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 Nicotine Salts to Cocrystals: China’s Shenzhen Huabao institute explores a more stable form for sustained nicotine release
From Nicotine Salts to Cocrystals: China’s Shenzhen Huabao institute explores a more stable form for sustained nicotine release
China-based Shenzhen Huabao Collaborative Innovation Technology Research Institute Co., Ltd. has filed a patent application for a nicotine-ascorbic acid cocrystal, exploring a new solid-state form of nicotine. The patent proposes applications across e-liquids, heated tobacco sticks, oral tobacco, chewing tobacco and snuff. In nicotine pouch tests disclosed in the filing, cocrystal formulations showed less than a 6% decline in nicotine content after three months of accelerated storage and a release profile combining early-stage release with sustained delivery over 60 minutes. The filing reflects exploration of nicotine forms beyond conventional nicotine base and nicotine salts.
Aug.13
Former Roche Neuroscience and Rare Diseases Communications Director Ria Kioupritzi Joins PMI as Scientific Affairs Director
Former Roche Neuroscience and Rare Diseases Communications Director Ria Kioupritzi Joins PMI as Scientific Affairs Director
Eleftheria (Ria) Kioupritzi, a biopharmaceutical professional with more than 15 years of experience, has joined Philip Morris International as Director Scientific Affairs within Corporate Affairs. She previously served at Roche as Senior Scientific Communications Director for Neuroscience and Rare Diseases and worked extensively in spinal muscular atrophy. Her earlier career also covered competitive intelligence, clinical and regulatory monitoring, pipeline development and launch preparation. During her time working in Roche's SMA field, Evrysdi passed through several U.S. FDA milestones, including its initial approval, an expanded indication for younger infants and approval of a tablet formulation. Public records do not show that Kioupritzi herself led the FDA submissions.
Sep.22
Product | JTI Launches Ploom AURA Teal Electric Pop in South Korea, Its First Dual-Color Edition
Product | JTI Launches Ploom AURA Teal Electric Pop in South Korea, Its First Dual-Color Edition
JTI Korea launched the Ploom AURA Teal Electric Pop limited edition in South Korea on September 1, 2026, marking the first dual-color design in the Ploom AURA range. The device combines a dark green body with teal accents and is accompanied by matching Front Panel, Back Cover and Pocket Bag accessories. The standalone device is priced at KRW 29,000, with three additional device-and-accessory bundles available. The release continues JTI Korea's use of limited colorways and interchangeable accessories to expand the Ploom AURA portfolio without introducing a new hardware platform.
Sep.03
Australia’s Victoria Steps Up Illegal Tobacco Enforcement With Store Closures and Penalties of Up to A$2.5 Million
Australia’s Victoria Steps Up Illegal Tobacco Enforcement With Store Closures and Penalties of Up to A$2.5 Million
Australia’s state of Victoria has activated new powers allowing Tobacco Licensing Victoria and police to shut premises suspected of selling, supplying or possessing illicit tobacco for up to 90 days. Longer closures can be ordered by a magistrates’ court. Businesses subject to closure orders must generally cease all trading and will be placed on a public list. Breaching a closure order can carry penalties of up to A$2.5 million and 20 years in prison.
Sep.10
UK HMRC Unveils Red and Yellow Transitional Vape Duty Stamps Ahead of October Tax Launch
UK HMRC Unveils Red and Yellow Transitional Vape Duty Stamps Ahead of October Tax Launch
HM Revenue & Customs (HMRC) has released sample images of the UK’s transitional vaping duty stamps, showing red and yellow versions ahead of the new Vaping Products Duty and Vaping Duty Stamps Scheme starting on October 1, 2026. Transitional stamps contain physical security features but no digital scanning function. Approved businesses may purchase them through November 30 and affix them through December 31. HMRC has not stated that the red and yellow samples represent different product categories or tax statuses.
Regulations
Sep.02
PMI Expands U.S. ZYN Portfolio With New 1.5 mg and 8 mg Strengths, Moves Toward a Unified 20-Pouch-Per-Can Format
PMI Expands U.S. ZYN Portfolio With New 1.5 mg and 8 mg Strengths, Moves Toward a Unified 20-Pouch-Per-Can Format
Philip Morris International is expanding its U.S. ZYN nicotine pouch portfolio with new 1.5 mg and 8 mg strengths and plans to move its core 3 mg and 6 mg dry-pouch products from 15 to 20 pouches per can in the fourth quarter of 2026. ZYN ULTRA is also commercially available, with FDA authorization covering 10 products at 9 mg and one 11 mg Smooth product. PMI U.S. lists the new 1.5 mg and 8 mg strengths as commercially available, but as of September 10 they do not appear on the FDA’s public authorization list. Public materials do not identify which PMTA submissions cover the two new strengths or their current review status.
Sep.11