Does 'Dry Hit' vaping of vitamin E acetate contribute to EVALI? Simulating toxic ketene formation during e-cigarette use.
ABSTRACT: Vitamin E acetate (VEA) is strongly linked to the outbreak of electronic-cigarette or vaping product use-associated lung injury (EVALI). It has been proposed that VEA decomposition to ketene-a respiratory poison that damages lungs at low ppm levels-may play a role in EVALI. However, there is no information available on the temperature at which VEA decomposes and how this correlates with the vaping process. We have studied the temperature-dependent kinetics of VEA decomposition using quantum chemical and statistical mechanical modelling techniques, developing a chemical kinetic model of the vaping process. This model predicts that, under typical vaping conditions, the use of VEA contaminated e-cigarette products is unlikely to produce ketene at harmful levels. However, at the high temperatures encountered at low e-cigarette product levels, which produce 'dry hits', ketene concentrations are predicted to reach acutely toxic levels in the lungs (as high as 30 ppm). We therefore hypothesize that dry hit vaping of e-cigarette products containing VEA contributes to EVALI.
Project description:Incidence of e-cigarette, or vaping, product use-associated lung injury (EVALI) has been linked to the vaping of tetrahydrocannabinol (THC) products to which vitamin E acetate (VEA) has been added. In this work we vaped THC/VEA mixtures at elevated power levels using a variety of ceramic coil vaping cartridges and a commercially available vaping device, while simultaneously measuring temperature and collecting the vaporized condensate. The collected vapor condensate was analyzed for evidence of VEA decomposition by GC/MS, GC/FT-IR/MS, and LC-APCI-HRMS/MS. Mean temperature maxima for all examined cartridges at the selected power exceeded 430°C, with a range of 375-569°C, well beyond that required for thermal decomposition of VEA. The percent recovery of VEA and Δ<sup>9</sup>-THC from the vaporized mixture in six cartridges ranged from 71.5 to 101% and from 56.4 to 88.0%, respectively. Analysis of the condensed vaporized material identified VEA decomposition products duroquinone (DQ), 1-pristene, and durohydroquinone monoacetate (DHQMA); a compound consistent with 4-acetoxy-2,3,5-trimethyl-6-methylene-2,4-cyclohexadienone (ATMMC) was also detected. The concentration of DQ produced from vaporization of the THC/VEA mixture in one cartridge was found to be 4.16 ± 0.07 μg per mg of vapor condensate.
Project description:Beginning in June of 2019, there was a marked increase in reported cases of serious pulmonary injury associated with vaping. The condition, referred to as e-cigarette or vaping product use-associated lung injury (EVALI), does not appear to involve an infectious agent; rather, a chemical adulterant or contaminant in vaping fluids is suspected. In August of 2019, the Wadsworth Center began receiving vaporizer cartridges recovered from patients with EVALI for analysis. Having no a priori information of what might be in the cartridges, we employed untargeted analyses using gas chromatography-mass spectrometry and high-resolution mass spectrometry to identify components of concern. Additionally, we employed targeted analyses used for New York medical marijuana products. Here, we report on the analyses of 38 samples from the first 10 New York cases of EVALI for which we obtained cartridges. The illicit fluids had relatively low cannabinoid content, sometimes with unusual ?9-/?8-tetrahydrocannabinol ratios, sometimes containing pesticides and many containing diluents. A notable diluent was ?-tocopheryl acetate (vitamin E acetate; VEA), which was found in 64% of the cannabinoid-containing fluids. To investigate potential sources of the VEA, we analyzed six commercial cannabis-oil diluents/thickeners. Three were found to be >95% VEA, two were found to be primarily squalane, and one was primarily ?-bisabolol. The cause(s) of EVALI is unknown. VEA and squalane are components of some personal care products; however, there is growing concern that vaping large amounts of these compounds is not safe.
