Cherry vape flavor compromises lab model of lung’s slippery coating

In late 2019, as the US saw a surge of vaping-related lung injuries, the Centers for Disease Control and Prevention warned against e-cigarette use. Despite the warning, e-cigarette sales have continued to rise and vape consumers can now choose from more than 6,000 vape products and 16,000 unique flavored e-liquids.

Earlier this month, chemists reported a new mechanism for how vape flavors can harm lungs. In experimental and computational models, the e-liquid cherry flavoring, benzaldehyde, and a derivative of it formed in vapes impair the coating found inside lungs (Environ. Sci. Technol. 2024, DOI: 10.1021/acs.est.3c07874).

The models indicate that the two compounds insert themselves into the lung surfactant, a delicate, slick monolayer of mostly phospholipids and some proteins. Once there, the flavor molecules cozy up to surfactant proteins and make the lung’s coating less responsive.

“Surfactant is the lubricant that allows you to breathe,” says study author Jorge Bernardino de la Serna at Imperial College London. Without surfactant, the inner surfaces of lungs’ air sacs would stick to each other when deflated, preventing proper inhalation.

Benzaldehyde is in 75% of e-liquids. The heat provided by a vape accelerates benzaldehyde’s reaction with propylene glycol, a main ingredient in most e-liquids, to form benzaldehyde propylene glycol acetal (BPGA), Bernardino de la Serna says. The researchers wanted to investigate BPGA because it’s a known respiratory irritant and because it’s hydrophobic, similar to the lipids in the surfactant layer.

So they put calf lung surfactant—used to help babies who can’t re-expand their lungs after their initial breaths—on instruments called surfactometers to measure how well the surfactant behaved when exposed to benzaldehyde and BPGA. The group saw surface tension increase and compressibility decrease in the presence of each molecule, suggesting that they make the breathing cycle more difficult.

Their experiments suggested that benzaldehyde and BPGA interfere with the surfactant layer mainly by getting close to two hydrophobic proteins. Molecular dynamic simulations agreed. BPGA, in particular, sneaks right inside the surfactant monolayer and packs itself around the proteins, preventing the surrounding phospholipids from tightly packing together and tilting as they do in functioning lungs.

Discovery of the new mechanism, the researchers say, highlights the “widely unconsidered” potential danger of using food flavorings in e-cigarette vapor, which is not eaten, but inhaled. And benzaldehyde is just one of many aldehyde vape flavorings, Bernardino de la Serna adds. Others, like vanillin and cinnamaldehyde, likely also form acetals that interact with surfactant.

His group further found that, after about 40 cycles, lung surfactant eventually squeezes the irritants down. The group is now following the irritants’ path to the alveolar cells below and investigating a possible cellular effect.

Ruud Veldhuizen, an expert in pulmonary surfactant at Lawson Health Research Institute, said that the surfactant impairment is “very convincing.” People who vape, he added, could have a weakened surfactant system making their lungs more susceptible to disease.