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AbstractVitamin E is an important fat soluble antioxidant, its acetate is the main derivative product of vitamin E. Using metal organic framework material ZIF-8 as a catalyst, vitamin E acetate (VEA) was prepared by catalyzing the esterification reaction of D-α-tocopherol and acetic anhydride in a solvent-free system. Firstly, the preparation conditions of metal organic framework materials were studied: different imidazole ligands, different zinc ion ligands, molar concentration ratio of Zn2+ to 2-methylimidazole(2-mIM), and preparation time. The results showed that the catalytic performance of ZIF-8 was optimal when Zn(CH3COO)2·2H2O was used as the zinc source, 2-mIM was used as the imidazole ligand, the molar concentration ratio of Zn2+ / 2-mIM was 1:20, and the preparation time was 1 hour. The yield of vitamin E acetate was 86.85%. The synthesis process of VEA was optimized by single factor experiments such as substrate molar ratio, reaction time, dosage of nano enzyme, reaction temperature and so on. The results showed that the yield of vitamin E acetate reached 96.31% under the optimal conditions of n (D-α-tocopherol) =1mmol, [n (D-α-tocopherol) : n (Acetic anhydride)] =1:15, reaction time 24 h, ZIF-8 dosage 0.05 g, reaction temperature 50 °C. [ABSTRACT FROM AUTHOR]

The EVALI (E-cigarette or Vaping product use-Associated Lung Injury) epidemic of 2019 was a major public health challenge, attracting the attention of both the scientific community and the public. In a short period of time, thousands of cases of acute lung injuries and deaths were reported among e-cigarette users, previously unrelated to the risk, shedding new light on the safety of these devices and exposing gaps in the regulations regarding their use. This paper aims to review the literature on the EVALI epidemic, with particular emphasis on epidemiology, identification of the etiological agent, clinical presentation and treatment. Based on the collected data, the authors also analysed the possibilities of preventing similar events in the future, emphasizing regulations, health education of patients and increasing physicians' awareness of EVALI.

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; in vitro 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.

In the summer of 2019, a cluster of cases were observed with users of battery-operated or superheating devices presenting with multiple symptoms, such as dyspnea, cough, fever, constitutional symptoms, gastrointestinal upset, and hemoptysis, that is now termed e-cigarette, or vaping, product use-associated lung injury (EVALI). The Centers for Disease Control and Prevention reported 2807 cases within the USA leading to at least 68 deaths as of February 18, 2020. The heterogeneous presentations of EVALI make diagnosis and treatment difficult; however, treatment focused on identifying and removal of the noxious substance and providing supportive care. Vitamin E acetate (VEA) is a likely cause of this lung injury, and others have reported other components to play a possible role, such as nicotine and vegetable glycerin/propylene glycol. EVALI is usually observed in adolescents, with a history of vaping product usage within 90 days typically containing tetrahydrocannabinol, and presenting on chest radiograph with pulmonary infiltrates or computed tomography scan with ground-glass opacities. Diagnosis requires a high degree of suspicion to diagnose and exclusion of other possible causes of lung disease. Here, we review the current literature to detail the major factors contributing to EVALI and primarily discuss the potential role of VEA in EVALI. We will also briefly discuss other constituents other than just VEA, as a small number of EVALI cases are reported without the detection of VEA, but with the same clinical diagnosis.

E‐cigarette, or vaping product use‐associated lung injury (EVALI), is a severe respiratory disorder that caused a sudden outbreak of hospitalized young people in 2019. Using cannabis oil containing vaping products, including vitamin E acetate contaminants, was found to be strongly associated with EVALI. However, the underlying tissue impacts of the condition are still largely unknown. Here, we focused on the vehicle cannabinoid oil (CBD oil) and contaminant vitamin E acetate (VEA) effects on airway epithelial cells. Primary human bronchial epithelial (HBE) cultures were exposed to e‐liquid aerosols that contained CBD oil and VEA in combination or the common e‐liquid components PG/VG with and without nicotine. Cell viability analysis indicated dramatically increased cell death counts after 3 days of CBD exposure, and this effect was even higher after CBD + VEA exposure. Microscopic examination of the cultures revealed cannabinoid and VEA depositions on the epithelial surfaces and cannabinoid accumulation in exposed cells, followed by cell death. These observations were supported by proteomic analysis of the cell secretions that exhibited increases in known markers of airway epithelial toxicity, such as xenobiotic enzymes, factors related to oxidative stress response, and cell death indicators. Overall, our study provides insights into the association between cannabinoid oil and vitamin E acetate vaping and lung injury. Collectively, our results suggest that the adherent accumulation of CBD oil on airway surfaces and the cellular uptake of both CBD oil‐ and VEA‐containing condensates cause elevated metabolic stress, leading to increased cell death rates in human airway epithelial cultures. E‐cigarette, or vaping product use‐associated lung injury (EVALI), is a severe respiratory disorder that caused a sudden outbreak of hospitalized young people in 2019. Despite an association with cannabinoid containing vaping products, the underlying tissue impacts of the condition remained largely unknown. Our study reveals that the adherent accumulation of CBD oil on airway surfaces and the cellular uptake of CBD oil‐ and VEA‐containing condensates cause elevated metabolic stress, leading to increased cell death rates in human airway epithelial cultures. [ABSTRACT FROM AUTHOR]

