It is possible that the TBI group itself differed in some way that we did not account for. A potential future prospective study could integrate more clinical information about a participant’s head injury such as the location of initial insult, Glasgow Coma Scale rating, or more precision on duration of unconsciousness. Future studies could also utilize functional magnetic resonance imaging information as another means to evaluate neuropsychological performance simultaneously with metabolic imaging. Looking at the number of head injuries that a person experienced could also have been worthwhile , as neuropsychological tests of memory, attention, and motor function have shown worse performance with repeated head injury . For example, HIV– individuals with multiple TBIs, when compared to those with a single TBI, exhibit significantly poorer memory and executive functioning . Given that these two neurocognitive domains are the same as those that showed significant deficits in our study, it would be interesting to determine whether there are cumulative effects of multiple TBI on HIV-associated neurocognitive decline. Despite some limitations, our study does indicate that TBI may increase vulnerability to brain dysfunction in HIV-infected individuals. If confirmed, the results indicate that those involved with HIV care need to take head injury into account in their neurological evaluation and clinical management of HIV patients.After the 2019–2020 outbreak of e-cigarette or vaping product use-associated lung injury in which the Centers for Disease Control and Prevention reported over 2,800 hospitalizations of patients displaying symptoms of acute respiratory distress,cannabis grow supplies serious public health concerns have been raised about the safety of e-cigarettes. In the initial investigations, evidence has supported that vaping of vitamin E acetate , a synthetic form of vitamin E that was used to “cut” or dilute black market or homemade tetrahydrocannabinol , was a major cause of the onset of EVALI symptoms.
Several different mechanisms of toxicity have been proposed since the outbreak, yet the exact causative agents and molecular mechanisms through which VEA vaping emissions resulted in lung toxicity are still not well understood. VE and VEA alone are considered safe for dermatological application in skin-care products and as well as for consumption in foods and dietary supplements. Several studies since the outbreak, however, have found that e-liquids like VEA undergo major thermal decomposition during the vaping process to form products that are often more toxic than the parent oil. VEA in particular has been found to decompose into a wide range of emission products including VE, alkenes such as 1-pristene, alcohol-containing compounds such as 3,7,11-trimethyl-1-dodecanol, durohydroquinone, and durohydroquinone monoacetate, and carbonyl-containing compounds such as ketene, 4-acetoxy-2,3,5-trimethyl-6-methylene-2,4-cyclohexadienone, and duroquinone. Still, the overall risk of exposure of each identified product to those who vaped VEA is unclear. For example, ketene gas has been hypothesized to form from the cleavage of the acetate group of VEA. However, this reaction has been calculated to only be feasible at temperatures exceeding 500˚C–temperatures that are likely to only occur under “dry puff” conditions. The operating temperature of the vape device is one of many parameters–including the model of e-cigarette used, puff duration, interval between puffs, etc.–that a user may alter to customize their vaping experience. A few studies to date have investigated the impact of increased temperature on the size and volume distribution of emitted vaping aerosols, reporting that greater coil temperatures result in larger puff volumes, but decrease the size of emitted particles. A recent study in 2021 found that the emission of volatile degradation products, including various carbonyl-containing species, was significantly enhanced when temperature was increased from 170 to 280˚C. In addition, increased coil temperature and characteristics of the vape device have also been found to influence other aspects of vaping emissions, such as the release of metals and the level of carbonyl-containing compounds or radical species.
E-cigarette atomizers and heating elements are often comprised of various transition metals including nickel, iron, and chromium which not only pose a risk of metal toxicity to vape users , but may play a role in the catalysis of thermal degradation of the e-liquid. One study by Saliba et al. found that e-cigarette filament wires had a significant impact on the production of carbonyl-containing compounds from propylene glycol vaping, lowering the temperature required to form carbonyl species by nearly 200˚C. However, the factors affecting the chemical composition of e-cigarette degradation products have yet to be fully characterized. The objective of this study was to examine the influence of variable temperature on the product distribution of e-cigarette vaping emissions, using VEA as a model e-liquid. To do so, we performed a non-targeted analysis of the aerosol-phase constituents at relevant, mid-range vaping temperatures using gas chromatography/mass spectrometry . We hypothesized that elevated temperature of the heating coil during vaping could enhance thermaldegradation of VEA, causing a shift in emission product distribution and toxicity in vapers. VEA vaping emissions were produced at coil temperatures ranging between 176 to 356˚C using a variable voltage vape pen and analyzed using GC/MS with electron ionization to assess how emission product identity and concentration changes as a function of temperature. In addition, pure pyrolysis of VEA without the influence of the device was also investigated using a tube furnace to investigate potential catalysis by the device itself. The results from this study contribute to our current understanding of the toxicity mechanisms underlying VEA vaping emissions and have significant implications for the potential health risks associated with the use of other e-liquids.This vape pen has set nominal voltages of 3.3, 3.8, 4.3, and 4.8 V. These voltages were confirmed using a multi-meter to measure the actual voltage of the battery upon activation.
