Vaping devices and atomization hardware increased 15.2% year over year, while 6-methyl nicotine-related and other nicotine substitute products surged 234.7%. Meanwhile, traditional nicotine-containing vaping products continued to face pressure.
Jul.22
U.S. FDA: Youth E-Cigarette Prevention Campaign Prevented About 444,000 Initiations and Reduced Illegal Vape Sales
U.S. FDA: Youth E-Cigarette Prevention Campaign Prevented About 444,000 Initiations and Reduced Illegal Vape Sales
The U.S. Food and Drug Administration (FDA) said its youth e-cigarette prevention campaign, “The Real Cost,” prevented about 444,000 U.S. youth from starting e-cigarette use between 2023 and 2024 and blocked more than $42 million in unauthorized e-cigarette sales that would have been used by youth.
Market
Jun.25
Data|China’s May Vape Exports Fall 10.3%; January–May Shipments Slip 0.9%
Data|China’s May Vape Exports Fall 10.3%; January–May Shipments Slip 0.9%
China’s vape-related exports fell 10.25% year on year in May 2026, marking a second consecutive monthly decline, although exports recovered modestly from April. January-May exports totaled US$4.018 billion, down 0.86% from a year earlier and broadly in line with 2025 levels.
Special Report
Jun.29