Although much is known about Δ9-tetrahydrocannabinol and its inactive open ring isomer, cannabidiol, far less is known about the effects, metabolism, and pharmacodynamics of Δ9-tetrahydrocannabinol's double-bond isomer, Δ8-tetrahydrocannabinol. With the passage of the so-called United States "Farm Bill," which was made law in order to allow legal hemp cultivation in the United States, more needs to be known about the effects of Δ8-tetrahydrocannabinol, a double-bond isomer of Δ9-tetrahydrocannabinol, and cannabidiol (CBD), which is an open-ring isomer of Δ8-tetrahydrocannabinol. It is the aim of the review to summarize current knowledge of Δ8-tetrahydrocannabinol and CBD, including the pharmacodynamics and pharmacokinetics of CBD. Also, plant genetics, the effect of cannabinoids on the current topic of viral entry into mammalian cells, and the current practice of vaping, dabbing, and dripping are covered. [ABSTRACT FROM AUTHOR]

In the summer of 2019, a cluster of cases were observed with users of battery-operated or superheating devices presenting with multiple symptoms, such as dyspnea, cough, fever, constitutional symptoms, gastrointestinal upset, and hemoptysis, that is now termed e-cigarette, or vaping, product use-associated lung injury (EVALI). The Centers for Disease Control and Prevention reported 2807 cases within the USA leading to at least 68 deaths as of February 18, 2020. The heterogeneous presentations of EVALI make diagnosis and treatment difficult; however, treatment focused on identifying and removal of the noxious substance and providing supportive care. Vitamin E acetate (VEA) is a likely cause of this lung injury, and others have reported other components to play a possible role, such as nicotine and vegetable glycerin/propylene glycol. EVALI is usually observed in adolescents, with a history of vaping product usage within 90 days typically containing tetrahydrocannabinol, and presenting on chest radiograph with pulmonary infiltrates or computed tomography scan with ground-glass opacities. Diagnosis requires a high degree of suspicion to diagnose and exclusion of other possible causes of lung disease. Here, we review the current literature to detail the major factors contributing to EVALI and primarily discuss the potential role of VEA in EVALI. We will also briefly discuss other constituents other than just VEA, as a small number of EVALI cases are reported without the detection of VEA, but with the same clinical diagnosis. [ABSTRACT FROM AUTHOR]

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. We used mass spectrometry to evaluate the composition of aerosolized VEA condensate and the VEA deposition in murine or human alveolar macrophages. Extended vaping for 28 days versus 15 days did not worsen lung injury but caused systemic inflammation in the murine EVALI model. Vaping plus influenza increased lung water compared with virus alone. Murine alveolar macrophages exposed to vaped VEA hydrolyzed the VEA to vitamin E with evidence of oxidative stress in the alveolar space and systemic circulation. Aerosolized VEA also induced cell death and chemokine release and reduced efferocytotic function in human alveolar macrophages in vitro. These findings provide new insights into the biological mechanisms of VEA toxicity. [ABSTRACT FROM AUTHOR]

