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

 

U.S. Customs Plan to Require Foreign Export Declarations Could Deal ‘Devastating’ Blow to China’s Vape Exports, Logistics gl Expert Says
U.S. Customs Plan to Require Foreign Export Declarations Could Deal ‘Devastating’ Blow to China’s Vape Exports, Logistics gl Expert Says
A U.S. Customs and Border Protection proposal to collect foreign export declarations and other overseas customs documents could expose discrepancies in the value, classification and description of China-made vape shipments entering the United States. A veteran Chinese logistics professional told 2Firsts that the measure, if implemented, could undermine the all-inclusive shipping model used by some unauthorized vape exporters and push parts of the trade toward costlier underground channels. The risk extends beyond higher duties: accurately declared products may also be more readily identified as unauthorized e-cigarettes subject to FDA enforcement.
Special Report
Sep.07
Smoore Seeks to Toss CCELL Price-Fixing Claim as Court Weighs Vertical Distribution Versus Horizontal Conspiracy
Smoore Seeks to Toss CCELL Price-Fixing Claim as Court Weighs Vertical Distribution Versus Horizontal Conspiracy
Smoore and four authorized U.S. CCELL distributors are asking a California federal court to permanently dismiss a core antitrust claim brought by direct purchasers. Plaintiffs allege that Smoore coordinated minimum wholesale prices, customer allocation and limits on price competition among distributors, amounting to a per se unlawful horizontal conspiracy. The defendants say the alleged conduct reflects ordinary vertical relationships between a manufacturer and its distributors. The court previously dismissed a similar claim, and the latest dispute centers on whether the second amended complaint adds sufficient facts to establish a horizontal agreement.
Sep.14
Why AIRSCREAM Built its European Production Hub for Regulated Market Growth
Why AIRSCREAM Built its European Production Hub for Regulated Market Growth
AIRSCREAM’s production hub in the Czech Republic brings nicotine pouch manufacturing, e-liquid bottling, product documentation, warehousing and international logistics into one operation, giving brands and commercial partners a practical platform from which to launch, expand and enter new markets.
Market
Sep.16 by 2Firsts Perspectives
Product | PMI Launches Airport-Exclusive IQOS Skylens Limited Edition, Expanding From Japan’s Narita to Travel Retail Markets in 13 Countries Summary
Product | PMI Launches Airport-Exclusive IQOS Skylens Limited Edition, Expanding From Japan’s Narita to Travel Retail Markets in 13 Countries Summary
Philip Morris International (PMI) has introduced the airport-exclusive limited-edition IQOS ILUMA i PRIME Skylens, the company’s first device created specifically for airport travel retail. Inspired by the world of flight and finished in metallic blue, Skylens debuted at Narita International Airport in Japan before expanding into selected airport duty-free and travel-retail channels across 13 countries in Europe, Asia, the Middle East and Africa. The product retains the existing IQOS ILUMA i PRIME platform, with differentiation centered on airport exclusivity, design and travel-retail execution rather than a new heating architecture.
PMI
Aug.19
2Firsts Hosts China Market Forum at InterTabac as Global Industry Attention to China’s Tobacco Sector Deepens
2Firsts Hosts China Market Forum at InterTabac as Global Industry Attention to China’s Tobacco Sector Deepens
On September 16, 2Firsts hosted a China-focused industry forum during InterTabac in Dortmund, bringing together more than 30 participants from North America, Europe, India, South Korea and other markets. The session covered traditional tobacco, next-generation products, exports, technology, regulation and supply chains, while examining how China’s tobacco sector operates, where its transformation may be heading, and why its growing role matters increasingly to companies across the global tobacco and nicotine industry.
Sep.21
R.J. Reynolds Vapor Company Launches Flavored Vuse Pro Pods in U.S. Without FDA Marketing Authorization
R.J. Reynolds Vapor Company Launches Flavored Vuse Pro Pods in U.S. Without FDA Marketing Authorization
R.J. Reynolds Vapor Company has begun selling four flavored Vuse Pro pods — Peach, Berry, Watermelon and Fresh Mint — in Ohio and selected other U.S. markets. According to the Vuse U.S. FAQ, Vuse Pro contains approximately 5.0% nicotine by weight, and Vuse Pro pre-filled pods are intended for use with Vuse Alto devices. Reynolds told 2Firsts that product labeling lists an e-liquid capacity of 2.0 mL per pod. The Vuse Alto Power Unit received FDA marketing authorization in 2024, while the new Vuse Pro pods themselves have not received marketing granted orders. The rollout follows the FDA’s May 2026 revision of enforcement priorities for certain unauthorized vaping products with qualifying pending applications.
BAT
Sep.10