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

 

U.S. Appeals Court Says BAT Must Face Class Action Over Cigarette Labels
U.S. Appeals Court Says BAT Must Face Class Action Over Cigarette Labels
A U.S. appeals court ruled that British American Tobacco (BAT) must continue facing a consumer class action lawsuit over cigarette labels. The ruling allows the case to proceed but does not determine that BAT violated the law or is liable for damages. The case highlights ongoing legal risks facing major tobacco companies related to product labeling, consumer disclosures and product liability claims.
Jul.31
Special Report | Russia, Ukraine and Belarus Launch Fresh Push to Rein in Vaping
Special Report | Russia, Ukraine and Belarus Launch Fresh Push to Rein in Vaping
Russia, Ukraine and Belarus are tightening vape regulation through different tools, from Ukraine’s stronger enforcement push and Belarus’s proposed advertising restrictions to Russia’s new GOST standard and regional sales-ban mechanism. As black-market concerns persist, some Russian experts argue that China’s tightly controlled but legalised model — built around licensing, traceability and taxation — may offer a more effective alternative to blanket prohibition.
Jul.15
Charlie’s Plans Q3 2026 Pilot of America’s First Age-Gated Flavored Disposable Vape
Charlie’s Plans Q3 2026 Pilot of America’s First Age-Gated Flavored Disposable Vape
U.S. vape company Charlie’s Holdings announced plans to pilot its age-gated flavored disposable vape products in hundreds of retail stores during the third quarter of 2026. The company said the products will utilize AI- and blockchain-powered age-verification technology designed to address FDA concerns over youth access and potentially create a new compliance pathway for flavored vape products.
Jun.15
Reuters: Shopify May Ban All Vape Sales This Week Amid Illegal Market Crackdown
Reuters: Shopify May Ban All Vape Sales This Week Amid Illegal Market Crackdown
Reuters reported that Shopify may ban all vape products from its platform as soon as this week, signaling that U.S. enforcement against the illegal vape market is expanding from retailers and importers to e-commerce platforms and payment networks.
MarketBAT
Jun.23 by 2Firsts Perspectives
Trump’s Tobacco Investments and Industry Donations Draw Scrutiny as FDA Eases Vape and Nicotine Pouch Rules
Trump’s Tobacco Investments and Industry Donations Draw Scrutiny as FDA Eases Vape and Nicotine Pouch Rules
A report by KFF Health News says that as the Trump administration pursued a series of policies favorable to the nicotine and tobacco industry, President Donald Trump increased his holdings in tobacco companies while benefiting from substantial industry-linked political donations, prompting questions from public health advocates about potential conflicts of interest and regulatory direction.
Jun.12
ATF Cancels Webloc Contract, Raising Questions Over Commercial Location Data in Enforcement
ATF Cancels Webloc Contract, Raising Questions Over Commercial Location Data in Enforcement
The U.S. Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) has stopped using Webloc, a commercial phone-tracking tool, after lawmakers, a prosecutor and a judge raised legal and privacy concerns over warrantless use of ad-tech location data, a development that may affect data-use boundaries in U.S. enforcement against illicit tobacco, nicotine products and cross-border distribution networks.
Jun.29