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. We used mass spectrometry to evaluate the composition of aerosolized VEA condensate and the VEA deposition in murine or human alveolar macrophages. Extended vaping for 28 days versus 15 days did not worsen lung injury but caused systemic inflammation in the murine EVALI model. Vaping plus influenza increased lung water compared with virus alone. Murine alveolar macrophages exposed to vaped VEA hydrolyzed the VEA to vitamin E with evidence of oxidative stress in the alveolar space and systemic circulation. Aerosolized VEA also induced cell death and chemokine release and reduced efferocytotic function in human alveolar macrophages in vitro. These findings provide new insights into the biological mechanisms of VEA toxicity. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the effect of adding different concentrations of vitamin E acetate to the diet on vitamin E content and the egg quality. A total of 180 Luhua laying hens aged 30 weeks were randomly divided into four groups according to the principle of similar body weight, with 45 laying hens in each group with three replicates in each group and 15 chickens in each replicate. The laying hens in control group were fed the basal diet, and the laying hens in experimental group 1, group 2 and group 3 were fed with the basal diet supplemented with 120, 240 and 480 mg/kg of vitamin E acetate, respectively. The experimental period was 30 d. The results showed that during the experiment period, the vitamin E content in the eggs of the test group was significantly higher than that of control group (P<0.05), and the vitamin E content in the eggs increased along with the increase of the concentration of vitamin E acetate added to the diet. On the 10 d, the egg weight and egg white weight of group 3 were significantly higher than that of group 1 (P<0.05). The yolk color and yolk ratio in group 1 were significantly higher than those in control group and group 3 (P<0.05). On the 20 d, the yolk weight of group 2 was significantly higher than that of control group and group 1 (P<0.05), the yolk ratio of group 2 was significantly higher than that of control group (P<0.05), and the shell thickness of group 2 was significantly higher than that of group 1 (P<0.05). On the 30 d, the ratio of egg weight, egg white weight and egg white in control group were significantly higher than those in group 1 (P<0.05). The yolk ratio of group 1 and group 2 was significantly higher than that of control group (P<0.05). The experiment indicates that vitamin E acetate can increase the content of vitamin E in egg yolk. Dietary supplementation with vitamin E acetate has a tendency to increase the weight and ratio of egg yolk. [ABSTRACT FROM AUTHOR]

The electronic cigarette (EC), was initially introduced as a safe alternative to conventional cigarette smoking While initially seemingly innocuous, over 2800 E-cigarette, or Vaping, product use-associated lung injury (EVALI) cases have been reported in the USA, with a spectrum of clinical severity ranging from mild dyspnea to overt respiratory failure In this report we highlight three EVALI cases whom presented with dyspnea and a variety of non-specific symptoms. Diagnostic imaging demonstrated bilateral reticular infiltrates and ground-glass opacities with lymphadenopathy. Clinically, patients failed to respond to empiric antibiotics but improved after initiating steroids. Consistent with prior case series, our patients reported exposure to EC liquids containing tetrahydrocannabinol (THC)/cannabidiols (CBD) additives, suggesting Vitamin E acetate as the potentially harmful constituent. In this case series and review, we not only summarize prior clinical studies that have evaluated the effects of vaping on cardiopulmonary function as well as case reports on EVALI, but also discuss the pathophysiology of vaping and EVALI. It remains unclear not only why some individuals develop EVALI, but why the clinical and pathological presentations vary. EVALI remains a significant public health concern and clinicians must maintain a high index of suspicion for this novel phenomenon.

As of February 18, 2020, the e-cigarette, or vaping, product use associated lung injury (EVALI) outbreak caused the hospitalization of a total of 2,807 patients and claimed 68 lives in the United States. Though investigations have reported a strong association with vitamin E acetate (VEA), evidence from reported EVALI cases is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC or non-THC products. This study characterized chemicals evolved when diluent oils were heated to temperatures that mimic e-cigarette, or vaping, products (EVPs) to investigate production of potentially toxic chemicals that might have caused lung injury. VEA, vitamin E, coconut, and medium chain triglyceride (MCT) oil were each diluted with ethanol and then tested for constituents and impurities using a gas chromatograph mass spectrometer (GC/MS). Undiluted oils were heated at 25°C (control), 150°C, and 250°C in an inert chamber to mimic a range of temperatures indicative of aerosolization from EVPs. Volatilized chemicals were collected using thermal desorption tubes, analyzed using a GC/MS, and identified. Presence of identified chemicals was confirmed using retention time and ion spectra matching with analytic standards. Direct analysis of oils, as received, revealed that VEA and vitamin E were the main constituents of their oils, and coconut and MCT oils were nearly identical having two main constituents: glycerol tricaprylate and 2-(decanoyloxy) propane-1,3-diyl dioctanoate. More chemicals were measured and with greater intensities when diluent oils were heated at 250°C compared to 150°C and 25°C. Vitamin E and coconut/MCT oils produced different chemical emissions. The presence of some identified chemicals is of potential health consequence because many are known respiratory irritants and acute respiratory toxins. Exposure to a mixture of hazardous chemicals may be relevant to the development or exacerbation of EVALI, especially when in concert with physical damage caused by lung deposition of aerosols produced by aerosolizing diluent oils.

