An insight into the mechanisms of pulmonary toxicity from vaping
Researchers from RCSI, University of Medicine and Health Sciences, demonstrate how vaping pyrolysis of vitamin E acetate releases pulmonary toxic ketene and other carcinogens.
An increased number of pulmonary injury cases following the use of e-cigarette/vaping products have been reported by the US Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). The cause of these vaping-associated injuries remains unidentified, although they appear to result in airway-centred chemical pneumonitis from inhaled toxic substances. Alterations in lipid homeostasis may also play a role in this disease process.
The presence of vitamin E acetate (VEA) was found in the lung fluid of the majority of patients in these cases, even though the action of VEA was not fully consistent with the types of injuries seen.
An alternative mechanism of injury involves the production of ketene, a highly toxic gas, due to the pyrolysis of VEA added to some vape mixtures, particularly those containing tetrahydrocannabinol (THC) and cannabidiol (CBD) oils. These mixtures are often used for recreational purposes and have been closely linked to the cases of pulmonary injury.
Vaping devices are crude mini-pyrolysis apparatus that are capable of causing uncontrollable changes to the chemical composition of a vaping mixture. In the study available here, Professor Donal O’Shea and Dr Dan Wu from the Department of Chemistry at RCSI, University of Medicine and Health Sciences, illustrate the potential of VEA to release ketene under pyrolysis conditions. Furthermore, they demonstrate how using one of these readily available, store-bought vaping devices can achieve such conditions.
The aryl acetate functional group present in VEA is sensitive to pyrolysis and the same functional group is present in phenyl acetate, which is known to liberate ketene under pyrolysis. Ketene has a very high pulmonary toxicity and can be lethal in larger concentrations.
The RCSI team provided evidence that ketene could be formed from VEA by successfully utilising a technique known as atmospheric pressure chemical ionization mass spectrometry (APCI-MS), alongside density functional theory (DFT) calculations.
They went on to investigate the effect of vaping on VEA. Using several methods, including trapping experiments, the team proved that the act of vaping VEA can produce ketene.
This raises many more questions beyond just the chemistry of VEA.
Firstly, the wide array of vaping devices with controllable heating potential available should raise concern.
The temperatures achieved by heating coils in these devices range from 80°C to approximately 1000°C. A wide temperature range brings a wide variety of potential chemical reactions with unknown medical consequences. The materials in the heating coils and the coating on the coils may also act as catalysts for some of the chemical reactions taking place.
Complicating matters even further is the wide range of flavours available to be added to vaping mixtures at varying concentrations. Little is known about what end products are generated when these additives are heated to a range of temperatures.
Because of the limited regulation on materials used to produce vaping devices, the heating coils used and the varying temperatures that can be achieved, the same vaping mixture loaded into two different devices could potentially produce different end-products after the mixture is heated.
Secondly, although there is limited control or regulation on the materials that are used in vaping devices or the ingredients that are inhaled, a larger public health issue is the lack of knowledge on the potential dangers of the products that are formed through these processes. This highlights flaws surrounding regulation and responsibility in the provision of reliable information on vaping devices.
In theory, people can vape almost anything they please when they own a user-filled tank vaping device. While the effects may not be immediately apparent, like those seen in the patients diagnosed with vaping-associated lung injury, it is important to question if we will see an increase in benign and malignant diseases of the airway and lungs in years to come in patients with long-term exposure to vaping.
There is no longitudinal data on the risks of vaping compared to cigarette smoking, a new and worrying trend is observable in the uptake of vaping in people who have never smoked, particularly teenagers. This may be due in part to the unfounded beliefs that vaping is safe.
There has been a lot of debate surrounding the type of regulation that should be imposed on vaping devices and mixtures. Opinions from major health organizations are conflicted, which is understandable given the current lack of knowledge about the safety of vaping and the concern about the dangers of traditional cigarette smoking.
As data on the effects of vaping are accumulated, it needs to be decided who is responsible for proving the safety or dangers of vaping.
For example, a pharmaceutical company that designs a new drug is responsible for bringing that new drug through multiple phases of clinical trials to determine its safety and efficacy; they must also follow it up for years after it’s been released onto the market to look for rare and delayed side-effects.
It has to be considered whether the companies who produce vaping mixtures and vaping devices should be subjected to the same rigorous rules and regulations with their products, or if it should be up to the scientific and medical community to slowly accumulate data and document the short and long-term effects, if any, from vaping many years from now.
For now, it looks likely that understanding the effects of vaping products will require a concerted effort from a wide array of scientists, including chemists, clinicians and public health specialists.
RCSI is already proving itself as an institution with a strong interest in vaping with another paper published last week by Dr Brendan McDonnell, available here, focusing on the birth weight of infants born to mothers who use e-cigarettes. More about our discoveries and research breakthroughs can be found here.
Journal Article Information:
Potential for release of pulmonary toxic ketene from vaping pyrolysis of vitamin E acetate.
PNAS March 24, 2020 117 (12) 6349–6355
https://doi.org/10.1073/pnas.1920925117
