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

 

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
KT&G’s Lil Strengthens Market Lead in Korea as Heated Tobacco Share Reaches 47.4%
KT&G’s Lil Strengthens Market Lead in Korea as Heated Tobacco Share Reaches 47.4%
According to South Korea’s UpKorea, KT&G’s heated tobacco brand Lil reached a 47.4% share of Korea’s heated tobacco stick market in the first quarter of 2026. The company is expanding its next-generation products (NGP) business through product development, technology investment and overseas growth. KT&G reported NGP sales of 890.1 billion won (approximately US$650 million) in 2025, up significantly from 279.3 billion won in 2020. Lil products are now available in 34 markets, while KT&G continues building its technology portfolio through patents and multiple product platforms.
Jul.23
How AI Is Rewriting the Talent Playbook for the Nicotine Industry: JTI’s Case
How AI Is Rewriting the Talent Playbook for the Nicotine Industry: JTI’s Case
AI is moving from a back-office tool to a core organizational capability in the nicotine industry. Based on JTI’s responses, this 2Firsts feature examines how AI is reshaping talent strategy, internal mobility, decision-making and human accountability as global tobacco companies compete in the shift toward new nicotine categories.
Jun.17
FDA Sued Over Allowing Some Unauthorized Vapes and Nicotine Pouches to Stay on Market
FDA Sued Over Allowing Some Unauthorized Vapes and Nicotine Pouches to Stay on Market
Public health groups, pediatricians and parents sued the U.S. Food and Drug Administration on July 14, 2026, challenging a May enforcement guidance that they say allows unauthorized e-cigarettes and nicotine pouches to remain on the market while applications are under review.
Jul.15
Product | APUS Launches Chloe 50K, Bringing Purse-Inspired Design to the U.S. High-Puff Disposable Market
Product | APUS Launches Chloe 50K, Bringing Purse-Inspired Design to the U.S. High-Puff Disposable Market
APUS has introduced the Chloe 50K disposable vape, which has appeared across U.S.-facing online retail channels including Element Vape and Vapesourcing. The device combines a purse-inspired body and chain attachment with a 20ml e-liquid capacity, 1,250mAh rechargeable battery, dual mesh coil, and battery and e-liquid indicators. It is rated for up to 50,000 puffs. The product does not appear on the FDA’s current list of authorized e-cigarettes, and U.S. retail availability does not indicate FDA marketing authorization.
Jul.15
FDA Tobacco Proposal Signals Full-Chain Compliance Test for Global E-Cigarette Supply Chains
FDA Tobacco Proposal Signals Full-Chain Compliance Test for Global E-Cigarette Supply Chains
FDA’s proposed foreign tobacco establishment registration and product listing rule remains unfinished, but Accorto told 2Firsts it reflects a shift toward structured oversight similar to medical device and pharmaceutical compliance frameworks. For Chinese and global e-cigarette suppliers, U.S. market access is moving beyond product authorization toward full-chain compliance covering manufacturing, documentation, import control, distribution, retail and marketing discipline.
Special Report
Jul.09