During the summer of 2019, cases of lung injury associated with vaping emerged in North America, including among individuals who reported exclusive use of nicotine vaping liquids. Once vitamin E acetate was identified as a potential causative agent a quantitative method based on a simple sample dilution, separation by gas chromatography and analysis by triple quadrupole mass spectrometry (GC MSMS) was developed. Method detection limit (MDL) and limit of quantification (LOQ) were determined at 0.159 µg/mL and 0.505 µg/mL, respectively. The analysis was performed on a subset of 203 commercially sourced nicotine containing vaping liquids of various flavour profile and nicotine range (nicotine free-59 mg/mL) from an internal inventory. The target analyte, Vitamin E Acetate, was not detected in any samples analyzed, as expected, given the reported detection in literature and high association of the chemical with cannabis and not nicotine containing vaping products.

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); p < 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.

Abstract Pulmonary alveolar proteinosis (PAP) can be due to primary autoimmune and secondary causes, including e‐cigarette, or vaping, product use‐associated lung injury. We present a 33‐year‐old male presenting with PAP and a history of vaping. Serum anti‐granulocyte‐macrophage colony‐stimulating factor antibodies were present. Vitamin E (VE), but not VE acetate, was detected in bronchoalveolar lavage. This is the first report of potential association between vaping and autoimmune PAP.

E-cigarette or vaping product use-associated lung injury (EVALI) is a serious pulmonary condition that is associated with the extended use of certain vaping products. EVALI was first characterized in the summer of 2019 and has since been reported in all 50 U.S. states. From August 2019 through June 2021, the New York State Department of Health has reported more than 197 confirmed cases emanating from all regions of the state. The Wadsworth Center at the New York State Department of Heath received vaping cartridges recovered from EVALI patients for chemical analysis of their contents. Untargeted analytical methods using gas chromatography-mass spectrometry and liquid chromatography-high-resolution mass spectrometry as well as targeted analyses for a variety of analytes including cannabinoids, pesticides, vitamin E acetate (VEA) and mycotoxins were used to characterize the composition of the vaping fluids and several commercial vaping fluid additives. From the analyses of the 284 e-cigarette devices recovered from patients, 82 were found to be nicotine-containing pods, and 202 devices containing cannabis oil, apparently from unauthorized or black-market dealers. The fluids from the cannabis-oil cartridges tended to have lower levels of THCs (Δ9-tetrahydrocannabinol + Δ8-tetrahydrocannabinol) and total cannabinoids compared with those of commercially produced formulations and contained significant levels of diluents including VEA, medium-chain triglycerides, polyethylene glycol, and castor oil. VEA was the diluent most frequently detected, which was present in 132 (65.3%) of the vaping fluids that contained cannabis oil. When present, VEA ranged from 2.0 to 67.8% of the total mass of the oil with a mean content of 37.0%. In some cases, two or three diluents were detected in the same sample. The ratio of VEA to THCs varied widely, from 0.07 to 5.34. VEA and specifically the high ratios of VEA to THCs in black-market vaping fluids may be causative in EVALI. The safety of additional components and additives that are present in vaping fluids are likewise of concern.

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 Δ9-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.

E-cigarette, or vaping, product (EVP) use has increased dramatically in the United States over the last 4 years, particularly in youth and young adults. Little information is available on the chemical contents of these products. Typically, EVPs contain an active ingredient such as nicotine, CBD, or THC dissolved in a suitable solvent that facilitates aerosol generation. One EVP solvent, vitamin E acetate (VEA), has been measured in EVP liquids associated with lung injury. However, no validated analytical methods for measuring VEA in the aerosol from these devices was previously available. Therefore, we developed a high throughput isotope dilution LC-MS/MS method to simultaneously measure VEA and three other related tocopherols in aerosolized EVP samples. The assay was precise, with VEA repeatability ranging from 4.0 to 8.3% and intermediate precision ranging from 2.5 to 6.7%. Similar precision was obtained for the three other tocopherols measured. The LODs for the four analytes ranged from 8.85 × 10−6 to 2.28 × 10−5 μg analyte per mL of aerosol puff volume, and calibration curves were linear (R2 > 0.99). This method was used to analyze aerosol emissions of 147 EVPs associated with EVALI case patients. We detected VEA in 46% of the case-associated EVPs with a range of 1.87 × 10−4–74.1 µg per mL of aerosol puff volume and mean of 25.1 µg per mL of aerosol puff volume. Macro-levels of VEA (>0.1% w/w total aerosol particulate matter) were not detected in nicotine or cannabidiol (CBD) products; conversely 71% of the EVALI associated tetrahydrocannabinol (THC) products contained macro-levels of VEA. Trace levels of other tocopherol isoforms were detected at lower rates and concentrations (α-tocopherol: 41% detected, mean 0.095 µg analyte per mL of aerosol puff volume; γ-tocopherol: 5% detected, mean 0.0193 µg analyte per mL of aerosol puff volume; δ-tocopherol: not detected). Our results indicate that VEA can be efficiently transferred to aerosol by EVALI-associated EVPs vaped using a standardized protocol.

