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

 

From Vuse, Velo and glo to AI Consulting: Former BAT Content Lead Launches Destreza
From Vuse, Velo and glo to AI Consulting: Former BAT Content Lead Launches Destreza
Former BAT global content lead Andy Parton has left the company and launched Destreza, a London-based AI-native marketing consultancy. Parton previously worked across BAT's New Category brands Vuse, Velo and glo and had also served as Global Brand Lead for Vuse Go. Destreza says it will advise consumer businesses on AI in brand strategy, operating models, capability and agency configuration, using specialist AI agents to support research, strategy and creative development. BAT reported £3.621 billion in New Category revenue in 2025.
Sep.22
South Korea Imports 12,126 Kg of Nicotine Analogues From April to August After Bringing Synthetic Nicotine Under Tobacco Law
South Korea Imports 12,126 Kg of Nicotine Analogues From April to August After Bringing Synthetic Nicotine Under Tobacco Law
South Korea's liquid-vape market is showing changes across raw-material imports, product types and sales channels after synthetic nicotine came under the Tobacco Business Act on April 24. Customs data show nicotine-analogue imports totaled 12,126 kilograms from April through August, while synthetic-nicotine imports over the same five months totaled 231,663 kilograms, just 39.3% of the amount imported in March alone. Physical liquid-vape stores tracked in Seoul and Gyeonggi Province fell 9.9%, unmanned outlets edged higher and online sales listings increased from 27,774 to 42,437. Government testing of 105 liquid inhalation products promoted as nicotine-free separately found nicotine in 13 and 6-methylnicotine in 12.
Sep.22
Product | OXVA Introduces XLIM PRO 4 With Liquid-Level Anti-Burn Technology and Dedicated Pods
Product | OXVA Introduces XLIM PRO 4 With Liquid-Level Anti-Burn Technology and Dedicated Pods
Vaping brand OXVA introduced the XLIM PRO 4 refillable pod system in October 2026, featuring Anti-Burn Tech (ABT) based on smart e-liquid-level detection. The system can issue refill alerts and stop power output when e-liquid levels become too low. ABT requires the XLIM PRO 4 device and a dedicated XLIM ABT cartridge. Standard XLIM pods remain compatible but do not support ABT protection. OXVA previously introduced temperature-based anti-burn technology in the XLIM Pro 2 DNA, developed with Evolv. The new device features a 1,800mAh battery, 5–30W output and a 0.98-inch HD color screen. OXVA's official store lists the device at $37.90 and dedicated ABT replacement cartridges at $12.99. Independent testing confirmed the low-liquid protection response but recorded varying cartridge lifespans.
product
Oct.30
Indiana Halts Sales of Elf Bar, Lost Mary, MR FOG and iJOY Vapes Under Foreign-Adversary Rules; Some Products Return After Compliance Filings
Indiana Halts Sales of Elf Bar, Lost Mary, MR FOG and iJOY Vapes Under Foreign-Adversary Rules; Some Products Return After Compliance Filings
Indiana's Alcohol and Tobacco Commission (ATC) ordered tobacco certificate holders in September to remove certain vaping products marketed under Elf Bar, Lost Mary, MR FOG, iJOY and other brands from inventory under the state's foreign-adversary product law. The agency later listed 257 MR FOG products and 77 Lost Mary product entries as lawful for sale. The Lost Mary revision expressly stated that compliance evidence had been received for 20 additional products. 2Firsts compliance expert Kurt said potential filings could include e-liquid and ingredient-origin records, U.S. nicotine-analog supply-chain documentation and FDA premarket application status.
Regulations
Oct.08
Ispire Q4 Revenue Rebounds 33% but Full-Year Sales Still Fall 25% as FY2027 Focus Shifts to Malaysia Manufacturing, ODM, Nicotine Pouches and Age Verification
Ispire Q4 Revenue Rebounds 33% but Full-Year Sales Still Fall 25% as FY2027 Focus Shifts to Malaysia Manufacturing, ODM, Nicotine Pouches and Age Verification
Ispire Technology reported FY2026 revenue of about $96 million, down 24.7% year over year, as U.S. cannabis-vapor hardware and European e-cigarette sales declined by $17.4 million and $12.7 million, respectively. Fourth-quarter revenue rose 32.5% to $26.7 million, while quarterly gross margin fell to 6.3%. For FY2027, the company is prioritizing Malaysia manufacturing and vapor ODM while continuing to develop nicotine pouches, IKE Tech age-verification technology and G-Mesh licensing. Ispire has not separately disclosed the revenue or profit contribution of those newer businesses.
Regulations
Sep.17 by 2Firsts Perspectives
U.S. Rep. Krishnamoorthi Questions FDA Over Planned PMTA Rewrite, Seeks Communications With Altria and Reynolds
U.S. Rep. Krishnamoorthi Questions FDA Over Planned PMTA Rewrite, Seeks Communications With Altria and Reynolds
U.S. Rep. Raja Krishnamoorthi on Oct. 6 questioned the FDA over its plan to reassess and potentially replace the 2021 PMTA regulatory framework, asking the agency to identify provisions it may change or eliminate, state whether current scientific evidentiary standards will be maintained, and disclose communications with Altria, Reynolds and other parties challenging the rule. Krishnamoorthi led a congressional investigation into JUUL and youth vaping in 2019 and has since remained active on e-cigarette regulation and enforcement.
Regulations
Oct.08