Project description:Since the appearance of the E-Cigarette in the early 2000s, its industry, popularity, and prevalence have risen dramatically. In the past, E-Cigarette use with the vaping of nicotine or cannabis products had been associated with a few reported cases of lung injury. However, in 2019, thousands of cases of E-Cigarette or vaping product use-associated lung injury (EVALI) were reported in the United States. Evidence linked this outbreak with vaping of tetrahydrocannabinol (THC). We report two confirmed cases of EVALI and their associated clinical, radiologic, and pathologic features. This report supports the growing body of information regarding EVALI. It also discusses various substances, particularly vitamin E acetate, which has been suggested as a causative agent.
Project description:Electronic-cigarette, or vaping, product use-associated lung injury (EVALI) is a syndrome of acute respiratory failure characterized by monocytic and neutrophilic alveolar inflammation. Epidemiological and clinical evidence suggests a role of vitamin E acetate (VEA) in the development of EVALI, yet it remains unclear whether VEA has direct pulmonary toxicity. To test the hypotheses that aerosolized VEA causes lung injury in mice and directly injures human alveolar epithelial cells, we exposed adult mice and primary human alveolar epithelial type II (AT II) cells to an aerosol of VEA generated by a device designed for vaping oils. Outcome measures in mice included lung edema, BAL analysis, histology, and inflammatory cytokines; <i>in vitro</i> outcomes included cell death, cytokine release, cellular uptake of VEA, and gene-expression analysis. Comparison exposures in both models included the popular nicotine-containing JUUL aerosol. We discovered that VEA caused dose-dependent increases in lung water and BAL protein compared with control and JUUL-exposed mice in association with increased BAL neutrophils, oil-laden macrophages, multinucleated giant cells, and inflammatory cytokines. VEA aerosol was also toxic to AT II cells, causing increased cell death and the release of monocyte and neutrophil chemokines. VEA was directly absorbed by AT II cells, resulting in the differential gene expression of several inflammatory biological pathways. Given the epidemiological and clinical characteristics of the EVALI outbreak, these results suggest that VEA plays an important causal role.
Project description:<h4>Background</h4>The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung.<h4>Methods</h4>BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.<h4>Results</h4>State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%).<h4>Conclusions</h4>Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).
Project description:Electronic cigarette, or vaping, products (EVP) heat liquids ("e-liquids") that contain substances (licit or illicit) and deliver aerosolized particles into the lungs. Commercially available oils such as Vitamin-E-acetate (VEA), Vitamin E oil, coconut, and medium chain triglycerides (MCT) were often the constituents of e-liquids associated with an e-cigarette, or vaping, product use-associated lung injury (EVALI). The objective of this study was to evaluate the mass-based physical characteristics of the aerosolized e-liquids prepared using these oil diluents. These characteristics were particle size distributions for modeling regional respiratory deposition and puff-based total aerosol mass for estimating the number of particles delivered to the respiratory tract. Four types of e-liquids were prepared by adding terpenes to oil diluents individually: VEA, Vitamin E oil, coconut oil, and MCT. A smoking machine was used to aerosolize each e-liquid at a predetermined puff topography (volume of 55 ml for 3 s with 30-s intervals between puffs). A cascade impactor was used to collect the size-segregated aerosol for calculating the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD). The respiratory deposition of EVP aerosols on inhalation was estimated using the Multiple-Path Particle Dosimetry model. From these results, the exhaled fraction of EVP aerosols was calculated as a surrogate of secondhand exposure potential. The MMAD of VEA (0.61 μm) was statistically different compared to MCT (0.38 μm) and coconut oil (0.47 μm) but not to Vitamin E oil (0.58 μm); <i>p</i> < 0.05. Wider aerosol size distribution was observed for VEA (GSD 2.35) and MCT (GSD 2.08) compared with coconut oil (GSD 1.53) and Vitamin E oil (GSD 1.55). Irrespective of the statistical differences between MMADs, dosimetry modeling resulted in the similar regional and lobular deposition of particles for all e-liquids in the respiratory tract. The highest (~0.08 or more) fractional deposition was predicted in the pulmonary region, which is consistent as the site of injury among EVALI cases. Secondhand exposure calculations indicated that a substantial amount of EVP aerosols could be exhaled, which has potential implications for bystanders. The number of EVALI cases has declined with the removal of VEA; however, further research is required to investigate the commonly available commercial ingredients used in e-liquid preparations.