Background: Vitamin E acetate (VEA) has come under significant scrutiny due to its association with E-cigarette or vaping product use–associated lung injury (EVALI). Various theoretical mechanisms have been proposed for toxicity, including tocopherol (vitamin E)–mediated surfactant damage, recruitment of inflammation, and pyrolysis of acetate to the pulmonary irritant ketene. Objective: Characterize studies in mammals evaluating inhaled VEA, vitamin E analogues, or pyrolyzed acetate that describe subsequent effects on the lung. Eligibility: Research in all languages from time of inception to October 1, 2020, regarding mammals (human or animal) exposed to inhaled vitamin E analogues, or any compound containing acetate administered via inhalation after pyrolysis, and subsequent description of pulmonary effect. Sources of evidence: Ovid MEDLINE, Scopus, and Web of Science Core Collection. Results: In total, 786 unique articles were identified. After duplicate reviewer screening, 16 articles were eligible for inclusion. Tocopherol was evaluated in 68.8% (11/16) of the studies, VEA in 18.8% (3/16), and both VEA and tocopherol were evaluated in 12.5% (2/16). Of the five studies evaluating VEA, it was given by pyrolysis in 60.0% (3/5). No human studies were identified. All included trials were conducted on non-human mammals: 75.0% (12/16) rodent models and 25.0% (4/16) sheep models. Outcomes assessed were heterogeneous and included 57 unique outcomes. Conclusions: Several questions still exist regarding the pulmonary toxicity of inhaled tocopherol and VEA. More studies are needed to determine whether tocopherol alone (i.e., without acetate) can cause pulmonary injury. Additionally, further studies of VEA should evaluate the impact that pyrolysis and co-administration with other compounds, such as tetrahydrocannabinol, have on the toxic potential of VEA. [ABSTRACT FROM AUTHOR]

In the summer of 2019, an epidemic of e-cigarette or vaping product use associated lung injury (EVALI) broke out in the United States of America. EVALI is a lung disease that can be severe and life-threatening. It should be emphasized that EVALI is not a clinical diagnosis, but surveillance case definition. Due to the profile of users of such devices, the pathology mainly affects young adults, although cases of EVALI have been reported in almost all age groups, from teenage children to seniors. The worst prognosis is in patients over 35 years of age, with accompanying diseases. A significant number of patients declared the use of products containing tetrahydrocannabinol (THC). The most likely factor responsible for the occurrence of EVALI is vitamin E acetate, which is sometimes added to liquids necessary for the use of electronic cigarette type devices, especially those liquids that contain THC. Nevertheless, it is possible that other substances used in liquids may also be a causative factor. Typical for EVALI are respiratory, gastrointestinal and systemic symptoms, while in imaging tests, a characteristic feature of EVALI is the presence of opacities on the chest radiogram and ground-glass clouds on computed tomography scans. In the course of this disease, respiratory failure often occurs (58%). In the vast majority of cases oxygen substitution is necessary. Currently, the best treatment of EVALI is considered to be the administration of systemic glucocorticosteroids. Over 90% of patients with EVALI required hospitalization, while the mortality rate was about 2.42%. Median age of the fatalities was 51 years. The aim of this review is to summarise the available information on EVALI and to consider possible causative factors and pathomechanism. [ABSTRACT FROM AUTHOR]

Aim: To describe an outbreak of lung injuries in 2019 among people who vaped in the United States (type of injuries, people afflicted, substances vaped and cause of the injuries) and to analyse critically the regulatory responses of public health authorities and the media reporting of the outbreak. Methods: Case studies of the reporting of the e‐cigarette or vaping product use associated lung injury (EVALI) outbreak. We examined data on the number of cases of lung injury provided by the US Centers for Disease Control (CDC), public advice on the causes of the outbreak provided by the CDC and the Food and Drug Administration (FDA), major media reports of the outbreak and proposed regulatory responses by governments in the United States, Australia and the United Kingdom. Results: The CDC initially suggested that the cause of the outbreak was nicotine vaping because the outbreak followed a large increase in nicotine vaping among US adolescents. Case–control studies revealed that the majority of cases had vaped illicit cannabis oils that were contaminated by vitamin E acetate. The CDC's public advice and the media were slow to report the evidence on the role of cannabis vaping. Popular government regulatory proposals—bans on sales of nicotine flavours and vaporizers—were based on the assumption that nicotine vaping was the cause of the outbreak. Conclusions: Media reporting in the United States, Australia and the United Kingdom of the US Centers for Disease Control's analysis of the causes of the e‐cigarette or vaping product use associated lung injury outbreak contributed to regulatory over‐reactions to nicotine vaping by the public health community. [ABSTRACT FROM AUTHOR]

