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 | Unique Serial Number + Custom Design: Vuse Launches McLaren F1 Team Limited-Edition Vape
Product | Unique Serial Number + Custom Design: Vuse Launches McLaren F1 Team Limited-Edition Vape
Vuse has launched a McLaren Racing co-branded limited-edition vape, the Vuse Ultra x McLaren F1 Team Limited Edition, on its official website. Based on the standard Vuse Ultra, the device features design elements including McLaren’s “Racing Papaya” orange, and comes with wireless charging and two replaceable batteries. The product is priced at £45.
Dec.18 by 2FIRSTS.ai
U.S. FDA Unveils Next-Generation Agentic AI Tool to Boost Review and Regulatory Efficiency
U.S. FDA Unveils Next-Generation Agentic AI Tool to Boost Review and Regulatory Efficiency
The U.S. FDA has announced the agency-wide deployment of new agentic AI capabilities, providing all employees with an optional multi-step task automation tool. Building on the broad adoption of its earlier large-language-model system, Elsa, the FDA aims to use this next-generation AI workflow to accelerate product review, regulatory oversight, and internal operations, while maintaining strict human supervision and data security.
Dec.02 by 2FIRSTS.ai
Australia’s TGA Seizes Illicit Vaping Products Worth Over  US$670,000 in Bendigo
Australia’s TGA Seizes Illicit Vaping Products Worth Over US$670,000 in Bendigo
Australia’s Therapeutic Goods Administration (TGA) has seized illicit vaping products with an estimated street value exceeding A$1 million (approximately US$670,000) following an enforcement operation in Bendigo, Victoria.
Dec.24 by 2FIRSTS.ai
China Business Journal Reports: Multiple New E-Cigarette Policies Enter Public Consultation Phase in China, Covering Capacity Control and Credit Management
China Business Journal Reports: Multiple New E-Cigarette Policies Enter Public Consultation Phase in China, Covering Capacity Control and Credit Management
China Business Journal, citing a review of policy documents released by the State Tobacco Monopoly Administration in early 2026, said China’s latest e-cigarette rules target credit-based regulation, capacity controls and national standards revisions.Alan Zhao, co-founder of 2Firsts, said tighter oversight will speed consolidation, curb noncompliance and reduce destructive competition.
Jan.12 by 2FIRSTS.ai
JUUL Files ITC Complaint over Vaporizer Device Infringement
JUUL Files ITC Complaint over Vaporizer Device Infringement
The U.S. International Trade Commission has instituted a Section 337 investigation following a complaint filed by JUUL Labs, Inc. and VMR Products LLC. The complaint alleges that certain vaporizer devices, cartridges and related components infringe two U.S. patents. The investigation covers importation, sale for importation and post-importation sales in the United States, with the complainants seeking a limited exclusion order and cease and desist orders.
Dec.19 by 2FIRSTS.ai
Police dismantle a network of 50+ stores selling unmarked nicotine products in the Moscow region
Police dismantle a network of 50+ stores selling unmarked nicotine products in the Moscow region
TASS reported that police dismantled a distribution network in the Moscow region selling nicotine-containing products, e-cigarettes and vapes without mandatory markings, with organizers earning more than 10 million rubles per month (more than about $130,000). Interior Ministry spokesperson Irina Volk said some items were labeled with counterfeit identification tools of the Chestny Znak system, while others had no codes.
Dec.30 by 2FIRSTS.ai