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

 

Product | Four CrossBar 20K 13mL High-Puff Vapes Listed on Pennsylvania's ENDS Directory, Rated for Up to 20,000 Puffs
Product | Four CrossBar 20K 13mL High-Puff Vapes Listed on Pennsylvania's ENDS Directory, Rated for Up to 20,000 Puffs
Four CrossBar 20K disposable e-cigarettes appeared on Pennsylvania's 163-entry ENDS directory ahead of enforcement beginning October 19, 2026. The devices feature 13mL e-liquid reservoirs, 50mg/mL nicotine, 2,000mAh batteries and 0.9Ω mesh coils, with advertised puff counts of up to 20,000. CrossBar was the only modern high-puff disposable series among the directory's 15 disposable entries. Its packaging emphasizes New York design and Japanese-origin flavoring, while historical CrossBar records identify a registered U.S. tobacco manufacturing-related establishment. The link between the newer 13mL devices and earlier 1.3mL PMTA filings remains unconfirmed.
product
Oct.26
Altria’s USSTC Starts $250 Million Kentucky Expansion, Adding More Than 200 Jobs
Altria’s USSTC Starts $250 Million Kentucky Expansion, Adding More Than 200 Jobs
U.S. Smokeless Tobacco Company, an Altria Group company, has broken ground on an approximately $250 million manufacturing expansion in Hopkinsville, Kentucky. The roughly 270,000-square-foot facility is expected to create more than 200 jobs and absorb processing, manufacturing and packaging operations currently split between Hopkinsville and Nashville, Tennessee. USSTC previously said production at its Nashville facility is expected to wind down by early 2028. The project forms part of Altria’s broader effort to modernize and consolidate its U.S. smokeless tobacco manufacturing network.
Sep.10
North Carolina Tightens Vape Product Directory Enforcement, Expands State and Local Powers as Violators Face Fines, Product Seizures and License Suspension or Revocation
North Carolina Tightens Vape Product Directory Enforcement, Expands State and Local Powers as Violators Face Fines, Product Seizures and License Suspension or Revocation
North Carolina has expanded enforcement of its vapor product directory rules, authorizing more state and local law enforcement participation and establishing a task force led by the State Bureau of Investigation. The legislation requires at least one unannounced compliance inspection annually for retailers, distributors and wholesalers handling covered products. Penalties effective October 1, 2026, include civil fines of $500–$750 for a first violation and $1,000–$1,500 for repeated violations within 12 months, along with potential license suspension or revocation. Manufacturers may face penalties of $10,000 per unlisted product. The measures strengthen the product directory system established in 2024.
Regulations
Oct.28
Product | R.J. Reynolds Launches Four Flavored Vuse Pro Pods for Vuse Alto Devices in U.S.
Product | R.J. Reynolds Launches Four Flavored Vuse Pro Pods for Vuse Alto Devices in U.S.
R.J. Reynolds Vapor Company has introduced Vuse Pro prefilled pods in Peach, Berry, Watermelon and Fresh Mint in selected U.S. states. Vuse’s U.S. website says the pods are intended for use with existing Vuse Alto devices. Each contains 2.0 mL of e-liquid at 5.0% nicotine by weight, uses nicotine salts and is offered in two- and four-pod packs. Reynolds said the rollout includes mandatory ID scanning for every purchase, purchase limits, stronger retailer-accountability requirements and strict age-restricted marketing standards. The four pods have not received marketing authorization from the U.S. Food and Drug Administration.
Sep.10
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
JTI Proposes 25-Cent Irish Cigarette Tax Increase, Says It Could Raise €45 Million
JTI Proposes 25-Cent Irish Cigarette Tax Increase, Says It Could Raise €45 Million
Japan Tobacco International's Irish business has proposed a €0.25 tax increase on a pack of 20 cigarettes in its pre-Budget 2027 submission, below the €0.50-or-more increases typically imposed in recent Irish budgets. JTI says the proposal could generate around €45 million in additional Exchequer revenue while limiting further movement toward illicit and non-Irish-tax-paid tobacco. Revenue's existing estimate for a comparable €0.25 increase, including pro-rata rises on other tobacco products, is about €18 million for a full year.
JTI
Sep.18 by 2Firsts Perspectives