Fourth-generation Vaping Devices Increase Risk to Immune Cells

Innovation by UNC HEALTH
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

 

UK Peer Seeks to Weaken “Generational Smoking Ban” – Report Reveals Discussions with BAT Executive Relative
UK Peer Seeks to Weaken “Generational Smoking Ban” – Report Reveals Discussions with BAT Executive Relative
Lord Strathcarron, a member of the UK House of Lords, has admitted to discussing the government’s Tobacco and Vapes Bill with a relative who holds a senior role at British American Tobacco (BAT). He is advocating amendments to scrap the bill’s core “generational smoking ban” provision, raising questions of potential conflict of interest.
Oct.27
2Firsts Exclusive | AVM President Allison Boughner: The U.S. Vape Market Reshapes Under a Regulatory Storm
2Firsts Exclusive | AVM President Allison Boughner: The U.S. Vape Market Reshapes Under a Regulatory Storm
Amid intensified regulation and sweeping market shifts, the U.S. vaping industry is undergoing a profound transformation. In an exclusive interview with 2Firsts, AVM President Allison Boughner discusses how enforcement is reshaping brands, distribution, products, compliance, and U.S.-based manufacturing.
Oct.20
Altria Q3 2025 Earnings Report: Net Revenue of $6.072 Billion and Launch of on!PLUS in the U.S.
Altria Q3 2025 Earnings Report: Net Revenue of $6.072 Billion and Launch of on!PLUS in the U.S.
Altria reported Q3 2025 net revenue of $6.072 billion, a 3.0% year-on-year decline. Adjusted EPS increased 3.6% to $1.45. The company expanded its share repurchase program to $2 billion and launched the on!PLUS nicotine pouch in Florida, North Carolina, and Texas.
Oct.31 by 2FIRSTS.ai
XQS Rolls Out Two Beverage-Flavoured Nicotine Pouches in UK; Says Convenience Stores Are the Fastest-Growing Channel
XQS Rolls Out Two Beverage-Flavoured Nicotine Pouches in UK; Says Convenience Stores Are the Fastest-Growing Channel
Scandinavian Tobacco Group (STG) UK has added two beverage-inspired variants—Cola Lime and Fizzy Peach—to its XQS nicotine pouch range. Both come in an 8mg strength and are available exclusively via the Vape Supplier website, with a recommended retail price of £5.50.
Oct.29 by 2FIRSTS.ai
Irish Cabinet to Consider Bill Banning Sale of Single-Use Vapes
Irish Cabinet to Consider Bill Banning Sale of Single-Use Vapes
Ireland’s Minister for Health, Jennifer Carroll MacNeill, will seek Cabinet approval today for the publication of the Public Health (Single-Use Vapes) Bill 2025, which proposes banning the retail sale of single-use or disposable vapes six months after becoming law. The measure aims to address the growing use of disposable vapes, particularly among young people, and close regulatory gaps around emerging nicotine products such as pouches.
Nov.18 by 2FIRSTS.ai
Philip Morris and R.J. Reynolds Face Trial Over Woman’s Lung Cancer Death in Massachusetts
Philip Morris and R.J. Reynolds Face Trial Over Woman’s Lung Cancer Death in Massachusetts
According to Law360, the family of Maria Petruzziello has taken Philip Morris and R.J. Reynolds to trial in Massachusetts, alleging the companies are responsible for her 2019 lung cancer death after decades of smoking. Plaintiffs argue her experience mirrors many smokers, while the defense points to her years-long cessation and personal choice.
Dec.03 by 2FIRSTS.ai