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

 

Product | Republic Technologies Launches ZIG Nicotine Pouches, Expanding Beyond Traditional Tobacco Accessories
Product | Republic Technologies Launches ZIG Nicotine Pouches, Expanding Beyond Traditional Tobacco Accessories
Republic Technologies UK has entered the nicotine pouch market with ZIG Nicotine Pouches, marking the company’s expansion beyond traditional tobacco-related accessories into smoke-free nicotine products. The product is expected to enter UK retail channels from August 2026, including convenience stores, supermarkets and tobacco retailers. The launch includes six flavors and three nicotine strengths: 8mg, 12mg and 17mg.
Market
Jul.21 by 2Firsts Perspectives
CCPIT Says Trade Friction Index for China-Related Electronics Sector Remains High, With Vape Products Among Areas of Focus
CCPIT Says Trade Friction Index for China-Related Electronics Sector Remains High, With Vape Products Among Areas of Focus
China Council for the Promotion of International Trade (CCPIT) held its July regular press conference on July 31, 2026, releasing the May 2026 Global Economic and Trade Friction Index. CCPIT spokesperson Yang Fan said the global trade friction index stood at 95 in May, remaining at a medium-to-high level. By industry, the electronics sector recorded the highest trade friction index among 13 monitored industries. In China-related trade frictions, the index stood at 93, with electronics products including drones, chips and vape products among areas where friction remained elevated.
Aug.03
Bret Koplow Takes Permanent Charge of FDA Tobacco Center After Pushing Faster PMTA Reviews, as HHS Emphasizes Innovation and Access to Lower-Risk Alternatives
Bret Koplow Takes Permanent Charge of FDA Tobacco Center After Pushing Faster PMTA Reviews, as HHS Emphasizes Innovation and Access to Lower-Risk Alternatives
The U.S. Department of Health and Human Services has named Bret Koplow permanent director of the FDA’s Center for Tobacco Products, ending his period as acting chief. Koplow has spent years working on tobacco regulation, law and policy inside the FDA and, while serving as acting director, pushed for faster PMTA reviews and nicotine pouch review pilots. HHS also said CTP will prioritize innovation and access to less harmful alternatives for adult smokers while continuing efforts to protect youth.
Sep.09
Product | BAT Launches glo Hyper pro+ in Japan, Upgrading the Hyper Platform With Faster Start and Smart Device Management
Product | BAT Launches glo Hyper pro+ in Japan, Upgrading the Hyper Platform With Faster Start and Smart Device Management
British American Tobacco Japan (BAT Japan) has introduced glo Hyper pro+, an upgraded device within the existing glo Hyper platform. The device adds QuickStart™ rapid heating technology, an EasyView™ display and maintenance notification features to improve daily usability. Launched in Japan on July 13, 2026, glo Hyper pro+ maintains compatibility with existing Hyper-format tobacco sticks, including neo, Lucky Strike and KENT.
Jul.30
JUUL2 Sued Within a Week of FDA Authorization as AJ Marketing Alleges Infringement of Programmable Vape Patent
JUUL2 Sued Within a Week of FDA Authorization as AJ Marketing Alleges Infringement of Programmable Vape Patent
Less than a week after JUUL2 received U.S. FDA marketing authorization on August 28, 2026, JUUL Labs was sued for patent infringement in federal court in Delaware. AJ Marketing LLC filed the complaint on September 3, alleging that both JUUL 1 and JUUL2 infringe U.S. Patent No. 8,851,068 B2. The patent covers aspects of programmable electronic vaporization devices, including controls over dose delivery, usage frequency and operating parameters. The plaintiff is seeking reasonable royalties and ongoing royalties tied to the remaining life of the patent. JUUL has not yet publicly responded to the case.
Sep.10
UK PM Andy Burnham Reshapes Vape Retail Rules as Licensing Could Raise Barriers for New Shops
UK PM Andy Burnham Reshapes Vape Retail Rules as Licensing Could Raise Barriers for New Shops
UK Prime Minister Andy Burnham is pushing a high street reform agenda that could give local authorities greater powers over commercial activity, including vape retail. The reforms could involve expanded planning powers and a potential vape retail licensing system, allowing councils to play a larger role in store locations and market access. The measures are part of the UK’s broader shift toward tighter vape regulation, although no nationwide vape retail restrictions have yet been implemented.
Aug.11