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

 

Russia’s Vape Device Labeling Regime Enters Force: Registration Starts in September, Mandatory Coding in December
Russia’s Vape Device Labeling Regime Enters Force: Registration Starts in September, Mandatory Coding in December
Russia's digital labeling regime for reusable e-cigarettes and similar personal vaping devices entered its first mandatory phase in September 2026. From September 1, manufacturers, importers and other market participants must register with the national Chestny ZNAK tracking system. From December 1, newly manufactured and imported covered devices will be required to carry digital identification codes and be reported as entering circulation. Russia has also issued new operational guidance for imports, marking the transition from a voluntary pilot to phased mandatory implementation.
Sep.15
China Tobacco Plans CNY 60 Billion Investment in ICBC, Agricultural Bank as Strategic Ties Extend Beyond Equity
China Tobacco Plans CNY 60 Billion Investment in ICBC, Agricultural Bank as Strategic Ties Extend Beyond Equity
China National Tobacco Corporation and several subsidiaries plan to invest a combined CNY 60 billion ($8.7 billion) in share placements by Industrial and Commercial Bank of China and Agricultural Bank of China as strategic investors. The agreements extend beyond equity investment to corporate governance, banking services and supply-chain finance. The filings also disclose 2025 data on China Tobacco’s tax and profit contributions and industry scale.
Sep.07
Global Nicotine-Pouch E-Commerce Group Haypp Shuts Sweden’s Snusnetto Over Age Verification as Identity Checks Become Industry Infrastructure for New Nicotine Products
Global Nicotine-Pouch E-Commerce Group Haypp Shuts Sweden’s Snusnetto Over Age Verification as Identity Checks Become Industry Infrastructure for New Nicotine Products
Sweden's Supreme Administrative Court has declined to hear an appeal over age verification for tobacco and nicotine products collected from parcel lockers, leaving in place a lower-court ruling that geo-located BankID verification is insufficient to securely verify the actual recipient. Haypp Group has stopped tobacco and nicotine sales through Snusnetto and is deploying a new system across its other Swedish e-commerce sites to verify the age of the person who actually opens the locker and receives the shipment. The change comes as age verification across next-generation nicotine products expands from purchase checks into retail, delivery and, for some e-cigarettes, device access itself.
Regulations
Oct.20
U.S. Expands Illicit Vape Enforcement as ATF Brings PACT Act Powers Into Trade Fraud Task Force
U.S. Expands Illicit Vape Enforcement as ATF Brings PACT Act Powers Into Trade Fraud Task Force
The U.S. Bureau of Alcohol, Tobacco, Firearms and Explosives said on September 23 that it has joined the interagency Trade Fraud Task Force to strengthen enforcement against illegal, misdeclared and smuggled vape and tobacco products. ATF will bring its authority under the Prevent All Cigarette Trafficking Act into the task force, including registration, reporting, shipping and record-inspection requirements covering interstate sales of electronic nicotine delivery systems. ATF said the move will strengthen its ability to trace illicit products from U.S. points of entry through domestic trafficking and distribution networks.
News
Sep.28 by 2Firsts Perspectives
Ispire Q4 Revenue Rebounds 33% but Full-Year Sales Still Fall 25% as FY2027 Focus Shifts to Malaysia Manufacturing, ODM, Nicotine Pouches and Age Verification
Ispire Q4 Revenue Rebounds 33% but Full-Year Sales Still Fall 25% as FY2027 Focus Shifts to Malaysia Manufacturing, ODM, Nicotine Pouches and Age Verification
Ispire Technology reported FY2026 revenue of about $96 million, down 24.7% year over year, as U.S. cannabis-vapor hardware and European e-cigarette sales declined by $17.4 million and $12.7 million, respectively. Fourth-quarter revenue rose 32.5% to $26.7 million, while quarterly gross margin fell to 6.3%. For FY2027, the company is prioritizing Malaysia manufacturing and vapor ODM while continuing to develop nicotine pouches, IKE Tech age-verification technology and G-Mesh licensing. Ispire has not separately disclosed the revenue or profit contribution of those newer businesses.
Regulations
Sep.17 by 2Firsts Perspectives
South Korea Imports 12,126 Kg of Nicotine Analogues From April to August After Bringing Synthetic Nicotine Under Tobacco Law
South Korea Imports 12,126 Kg of Nicotine Analogues From April to August After Bringing Synthetic Nicotine Under Tobacco Law
South Korea's liquid-vape market is showing changes across raw-material imports, product types and sales channels after synthetic nicotine came under the Tobacco Business Act on April 24. Customs data show nicotine-analogue imports totaled 12,126 kilograms from April through August, while synthetic-nicotine imports over the same five months totaled 231,663 kilograms, just 39.3% of the amount imported in March alone. Physical liquid-vape stores tracked in Seoul and Gyeonggi Province fell 9.9%, unmanned outlets edged higher and online sales listings increased from 27,774 to 42,437. Government testing of 105 liquid inhalation products promoted as nicotine-free separately found nicotine in 13 and 6-methylnicotine in 12.
Sep.22