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

 

PMI's IQOS Extends ZAMNA Electronic-Music Partnership to Spain as Vogue España Publishes Branded Content
PMI's IQOS Extends ZAMNA Electronic-Music Partnership to Spain as Vogue España Publishes Branded Content
Philip Morris International's IQOS has extended its partnership with electronic-music event brand ZAMNA to Spain, setting up a House of IQOS at ZAMNA Madrid. Vogue España and Time Out Madrid subsequently published branded content clearly labeled as collaborations with IQOS. PMI has also expanded its company-owned IQOS boutique network in Spain to seven cities this year. The company says IQOS's adjusted heated-tobacco market share in Europe reached 12.6% in the first quarter of 2026, with Spain among its stronger-performing European markets.
Sep.20
Inside Nicotine-Pouch M&A Through Imperial's Yoik Deal: Latham, KPMG, PwC, Goldman Sachs and Morgan Stanley Form the Adviser Lineup
Inside Nicotine-Pouch M&A Through Imperial's Yoik Deal: Latham, KPMG, PwC, Goldman Sachs and Morgan Stanley Form the Adviser Lineup
Imperial Brands' acquisition of Swedish Helwit owner Yoik Group AB has highlighted the professional-services firms supporting cross-border oral nicotine M&A. Latham & Watkins and KPMG advised Imperial, while PwC and TM & Partners advised Yoik. KPMG also appeared on Imperial's acquisition of Black Buffalo earlier in 2026, while PwC played an extensive role in KT&G's acquisition of Swedish nicotine-pouch company Another Snus Factory. Imperial's public disclosures put the global modern oral nicotine delivery market at approximately £8.8 billion in retail sales and 23.5 billion pouches in 2024
Sep.20
IQOS Enters Kantar BrandZ Global Top 100 for First Time, Valued at $36.6 Billion and Ranked No. 74
IQOS Enters Kantar BrandZ Global Top 100 for First Time, Valued at $36.6 Billion and Ranked No. 74
Philip Morris International’s IQOS has entered the Kantar BrandZ Top 100 Most Valuable Global Brands for the first time, ranking No. 74 with a brand value of $36.634 billion and becoming one of only three newcomers to the 2026 ranking. Kantar said the combined value of the Global Top 100 reached $13.1 trillion, up 22% year on year, while the threshold for entry rose to a record high. PMI says IQOS has more than 35 million users worldwide and surpassed $10 billion in annual net revenues within a decade of launch.
Sep.03
UK Vape Maker Riot Enters Clacton By-Election to Fight Government 'White Packaging' Proposals
UK Vape Maker Riot Enters Clacton By-Election to Fight Government 'White Packaging' Proposals
British e-liquid manufacturer Riot Labs has introduced a fictional “candidate” called Riot Man around the Clacton parliamentary by-election, seeking to mobilize consumers and retailers against parts of the UK government’s proposed restrictions on vape packaging, device appearance and retail displays. Riot Man is not listed as an official candidate.
Aug.12
STIIIZY Redesign Fails to Escape PAX Labs Patent Import Ban as Section 337 Case Also Involves China ALD
STIIIZY Redesign Fails to Escape PAX Labs Patent Import Ban as Section 337 Case Also Involves China ALD
U.S. Customs and Border Protection ruled that STIIIZY had not shown that the redesigned cannabis-vape products covered by its latest request fall outside an ITC limited exclusion order tied to PAX Labs patents. CBP accepted some of STIIIZY’s claim-construction and non-infringement arguments, but the company did not address two additional claims in the same patent. Earlier STIIIZY redesigned cartridges and certain associated components imported with them had received separate CBP clearance.
Sep.16
RLX Technology Dropped From FTSE All-World as International Business Reaches 68.5% of Q2 Revenue
RLX Technology Dropped From FTSE All-World as International Business Reaches 68.5% of Q2 Revenue
RLX Technology (NYSE: RLX) has been removed from the FTSE All-World Index, effective September 21. FTSE Russell records show RLX was already part of its global equity index universe by 2022, when its American depositary receipts were classified as China Large Cap securities. Trading volume rose to about 44.77 million shares on September 18, roughly 23 times the previous session's volume. RLX reported RMB1.0105 billion in second-quarter revenue, up 14.8% year over year, with international operations contributing 68.5%. The company also acquired a 51% stake in one of Western Europe's largest distributors of next-generation smoke-free and FMCG products in July.
Sep.22