Daily use of pod-based e-cigarettes alters the inflammatory state of multiple organ systems, including the brain, heart, lungs and colon, researchers at UC San Diego School of Medicine report. Effects also vary by e-cigarette flavor and can affect how the organ responds to infections, such as SARS-CoV-2.

The study, published April 12, 2022 in the journal eLife, is the first to evaluate the JUUL device and its flavoring agents in a multi-organ manner.

"These pod-based e-cigarettes have only become popular in the past five years or so, so we know very little about their long-term health effects," said senior study author Laura Crotty Alexander, M.D. Crotty Alexander) said. Chief of the Division of Pulmonary Intensive Care at the UC San Diego School of Medicine and Veterans Affairs San Diego Health Care System.

More than 12 million adults in the U.S. currently use e-cigarettes, with 18-24-year-olds having the highest use rates. Despite the popularity of e-cigarettes, research on e-cigarettes has been largely limited to short-term use, older devices (such as e-cigarette pens or box mods), and e-cigarettes with significantly lower nicotine concentrations than modern rechargeable pod systems Research on smoke oil.

Crotty Alexander's team focuses on the most well-known e-cigarette brand today, JUUL and its most popular flavors: mint and mango. To simulate chronic e-cigarette use, young adult mice were exposed to flavored JUUL aerosols three times a day for three months. The researchers then looked for signs of inflammation throughout the body.

The authors saw the most dramatic effects in the brain, where several markers of inflammation were elevated. Additional changes in neuroinflammatory gene expression were found in the nucleus accumbens, a brain region critical for motivation and reward processing.

The findings raise significant concerns, they say, because neuroinflammation in the region is associated with anxiety, depression and addictive behaviors, which may further fuel substance use and addiction.

"Many JUUL users are teenagers or young adults whose brains are still developing, so given how this affects their mental health and behavior, it's pretty scary to understand what's going on in their brains," says Crotty Alexander.

Inflammatory gene expression was also increased in the colon, especially after one month of exposure to e-cigarettes, which may increase the risk of gastrointestinal disease. In contrast, the heart showed reduced levels of inflammatory markers. This immunosuppressed state may make heart tissue more susceptible to infection, the authors say.

While the lungs did not show signs of inflammation at the tissue level, many gene expression changes were observed in the samples, and further research is needed on the long-term effects of pod-based e-cigarettes on lung health.

The researchers also found that the inflammatory response in each organ varied depending on the JUUL flavor used. For example, the hearts of mice inhaled with peppermint aerosol were much more sensitive to the effects of bacterial pneumonia than in mice inhaled with mango aerosol.

"It was a real surprise for us," Crotty Alexander said. "This suggests to us that the flavor chemicals themselves are also causing pathological changes. If someone who regularly used mint-flavored JUUL e-cigarettes became infected with COVID-19, their bodies might respond differently to the infection."

Each organ has its own fine-tuned immune environment, so disrupting this balance through vaping could lead to many long-term health effects, the authors wrote.

"Obviously, every vaping device and flavor must be studied to determine how it affects whole-body health," Crotty Alexander said.