Small scale observational evidence suggested that Vitamin E (VE) might play beneficial role in human and animal respiratory conditions of various origin by stabilizing surfactant functions. The intra-aleveolar VE level is directly proportionate to the lung's response to inflammation. Electronic cigarette or vaping associated lung injury was a dominantly respiratory syndrome in the United States with seemingly strong association between potential Vitamin E acetate inhalation exposure and the onset of symptoms. This systematic review intended to assess if there was previous evidence of any potential respiratory/gastrointestinal toxicity associated with Vitamin E acetate or any of its derivatives. A systematic review was constructed and prospectively registered at PROSPERO to search important clinical databases between 2000 and 2020 for full text human articles investigating the effect of VEA or any of its derivatives administered via any route (oral/parenteral/aerosolised) in adults with any respiratory conditions. Out of 363 records investigating the effect of VEA and/or its derivatives/isomers in (any) lung injury (inflammatory, oxidative, infective, asthma/COPD) seven articles qualified. The papers reported various surrogate outcomes (APACHEII score, spirometry, etc) with equivocal results. There was one case report of harmful exposure to both Vitamin E (intramuscular) and Vitamin E acetate (topical). The present review found evidence of neither harm nor any significant clinical improvement associated with the administration of VEA or any derivatives via any route in adult inflammatory lung conditions however, the articles were of low-level evidence. Further studies are needed to correct flaws in research to explore the role of Vitamin E in pulmonology. [ABSTRACT FROM AUTHOR]

Keywords: acute lung injury; e-cigarette; EVALI; toxicology; vitamin E acetate EN acute lung injury e-cigarette EVALI toxicology vitamin E acetate 426 431 6 12/26/20 20210101 NES 210101 The Centers for Disease Control and Prevention (CDC), the US Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders have investigated a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). However, evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either tetrahydrocannabinol (THC) or non-THC products, in some of the reported EVALI cases. Evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC or non-THC products, in some of the reported EVALI cases.[4] SP , sp [7] SP , sp [10] What Is VEA, and Does It Differ From Vitamin E? None of the products seized in 2018 contained VEA; however, the 20 products seized in 2019 and the 24 products submitted by 12 patients with EVALI in 2019 contained VEA. [Extracted from the article]

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; in vitro 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 byATII 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. [ABSTRACT FROM AUTHOR]

The electronic cigarette (EC), was initially introduced as a safe alternative to conventional cigarette smoking While initially seemingly innocuous, over 2800 E-cigarette, or Vaping, product use-associated lung injury (EVALI) cases have been reported in the USA, with a spectrum of clinical severity ranging from mild dyspnea to overt respiratory failure In this report we highlight three EVALI cases whom presented with dyspnea and a variety of non-specific symptoms. Diagnostic imaging demonstrated bilateral reticular infiltrates and ground-glass opacities with lymphadenopathy. Clinically, patients failed to respond to empiric antibiotics but improved after initiating steroids. Consistent with prior case series, our patients reported exposure to EC liquids containing tetrahydrocannabinol (THC)/cannabidiols (CBD) additives, suggesting Vitamin E acetate as the potentially harmful constituent. In this case series and review, we not only summarize prior clinical studies that have evaluated the effects of vaping on cardiopulmonary function as well as case reports on EVALI, but also discuss the pathophysiology of vaping and EVALI. It remains unclear not only why some individuals develop EVALI, but why the clinical and pathological presentations vary. EVALI remains a significant public health concern and clinicians must maintain a high index of suspicion for this novel phenomenon. [ABSTRACT FROM AUTHOR]

Background: Cases of e-cigarette or vaping product use-associated lung injury (EVALI) have rapidly reached epidemic proportions, yet there remain limited reports within the literature on the associated imaging findings. Objective: We describe the most common imaging findings observed on chest computed tomography (CT) and chest radiograph (CXR) at presentation and at short-term follow-up at our major pediatric hospital. Materials and methods: A retrospective review of the electronic medical records was performed on all patients with suspected EVALI who were treated at a major pediatric hospital and 11 patients were included for analysis. Two board-certified pediatric radiologists then categorized the CXRs as either normal or abnormal, and further performed a systematic review of the chest CTs for imaging findings in the lungs, pleura and mediastinum. Interrater discordance was reconciled by consensus review. Results: The 11 patients (9 males:2 females) ranged in age from 14 to 18 years. Gastrointestinal and constitutional symptoms were present in all patients, whereas shortness of breath and cough were reported in 5/11 and 6/11 patients, respectively. The CXR was abnormal in 10/11 patients, whereas all chest CTs were abnormal. The most common CT findings included consolidation, ground-glass opacities, interlobular septal thickening, lymphadenopathy and crazy-paving pattern. Almost all patients demonstrated subpleural sparing, and less than half also demonstrated peribronchovascular sparing. There was complete or near-complete resolution of imaging abnormalities in 5/6 patients with a median follow-up duration of 114 days. Conclusion: Pulmonary opacities with subpleural and peribronchovascular sparing was a commonly observed pattern of EVALI in the pediatric population at this institution. A CXR may not be sufficiently sensitive in diagnosing EVALI, and radiologists and clinicians should exercise caution when excluding EVALI based on the lack of a pulmonary opacity. Caution should also be exercised when excluding EVALI solely based on the lack of respiratory symptoms. Despite extensive pulmonary involvement at presentation, findings may resolve on short-term follow-up imaging. [ABSTRACT FROM AUTHOR]

