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

 

Turning Point Brands Reports Q1 2026 Net Sales of $124.3 Million as Modern Oral Net Sales Rise 133%
Turning Point Brands Reports Q1 2026 Net Sales of $124.3 Million as Modern Oral Net Sales Rise 133%
Turning Point Brands reported first-quarter 2026 results on May 7, covering the period ended March 31, 2026. Total consolidated net sales were $124.3 million, up 16.8% year on year. Gross profit was $68.3 million, up 14.6%, while net income fell 19.0% to $11.7 million. Adjusted EBITDA declined 6.5% to $25.9 million.
May.08 by 2FIRSTS.ai
State Registries Are Reshaping U.S. Vape Market Access 2Firsts Interview with U.S. Vapor Manufacturers Association President Allison Boughner
State Registries Are Reshaping U.S. Vape Market Access 2Firsts Interview with U.S. Vapor Manufacturers Association President Allison Boughner
As the U.S. vapor market faces FDA authorizations, import seizures and growing state-level restrictions, AVM President Allison Boughner told 2Firsts that state product registries and white-list systems are having the most immediate impact. She said distributors are placing greater weight on documentation, product origin and supply-chain transparency.
Special Report
May.26
Shunhao Shares Reports 2025 Revenue of RMB 1.188 Billion, While Q1 2026 Net Profit Rises 49.94% and New Tobacco Operations Continue
Shunhao Shares Reports 2025 Revenue of RMB 1.188 Billion, While Q1 2026 Net Profit Rises 49.94% and New Tobacco Operations Continue
Shunhao Shares’ 2025 annual report summary and first-quarter 2026 report show that the company recorded 2025 revenue of RMB 1.188 billion, down 21.78% year on year, while net profit attributable to shareholders rose 30.00% to RMB 58.94 million. In the first quarter of 2026, revenue was RMB 291.51 million, down 10.34% year on year, while attributable net profit rose 49.94% to RMB 19.98 million.
Apr.29 by 2FIRSTS.ai
Geneva Court Annuls Ban on Disposable E-Cigarette Sales, Says Power Lies With Federal Authorities
Geneva Court Annuls Ban on Disposable E-Cigarette Sales, Says Power Lies With Federal Authorities
The Geneva Court of Justice on Tuesday upheld appeals filed by four associations and companies active in the tobacco trade and annulled the Geneva legal provision banning the sale of disposable e-cigarettes, commonly known as “puffs.”
Apr.30 by 2FIRSTS.ai
Special Report| War continues to shape the Ukrainian tobacco market
Special Report| War continues to shape the Ukrainian tobacco market
Four years into the war, Ukraine’s tobacco market is being reshaped by stress-driven consumption, tax pressure, youth e-cigarette use and a growing illicit segment. Surveys point to rising tobacco and nicotine product use, while higher excise duties and shadow trade are adding new complexity to the market.
Apr.17
Kentucky Governor Signs Tobacco, Nicotine, and Vapor Product Licensing Bill Into Law
Kentucky Governor Signs Tobacco, Nicotine, and Vapor Product Licensing Bill Into Law
A Kentucky bill relating to tobacco, nicotine, and vapor product licensing was signed by the governor on April 10, 2026, and enacted as Acts Chapter 70. The measure sets application requirements for tobacco, nicotine, and vapor product licenses, governs batch licensing, renewals, ownership changes, and denial grounds, and requires the Department of Alcoholic Beverage Control to publish application forms and related regulations within 30 days of the law’s effective date.
Apr.14 by 2FIRSTS.ai