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

 

STIIIZY Redesign Fails to Escape PAX Labs Patent Import Ban as Section 337 Case Also Involves China ALD
STIIIZY Redesign Fails to Escape PAX Labs Patent Import Ban as Section 337 Case Also Involves China ALD
U.S. Customs and Border Protection ruled that STIIIZY had not shown that the redesigned cannabis-vape products covered by its latest request fall outside an ITC limited exclusion order tied to PAX Labs patents. CBP accepted some of STIIIZY’s claim-construction and non-infringement arguments, but the company did not address two additional claims in the same patent. Earlier STIIIZY redesigned cartridges and certain associated components imported with them had received separate CBP clearance.
Sep.16
Product | VAPORESSO Launches PRIX MTL Pod, With NFC Version Linking Interchangeable Panels to On-Screen Animations
Product | VAPORESSO Launches PRIX MTL Pod, With NFC Version Linking Interchangeable Panels to On-Screen Animations
VAPORESSO introduced the PRIX MTL pod system in August 2026 in two versions, Filter and NFC. The Filter version allows users to switch between a conventional drip tip and a filter tip, while the NFC version links interchangeable panels to matching on-screen animations. PRIX features a 2,600mAh battery, a 5.5ml pod, a 0.87-inch TFT display and a maximum output of 40W, alongside Dual Mesh Impact Pods capable of operating at two resistance and power configurations. VAPORESSO's French website lists MSRP at $39.99 for the Filter version and $49.90 for the NFC version.
Market
Aug.24 by 2Firsts Perspectives
German Tobacco Tax Revenue Falls 10.8% Through August as Tax-Paid Cigarette Volume Drops 12.6%
German Tobacco Tax Revenue Falls 10.8% Through August as Tax-Paid Cigarette Volume Drops 12.6%
Germany collected €9.789 billion in total tobacco tax revenue from January through August 2026, down 10.8% from a year earlier, according to the Federal Ministry of Finance. Germany's tobacco tax base covers not only cigarettes and fine-cut tobacco but also heated tobacco and vaping liquids taxed as tobacco substitutes. The German Association of the Tobacco Industry and Novel Products, or BVTE, citing federal statistical data, said tax-paid cigarette volume fell 12.6% to 40.6 billion sticks. BVTE is using the latest figures to argue against further tax increases planned from 2027 through 2030, while Germany's parliament is scheduled to hold a first reading of the bill on September 24.
Sep.23
Former Roche Neuroscience and Rare Diseases Communications Director Ria Kioupritzi Joins PMI as Scientific Affairs Director
Former Roche Neuroscience and Rare Diseases Communications Director Ria Kioupritzi Joins PMI as Scientific Affairs Director
Eleftheria (Ria) Kioupritzi, a biopharmaceutical professional with more than 15 years of experience, has joined Philip Morris International as Director Scientific Affairs within Corporate Affairs. She previously served at Roche as Senior Scientific Communications Director for Neuroscience and Rare Diseases and worked extensively in spinal muscular atrophy. Her earlier career also covered competitive intelligence, clinical and regulatory monitoring, pipeline development and launch preparation. During her time working in Roche's SMA field, Evrysdi passed through several U.S. FDA milestones, including its initial approval, an expanded indication for younger infants and approval of a tablet formulation. Public records do not show that Kioupritzi herself led the FDA submissions.
Sep.22
FDA Authorizes JUUL2, Cites Adult Switching Amid Efforts to Speed PMTA Reviews
FDA Authorizes JUUL2, Cites Adult Switching Amid Efforts to Speed PMTA Reviews
The FDA authorized the JUUL2 device and tobacco- and menthol-flavored pods on Aug. 28, bringing the number of authorized e-cigarette products to 48. The agency highlighted complete switching among adult smokers, with six-week switching rates reaching 28.4%–49.3% for the menthol pod. The decision comes as FDA works to speed PMTA reviews, reduce application backlogs and expand authorized e-cigarette and nicotine-pouch products while maintaining enforcement priorities for unauthorized products.
Regulations
Aug.29
Juul Displays FDA-Authorized JUUL2, Highlights Age Verification at NACS Show 2026
Juul Displays FDA-Authorized JUUL2, Highlights Age Verification at NACS Show 2026
At the 2026 NACS Show in Las Vegas, Juul Labs displayed its JUUL2 e-cigarette system alongside existing products, age-verification messaging and mobile coupons, 2Firsts observed. The JUUL2 device and Virginia Tobacco and Polar Menthol pods received FDA marketing authorization in August 2026. Booth materials highlighted longer battery life, greater e-liquid capacity and connected-device features. A TruAge sign and a mobile coupon presentation also featured at the booth, with weekly offers available to age-verified adult nicotine consumers at participating retailers.
EXPO
Oct.09