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The prevalence of vaping has seen a dramatic increase in the last decade, especially among adolescent populations. This article discusses the background, prevalence, and associated risk factors of e-cigarettes. [ABSTRACT FROM AUTHOR]

Vitamin E acetate (VEA) has come under significant scrutiny due to its association with e-cigarette, or vaping, product use-associated lung injury (EVALI). In 1965, Sir Austin Bradford Hill proposed a set of criteria used to critically assess an association for causality. In this article, we apply the Bradford Hill causation criteria to VEA and the EVALI outbreak to clarify what further areas of study are needed to strengthen the causal argument. Additionally, we highlight the need for systematized approaches to rapidly identify the cause of mass poisoning events of unknown etiology. [ABSTRACT FROM AUTHOR]

In 2019, the Centers for Disease Control and Prevention noted the association of vaping and acute respiratory distress syndrome. Although the number of new cases has decreased, new cases are still appearing. [ABSTRACT FROM AUTHOR]

A combined analytical, theoretical, and experimental study has shown that the vaping of vitamin E acetate has the potential to produce exceptionally toxic ketene gas, which may be a contributing factor to the upsurge in pulmonary injuries associated with using e-cigarette/vaping products. Additionally, the pyrolysis of vitamin E acetate also produces carcinogen alkenes and benzene for which the negative longterm medical effects are well recognized. As temperatures reached in vaping devices can be equivalent to a laboratory pyrolysis apparatus, the potential for unexpected chemistries to take place on individual components within a vape mixture is high. Educational programs to informof the danger are nowrequired, as public perception has grown that vaping is not harmful. [ABSTRACT FROM AUTHOR]

The use of e-cigarettes in the US has been reported widely across various age groups, socioeconomic backgrounds, and ethnicities. Of concern is the use of e-cigarettes in adolescent and young adult “never before smokers.” Several public health organizations have made recommendations pertaining to e-cigarette use. This article summarizes the latest recommendations. [ABSTRACT FROM AUTHOR]

Pulmonary alveolar proteinosis (PAP) can be due to primary autoimmune and secondary causes, including e‐cigarette, or vaping, product use‐associated lung injury. We present a 33‐year‐old male presenting with PAP and a history of vaping. Serum anti‐granulocyte‐macrophage colony‐stimulating factor antibodies were present. Vitamin E (VE), but not VE acetate, was detected in bronchoalveolar lavage. This is the first report of potential association between vaping and autoimmune PAP. [ABSTRACT FROM AUTHOR]

This work is concerned with development and validation of two simple, specific, accurate and precise spectrophotometric methods for determination of two hepatoprotective drugs, silymarin (SR) and vitamin E acetate (VE), in their binary mixtures and a pharmaceutical formulation. Method A is a ratio difference spectrophotometric method (RDSM), while method B is a mean centering of ratio spectra spectrophotometric one (MCR). In both methods, the absorption spectra of each drug were recorded, divided by a suitable divisor, then the obtained ratio spectra were subtracted at two specific wavelengths in the ratio difference spectrophotometric method, while the obtained ratio spectra were mean centered in the mean centering of ratio spectra spectrophotometric method. The specificity of the developed methods was assessed by analyzing different laboratory prepared mixtures containing SR and VE. The two methods were validated as per the International Conference on Harmonization guidelines. Accuracy, precision and repeatability were found to be within the acceptable limits. [ABSTRACT FROM AUTHOR]

