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 | FOGER Introduces Switch Pro 30K Nixodine Pod in U.S. Retail, Bringing 6-MN Related Formulation to High-Capacity Pod Platform
Product | FOGER Introduces Switch Pro 30K Nixodine Pod in U.S. Retail, Bringing 6-MN Related Formulation to High-Capacity Pod Platform
FOGER has introduced the Switch Pro 30K Nixodine Pod in U.S. retail channels, bringing a 6-methylnicotine (6-MN)-related formulation into its reusable Switch Pro 30K pod ecosystem. The product retains the existing reusable dock and magnetic replacement pod architecture, featuring a 19ml prefilled pod, dual-mesh heating and Normal/Boost modes. The Nixodine version is labeled nicotine-free in terms of conventional nicotine but uses a 5% Nixodine-related formulation. The product has appeared in U.S. retail and wholesale channels, with some listings indicating Kentucky-only availability.
Aug.28
China’s Shanghai Tobacco Group Launches CNY 10.98 Million (Approximately US$1.53 Million) Procurement for Heated Tobacco Production Utility Equipment
China’s Shanghai Tobacco Group Launches CNY 10.98 Million (Approximately US$1.53 Million) Procurement for Heated Tobacco Production Utility Equipment
Shanghai Tobacco Group Co., Ltd., a tobacco manufacturing company under China National Tobacco Corporation (CNTC), has launched a public tender for heated tobacco products (HTPs) production utility equipment at its Shanghai Cigarette Factory. The project is valued at CNY 10.98 million and covers six combined air-conditioning units, electrical cabinets and control systems for production facilities. The procurement includes equipment design, supply, installation, commissioning and related training services.
Aug.07
Product | JNR Launches Shisha Hookah 70K E-Hookah With 60ml E-Liquid and 0.6% Nicotine
Product | JNR Launches Shisha Hookah 70K E-Hookah With 60ml E-Liquid and 0.6% Nicotine
JNR has introduced the Shisha Hookah 70K, a high-capacity rechargeable disposable vape designed around a hookah-inspired experience. The device comes prefilled with 60ml of e-liquid at 6mg/ml (0.6%) nicotine strength, alongside a 1,000mAh rechargeable battery and a 0.38Ω single mesh coil. It also features adjustable airflow and battery and e-liquid level displays. JNR claims the device can deliver up to 70,000 puffs and offers more than 20 flavors. Retail listings for the product have appeared in markets including Tunisia.
Market
Aug.24 by 2Firsts Perspectives
EU ‘TPD3’ Enters Next Phase on Aug. 14 as Fragmented Vape and Nicotine Pouch Rules Push the Single Market Toward Regulatory Overhaul
EU ‘TPD3’ Enters Next Phase on Aug. 14 as Fragmented Vape and Nicotine Pouch Rules Push the Single Market Toward Regulatory Overhaul
A 12-week European Commission consultation on revising the Tobacco Products Directive and Tobacco Advertising Directive is due to close on Aug. 14, 2026. The Commission has identified e-cigarette flavours, disposable vapes, tobacco heating devices, nicotine pouches, nicotine-free e-cigarettes, packaging and digital marketing among areas for possible new EU rules. National regulations already vary significantly across the bloc, a fragmentation the Commission says creates internal-market barriers and distorts competition. No formal revised TPD/TAD legislative text has yet been published, with the Commission currently indicating December 2026 for the legislative initiative.
Aug.14
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
China Tobacco Plans CNY 60 Billion Investment in ICBC, Agricultural Bank as Strategic Ties Extend Beyond Equity
China Tobacco Plans CNY 60 Billion Investment in ICBC, Agricultural Bank as Strategic Ties Extend Beyond Equity
China National Tobacco Corporation and several subsidiaries plan to invest a combined CNY 60 billion ($8.7 billion) in share placements by Industrial and Commercial Bank of China and Agricultural Bank of China as strategic investors. The agreements extend beyond equity investment to corporate governance, banking services and supply-chain finance. The filings also disclose 2025 data on China Tobacco’s tax and profit contributions and industry scale.
Sep.07