Project description:During the e-cigarette, or vaping, product use-associated lung injury (EVALI) investigation, the U.S. FDA's Forensic Chemistry Center (FCC) received numerous sample submissions from various states and other sources. Many of these products were linked directly to patients, while others were not; both categories included used and unused products. Elemental analysis using inductively coupled plasma mass spectrometry (ICP-MS) preceded by microwave-assisted decomposition was carried out on the cartridge contents of 65 of these submitted samples. Challenges encountered included limited sample, high sample viscosity, and adhesion, which necessitated sample preparation techniques not commonly used during routine elemental analysis. The elemental concentrations of contaminants including Pb, As, Cd, Cr, Ni, Cu, and Sn in tetrahydrocannabinol (THC) e-liquids associated with EVALI were determined. Nicotine e-liquid samples collected alongside the THC e-liquid samples were analyzed in tandem during method development. Several THC e-liquid samples contained Pb greater than 0.5 μg/g, while others had part per million levels of Ni, Cu, and/or Cr. This study presents the first detailed report of elemental concentrations in multiple THC e-liquid samples including those from informal/illicit sources and also delves into the method considerations needed for testing a viscous, hydrophobic sample matrix in limited quantity.
Project description:<h4>Introduction</h4>Exposure to media content can shape public opinions about tobacco. In early September 2019, the outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) became headline news in the United States.<h4>Methods</h4>In August and September 2019, we conducted two cross-sectional online surveys with current and former smokers assessing attitudes and beliefs about e-cigarettes. Study one (n = 865) was collected before the EVALI outbreak was widely covered and study two (n = 344) was collected after the outbreak had become nation-wide news. We examined differences in perceptions and beliefs between time points.<h4>Results</h4>E-cigarette harm perceptions increased between study one (mean = 2.67) and study two (mean = 2.90, p < .05). Ever-users of e-cigarettes largely account for this change. Endorsement of the belief that e-cigarettes were risky and more likely to cause lung damage compared to cigarettes increased between studies (p < .05). Seventy eight percent of participants at study two were aware of the vaping illness story. Being aware of the story was associated with more endorsement of the belief that e-cigarettes were risky to use, but not that using e-cigarettes would make the participant more likely to get damaged lungs.<h4>Discussion</h4>When the stories about the health and safety of tobacco products dominate the public information environment, it presents an opportunity to change beliefs that are frequently targeted by paid health campaigns. Changes in participant's perceptions of e-cigarettes were associated with coverage of this large news story, underscoring the importance of working to ensure that coverage is a scientifically accurate as possible.
Project description:Several cases have recently been reported concerning the development of a syndrome of acute lung injury associated with the use of electronic cigarettes, leading to respiratory failure and several deaths. We present a case of a young veteran who presented with e-cigarette vaping associated lung injury (EVALI) to a primary care clinic and who required subsequent inpatient admission and home oxygen therapy after discharge. The patient afterwards improved after a three-month course of steroids and cessation of THC-containing electronic cigarettes, consistent with previously reported cases. Furthermore, evidence on bronchoscopy and biopsy demonstrated intracellular lipid droplets in the patient's macrophages. This outpatient case of EVALI prompts primary care providers to raise suspicion of this condition, and enquire about the use of e-cigarettes, particularly THC-containing vaping products. Furthermore, in the setting of the COVID-19 pandemic, similar clinical and radiographic presentations between COVID-19 and EVALI can be seen.
Project description:The recent identification of Vitamin E acetate as one of the causal agents for the e-cigarette, or vaping, product use associated lung injury (EVALI) is a major milestone. In membrane biophysics, Vitamin E is a linactant and a potent modulator of lateral phase separation that effectively reduces the line tension at the two-dimensional phase boundaries and thereby exponentially increases the surface viscosity of the pulmonary surfactant. Disrupted dynamics of respiratory compression-expansion cycling may result in an extensive hypoxemia, leading to an acute respiratory distress entailing the formation of intraalveolar lipid-laden macrophages. Supplementation of pulmonary surfactants which retain moderate level of cholesterol and controlled hypothermia for patients are recommended when the hypothesis that the line-active property of the vitamin derivative drives the pathogenesis of EVALI holds.