Background: Lichen sclerosus (LS) is a disease of the skin of unclear etiology that can occur in the foreskin. Topical therapy with corticosteroids is recommended, but they can have side effects. Objectives: We aimed to compare the effects of ozonides with vitamin E acetate (OZOILE) versus topical corticosteroid in children undergoing circumcision. Method: Twenty children undergoing circumcision were treated before surgery: 10 children with OZOILE cream and 10 with 0.1% mometasone furoate once a day for 7 days. Ten age-matched patients with LS of the foreskin without any treatment were recruited as controls. Transcript levels of proinflammatory and anti-inflammatory cytokines and e-cadherin were evaluated in removed foreskins by qRT-PCR. Results: OZOILE and steroid topical treatment produced a similar reduction of TNF-α and IL-1β mRNA levels in foreskins from patients with LS when compared to untreated patients (p < 0.001). OZOILE and steroid treatment caused an increase in the transcript levels of IL-13 and e-cadherin in the foreskin of patients affected by LS in comparison to untreated foreskin (p < 0.001). Conclusions: On the basis of our biochemical data, a randomized clinical trial might be useful to verify the actual clinical effect of OZOILE as alternative treatment to corticosteroids in children affected by LS of the foreskin. [ABSTRACT FROM AUTHOR]

The resinous exudate produced by Commiphora myrrha (Nees) Engl. is commonly known as true myrrh and has been used since antiquity for several medicinal applications. Hundreds of metabolites have been identified in the volatile component of myrrh so far, mainly sesquiterpenes. Although several efforts have been devoted to identifying these sesquiterpenes, the phytochemical analyses have been performed by gas-chromatography/mass spectrometry (GC–MS) where the high temperature employed can promote degradation of the components. In this work, we report the extraction of C. myrrha by supercritical CO2, an extraction method known for the mild extraction conditions that allow avoiding undesired chemical reactions during the process. In addition, the analyses of myrrh oil and of its metabolites were performed by HPLC and GC–MS. Moreover, we evaluated the antiviral activity against influenza A virus of the myrrh extracts, that was possible to appreciate after the addition of vitamin E acetate (α-tocopheryl acetate) to the extract. Further, the single main bioactive components of the oil of C. myrrha commercially available were tested. Interestingly, we found that both furanodienone and curzerene affect viral replication by acting on different steps of the virus life cycle.

Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder, considered the male genital variant of lichen sclerosus. Anti-inflammatory drugs are commonly used in BXO. We evaluated the effects of an innovative formulation of ozonated olive oil with vitamin E acetate (OZOILE®) on the inflammatory status and tissue remodeling in male children with BXO. The mRNA transcripts of proteins involved either in inflammation or in dynamics of tissue regeneration were analyzed by quantitative real-time PCR, in foreskins affected by BXO removed from patients untreated or treated with OZOILE® cream for 7 days before circumcision. We found a significant reduction in mRNA levels of IL-1β, TNF-α, INF-γ, transglutaminase 2 and NOS2 in foreskins treated with OZOILE® in comparison to untreated ones (p < 0.001). No significant differences were observed in NF-κB activation in the specimens obtained from treated and untreated patients. Hence, OZOILE® treatment up-regulated hypoxia-inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF) and E-cadherin gene expression (p < 0.001). The treatment with OZOILE® showed effective results in children affected by BXO by reducing the inflammatory process and stimulating mechanisms for tissue regeneration of the foreskin. A randomized clinical trial on a large number of children affected by BXO might be useful to verify the efficacy of topical treatment with OZOILE®. [ABSTRACT FROM AUTHOR]

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 Δ9-/Δ8-tetrahydrocannabinol ratios, sometimes containing pesticides and many containing diluents. A notable diluent was α-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 α-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.

In this study the experimental deposition of vitamin E microcapsules by padding technique on the textile support made of 50% cotton and 50% polyamide high tenacity Nm 50/1 were performed. The preliminary preparation of textile materials has been made in four consecutive sequences: hot alkaline treatment in absence of NaOH, bleaching, drying and curing. In the pretreatment of textile materials the crosslinking agent Itobinder AG is used, which is an anionic emulsion based on the acrylic copolimer, being followed by the application of a dispersion with content of vitamin E microcapsules. In the present raport the evaluation of obtained performances was made through SEM, GC and FTIR-ATR analysis. By SEM has been determined the wash durability of deposition of vitamin E microcapsules before and after one washing cycle. Following qualitative analysis by Gas-Chromatography coupled with Mass Spectrometry and Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection absorption the related compoundes presents on the surface of the textile materials were identified. After retention time the vitamin E acetate is found with preponderance in all chromatograms at 15, 70 min with aproximation. Also by FTIR-ATR the presence of vitamin E acetate is confirmed by the apparition of a new peak at 1731 cm-1 and changes of intensity of various peaks, especially in the fingerprint region of the spectra of the functionalized fabrics. [ABSTRACT FROM AUTHOR]