E-cigarette and vaping associated lung injury (EVALI) emerged in 2019. Since then, researchers have been investigating the biophysical impact of the additives used in these devices. In this study, the group exclusively focused on vitamin E acetate (VEA), which has been linked to lung damage in cannabis-based vape users.
Although VEA has since largely been banned for consumption by inhalation, it may still be present in the inhaled vapours after being used to dilute other ingredients. As the industry has rapidly grown, the range of additives and diluents in inhaled vapours has been challenging to regulate. This has allowed widespread exposure to possible toxins without scientists having any insight into their long-term effects on the lungs.
As well as this, the molecular-scale intricacies of the breathing process are still quite poorly defined. With the prevalence of inhaled toxins, small molecules, and viruses, it is important to explore these fundamental interactions to understand the origin of respiratory illnesses and to discover new interventions.
Using VEA as a case study, the group used neutron reflectometry on the Inter beamline at ISIS, and small angle neutron scattering and neutron spin echo at ORNL to study its interaction with a model pulmonary surfactant membrane, like those found in the lungs.
“Neutron reflectometry is one of the few techniques that is able to probe soft matter monolayers at sub-molecular resolutions," explains the study's corresponding author, Drew Marquardt from the University of Windsor. “The Inter reflectometer provided us with a world-class instrument to measure these monolayer structures across a broad length scale with high-resolution, all under biologically relevant conditions."
This technique gave them an insight into the monolayer structure of their model system, and they found that the VEA does not disrupt monolayer structure significantly. These results led them to determine that the mechanism of action lies in the mechanical/dynamic properties of the pulmonary surfactant.
“This work is an excellent example of the importance of appreciating dynamics as a critical aspect of the structure of soft materials," adds Drew. “Neutrons are possibly the only interrogation method that allows researchers to measure the dynamics of membranes in their native aqueous environment."
The group's findings provide a foundation for the respiratory toxicity of VEA but also show the significance of the composition of the lipids in the membrane on the fundamental biophysics of breathing. Their results can be used to understand other respiratory irritants and illnesses in the future.
They also saw that VEA has a different effect on the membrane models than naturally occurring vitamin E. This raises caution in grouping vaping additives together in their pharmacological effects. With this, they hope to encourage specific toxicological assessments for all e-cigarette/vaping ingredients, not just the active component.
This project represents a long-time collaboration between Mario Campana, a beamline scientist at ISIS, Piotr Zolnierczuk and Venkatesh Pingali from Oak Ridge National Lab, Elizabeth Kelley, Michihiro Nagao from the NIST Center for Neutron Research and three Canadian research institutions (the University of Windsor, Brock University and the Canadian Centre for Alternatives to Animal Methods).
“Each party contributed expertise in neutron scattering, biophysics, biology, and chemistry to bring this multidimensional project to life," explains Drew. “Mario Campana from ISIS was a great help from setting up the sample environment through to data analysis. This was our research group's first neutron reflectometry experiment and first experiment at ISIS, and Mario helped to lower the entry barrier to the technique. We are very grateful for his support."
In the future, they aim to characterise models for respiratory biophysics that are even more lifelike and use them to understand increasingly complex respiratory illnesses. They also plan to investigate the structure and dynamics of the membrane assemblies that form in the lungs during breathing.
Further information:
The full paper can be found at DOI: 10.1021/acs.chemrestox.4c00425
The work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC).
