An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury.
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ABSTRACT:
SUBMITTER: Bhat TA
PROVIDER: S-EPMC7299285 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury.
Bhat Tariq A TA Kalathil Suresh G SG Bogner Paul N PN Blount Benjamin C BC Goniewicz Maciej L ML Thanavala Yasmin M YM
The New England journal of medicine 20200226 12
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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.
| S-EPMC7422838 | biostudies-literature
Project description:BackgroundThe 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.MethodsBAL 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.ResultsState 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%).ConclusionsVitamin 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.).
| S-EPMC7032996 | biostudies-literature
Project description: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.
| S-EPMC7470376 | biostudies-literature
Project description:BackgroundAcute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions.MethodsWe established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9% + Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS.ResultsAfter adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62-0.79) in the left lung vs 0.14 (IQR 0.14-0.16; p < 0.05) in the right lung, confirming unilateral ALI. A significant and sustained drop in pulmonary compliance (Cdyn) of the left lung occurred immediately, whereas Cdyn of the right lung remained unchanged (p < 0.05). BAL fluid concentrations of interleukin-6 and -8 were increased in both lungs.ConclusionsWe established a model of unilateral ALI in pigs, confirmed by histopathology, and typical changes in respiratory mechanics and an inflammatory response. This thoroughly evaluated model could serve as a basis for future studies and for comparing pathophysiological and pharmacological changes in the uninjured and injured lung within the same animal.
| S-EPMC9701381 | biostudies-literature
Project description:BackgroundScientists identified vitamin E acetate (VEA) and "Dank Vapes" (a fake brand of tetrahydrocannabinol [THC] vaping products) as contributors to the 2019-2020 outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). On social media, people who post about vaping or THC discussed the causes of EVALI. We examined whether Reddit conversations may have served as early signals of the outbreak.MethodsWe collected Reddit posts from March 2018 to February 2020 on vaping- and THC-related subreddits that mentioned VEA or Dank Vapes. We identified peaks in post volume, examined post content, and used natural language processing to identify terms most characteristic of posts.ResultsThere were almost no posts about VEA before EVALI. Subsequently, there were two peaks, both referencing media coverage of scientific findings that linked VEA to EVALI. Discussion regularly referenced concerns about the legitimacy of Dank Vapes before EVALI; peaks in posts were largely unrelated to scientific findings or media coverage of those findings. The terms most characteristic of VEA posts were EVALI-related; those most characteristic of Dank Vapes posts were about quality or legitimacy.ConclusionsAlthough posts about VEA and Dank Vapes did not predict the outbreak, the public health community could use social media to encourage people who vape or use THC to report future health concerns (e.g., through FDA's Safety Reporting Portal). Researchers and regulators could also use social media to see if potentially problematic products, such as Dank Vapes, have a history of concern among individuals who use those products.
| S-EPMC8728682 | biostudies-literature
Project description:In late 2019, the outbreak of e-cigarette or vaping-associated lung injuries (EVALIs) in the United States demonstrated to the public the potential health risks of vaping. While studies since the outbreak have identified vitamin E acetate (VEA), a diluent of tetrahydrocannabinol (THC) in vape cartridges, as a potential contributor to lung injuries, the molecular mechanisms through which VEA may cause damage are still unclear. Recent studies have found that the thermal degradation of e-liquids during vaping can result in the formation of products that are more toxic than the parent compounds. In this study, we assessed the role of duroquinone (DQ) in VEA vaping emissions that may act as a mechanism through which VEA vaping causes lung damage. VEA vaping emissions were collected and analyzed for their potential to generate reactive oxygen species (ROS) and induce oxidative stress-associated gene expression in human bronchial epithelial cells (BEAS-2B). Significant ROS generation by VEA vaping emissions was observed in both acellular and cellular systems. Furthermore, exposure to vaping emissions resulted in significant upregulation of NQO1 and HMOX-1 genes in BEAS-2B cells, indicating a strong potential for vaped VEA to cause oxidative damage and acute lung injury; the effects are more profound than exposure to equivalent concentrations of DQ alone. Our findings suggest that there may be synergistic interactions between thermal decomposition products of VEA, highlighting the multifaceted nature of vaping toxicity.