The set-up of the temperature measurements can be seen in S1 Fig in S1 File. The protocol for the thermocouple measurement of the e-cigarette coil and oil temperatures was adapted from Chen et al. To measure the temperature at each voltage setting, the pen was connected to a fresh cartridge that was filled with VEA standard oil until the oil level sat just above the atomizer base. The oil level in the cartridge was kept consistent between each reading,cannabis grow facility as the amount of oil in the cartridge has been previously shown to affect the temperatures the coil may reach. Three 1 mm grounded k-type thermocouple wires were connected to a 4-channel data logger . One thermocouple was kept suspended to measure the temperature of ambient air as a device control. The second thermocouple was inserted into the air flow tube of the cartridge and allowed to rest on the surface of the ceramic coil. This position was chosen to record temperature across all voltage settings as it not only provided the most consistent measurements, but certain positioning of the probe resulted in the battery shutting off, likely to prevent overheating or burning in the event of the air flow tube being blocked during real-use scenarios. The third thermocouple was inserted into the glass casing of the cartridge to submerge the end of the probe in VEA oil in contact with the atomizer. The thermocouples allowed for simultaneous measurement of the coil and the parent oil in the cartridge when the battery was activated. Temperatures were recorded by the data logger every 1 s over a 1 min cycle. The vape pen was activated by holding the power button for 4 s to heat the coil, then allowed to rest for the remainder of the cycle. A total of 13 cycles–including 3 initial preconditioning cycles–were measured.The procedure for collection of VEA vaping emissions at each temperature setting was adapted from previous studies. Prior to each collection, a fresh cartridge was filled with VEA standard oil, weighed, and preconditioned by taking 3–5 puffs. The vaping emissions were collected using a cold trap apparatus maintained at -40˚C . The particle collection efficiency of the cold trap system at the flow rate used in this study has been reported previously. To collect aerosol emissions, one 4 s puff was taken at intervals of 1 min to maintain consistency with the temperature measurement procedure. Puffs were generated at each temperature using a 0.4 L min-1 air flow rate, which was controlled by a 0.46 L min-1 critical orifice connected a diaphragm pump . For each setting, the vape pen was operated until approximately 100 mg of VEA had been consumed; this consumption was typically achieved within 10–20 puffs. In instances where more puffs were required, the vape pen was allowed to rest at 20 puffs for 10–20 minutes to prevent overheating of the battery. Condensed emission products were dissolved in 1 mL of ACN, with 10 μL of 1, 3, 5-TCB solution added to each sample as an internal standard for chemical analysis. Emissions were analyzed immediately after collection or stored at -80˚C to prevent any aging effects.To determine the impact of the device on the degradation of e-liquids, pure pyrolysis of VEA oil was simulated using a tube furnace reactor system . The schematic of the set up for these experiments is shown in S2 Fig in S1 File. An alumina crucible containing 100 mg of VEA standard oil was weighed, and then placed into a high temperature quartz tube furnace capable of reaching temperatures as high as 1200˚C.
The tube furnace was initially set to 23˚C, then ramped to each temperature setting at a rate of 10˚C min-1, and then held at the target temperature for 75 minutes to allow for VEA oil to be evenly heated. Inert argon gas was flowed through the system at a rate of 0.18 L min-1 to carry the VEA pyrolysis products into cold trap apparatus kept at -40˚C. After 75 minutes, the tube furnace was programed to return to room temperature before the alumina crucible was removed and re-weighed to determine the amount of VEA that was consumed. Pyrolysis products condensed in the cold trap were dissolved in 1 mL of ACN and concentrated to 100 μL using a gentle N2 gas stream. Then, 10 μL of 1, 3, 5-TCB solution was added to each sample as an internal standard for chemical analysis.Fig 1 shows the temperature profiles of the e-cigarette coil and VEA oil in the cartridge operated at each voltage setting. Peak coil temperature at each voltage setting was fairly consistent between each measurement with no significant increase after consecutive use, which agrees with previous reports. Though the starting temperature after 1 min of rest increased slightly with subsequent measurements, the starting temperature never exceeded 33˚C. In contrast, the temperature of the oil in the cartridge increased with each subsequent measurement until seeming to plateau. The peak temperatures of both the coil and the oil were then taken and plotted as a function of voltage, as shown in Fig 2. Coil temperature showed a strong positive linear relationship with applied voltage , whereas oil temperature increased linearly with voltage until 41˚C , where the peak temperatures at 4.3 and 4.8 V do not significantly differ. This is likely due to the specific heat capacity of VEA; at higher voltages. Visible discoloration to the oil and wick could be seen during temperature measurements, indicating that the specific heat capacity of the oil in the cartridges may have been exceeded and part of the stored VEA may have been transformed before it is vaped .The total ion chromatographs obtained from GC/MS analysis of VEA vaping emissions produced at each temperature setting are shown in Fig 3. Overall, clear temperature dependent degradation of VEA vaping emissions can be seen as the amount and abundance of degradation products substantially increases with increasing coil temperature. Analysis of the GC/MS results revealed 19 compounds that were able to be tentatively identified based on consistent NIST MS spectral library match scores of 800 or greater. One other compound, 1-pristene, was not found in the NIST library and thus was identified based on comparison with previously reported mass spectra and a mass spectrum generated with the QCEIMS program that found signature fragments of m/z 266, 111, and 126, which are consistent with our results . A summary of the identified compounds and chemical information identified from PubChem can be found in the supporting information . Many of the products described here, such as phytol, 2,3,5-trimethyl-1,4-benzenediol and 2-hydroxy-4-methoxy-3,6-dimethyl benzaldehyde, have not been previously detected from VEA vaping to our knowledge.