| S-EPMC8860880 | biostudies-literature
Project description:Acute lung injury (ALI) is a critical condition with limited treatment options. This study evaluates the therapeutic potential of human fetal lung-derived mesenchymal stem cells (hFL-MSCs) in an experimental model of ALI. Our proof-of-concept findings suggest a paradigm shift in the approach to cell sourcing for lung diseases, proposing that fetal lung cells may be potential targets for stem cell differentiation studies when the derived cells are intended to be used for lung cell therapy. After characterizing hFL-MSCs, 18-week fetal lung cells were intratracheally instilled into rats with bleomycin-induced ALI. All the animals were evaluated on days 3 - 28 post-injury for cell count and the cytokines in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, lung tissue histological staining and expression of an extracellular matrix component, inflammatory and fibrotic genes. The findings confirm mesenchymal stem cell identity of the isolated cells and stability in their cell cycle distribution. Analysis of BALF showed that immune cell response to acute inflammation and adaptive immunity was significantly ameliorated by cell therapy with hFL-MSCs. Same results were confirmed by the levels of IL-6, TNF-α, IL-10 and NO in BALF, the lung wet/dry weight ratio and histopathological analysis of lung tissues after H&E and Masson's trichrome staining. Effective modulation of key pro-inflammatory (Il6, Tnf, Il1b), pro-fibrotic (Tgfb1) and Col1a1 genes were also confirmed after therapy with hFL-MSCs. Our findings suggest that fetal lung tissue-specific stem cells are viable options for lung cell therapy and could be considered as targets for engineering of regenerative cells for lung diseases.
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Project description:Inhalation of aerosolized products generated by different electronic devices is called vaping. E-cigarettes or Vaping product use Associated Lung Injury (EVALI) outbreak peaked in August-September 2019 and gradually declined. EVALI remains a diagnosis of exclusion which presents as an acute lung injury in the vaping population. Vitamin E acetate and its products are implicated as one of the cytotoxic agents causing airway centered pneumonitis. Lipid laden macrophages are found in samples of BAL fluid but their role in cytopathology of the disease remains unclear. We present a 57 years old man who came to the emergency department at Monmouth Medical Center, New Jersey in fall, 2019. Reportedly he has been vaping THC about 100g every day for past three days. At initial presentation, he had fever, shortness of breath and hypoxia requiring supplemental oxygen. He was empirically treated with levofloxacin 500 mg for five days without a significant improvement in his symptoms. Non-contrast chest CT scan showed bilateral ground-glass opacities, indicative of diffuse alveolar damage. He underwent flexible bronchoscopy to rule out infective pneumonia followed by auto-immune work-up that was non-conclusive. He was given 1 mg/kg methylprednisolone with a quick taper of oral steroids leading to the resolution of symptoms. At six months follow-up, imaging showed near resolution of ground-glass opacities.
| S-EPMC7394920 | biostudies-literature
Project description:"E-Cigarette (e-cig) Vaping-Associated Acute Lung Injury" (EVALI) has been linked to vitamin-E-acetate (VEA) and Δ-9-tetrahydrocannabinol (THC), due to their presence in patients' e-cigs and biological samples. Lacking standardized methodologies for patients' data collection and comprehensive physicochemical/toxicological studies using real-world-vapor exposures, very little data are available, thus the underlying pathophysiological mechanism of EVALI is still unknown. This review aims to provide a comprehensive and critical appraisal of existing literature on clinical/epidemiological features and physicochemical-toxicological characterization of vaping emissions associated with EVALI. The literature review of 161 medical case reports revealed that the predominant demographic pattern was healthy white male, adolescent, or young adult, vaping illicit/informal THC-containing e-cigs. The main histopathologic pattern consisted of diffuse alveolar damage with bilateral ground-glass-opacities at chest radiograph/CT, and increased number of macrophages or neutrophils and foamy-macrophages in the bronchoalveolar lavage. The chemical analysis of THC/VEA e-cig vapors showed a chemical difference between THC/VEA and the single THC or VEA. The chemical characterization of vapors from counterfeit THC-based e-cigs or in-house-prepared e-liquids using either cannabidiol (CBD), VEA, or medium-chain triglycerides (MCT), identified many toxicants, such as carbonyls, volatile organic compounds, terpenes, silicon compounds, hydrocarbons, heavy metals, pesticides and various industrial/manufacturing/automotive-related chemicals. There is very scarce published toxicological data on emissions from THC/VEA e-liquids. However, CBD, MCT, and VEA emissions exert varying degrees of cytotoxicity, inflammation, and lung damage, depending on puffing topography and cell line. Major knowledge gaps were identified, including the need for more systematic-standardized epidemiological surveys, comprehensive physicochemical characterization of real-world e-cig emissions, and mechanistic studies linking emission properties to specific toxicological outcomes.
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Project description:Gene expression profiling was performed in lung tissues from an animal model of sepsis challenged with injurious and non-injurious mechanical ventilation to unravel the molecular pathways involved in acute lung injury. Sepsis was induced in male Sprague Dawley rats by means of cecal ligation and puncture. Septic rats were randomly allocated to three distinct groups: spontaneous breathing, mechanically ventilated with high tidal volume with zero positive end expiratory pressure (PEEP) and with low tidal volume and 10 cmH2O of PEEP. Comparisons were performed against an unventilated control group.
2015-07-01 | E-MTAB-2673 | biostudies-arrayexpress