Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

Blount, Benjamin C.; Karwowski, Mateusz P.; Shields, Peter G.; Morel-Espinosa, Maria; Valentín-Blasini, Liza; Gardner, Michael L. G.; Braselton, Martha; Brosius, Christina; Caron, Kevin T.; Chambers, David M.; Corstvet, Joseph; Cowan, Elizabeth A.; Jesús, Víctor R. De; Espinosa, Patricio; Fernández, Carolina; Holder, Cory; Kuklenyik, Zsuzsanna; Kusovschi, Jennifer D; Newman, Cody; Reis, Gregory B; Rees, Jon; Reese, C. C.; Silva, Lalith; Seyler, Tiffany; Song, Min-Ae; Sosnoff, Connie S.; Spitzer, Carleen; Tevis, Denise S.; Wang, Lanqing; Watson, Cliff; Wewers, Mark D.; Xia, Baoyun; Heitkemper, Douglas T.; Ghinai, Isaac; Layden, Jennifer E.; Briss, Peter A.; King, Brian A.; Delaney, Lisa; Jones, Christopher M.; Baldwin, Grant T.; Patel, Anita; Meaney‐Delman, Dana; Rose, Dale A.; Krishnasamy, Vikram; Barr, John R.; Thomas, Jerry; Pirkle, James L.

doi:10.1056/nejmoa1916433

Cited by 582 publications

(610 citation statements)

References 20 publications

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“…This is important to consider given the documented but rare cases of cannabis acquired aspergillosis fatalities while human exclusive THCA toxicity has never been conclusively documented (McKernan et al 2015; McKernan et al 2016; McKernan 2018b). While, the recent vaporizer fatalities are associated with THCA products, these toxicities are not attributed to the therapeutic index of THC but to the solvents (Vitamin E acetate) often used in the clandestine manufacturing practices(Blount et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes

McKernan

Helbert

Kane

et al. 2020

Preprint

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Cannabis is a diverse and polymorphic species. To better understand cannabinoid synthesis inheritance and its impact on pathogen resistance, we shotgun sequenced and assembled a Cannabis trio (sibling pair and their offspring) utilizing long read single molecule sequencing. This resulted in the most contiguous Cannabis sativa assemblies to date. These reference assemblies were further annotated with full-length male and female mRNA sequencing (Iso-Seq) to help inform isoform complexity, gene model predictions and identification of the Y chromosome. To further annotate the genetic diversity in the species, 40 male, female, and monoecious cannabis and hemp varietals were evaluated for copy number variation (CNV) and RNA expression. This identified multiple CNVs governing cannabinoid expression and 82 genes associated with resistance to Golovinomyces chicoracearum, the causal agent of powdery mildew in cannabis. Results indicated that breeding for plants with low tetrahydrocannabinolic acid (THCA) concentrations may result in deletion of pathogen resistance genes. Low THCA cultivars also have a polymorphism every 51 bases while dispensary grade high THCA cannabis exhibited a variant every 73 bases. A refined genetic map of the variation in cannabis can guide more stable and directed breeding efforts for desired chemotypes and pathogen-resistant cultivars. Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes

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Section: Discussionmentioning

confidence: 99%

Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes

McKernan

Helbert

Kane

et al. 2020

Preprint

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“…The presence of harmful compounds, such as MCT oil, VEA, and other lipids in THC-containing cartridges has been identified by the FDA/CDC (Blount et al 2019a). At present, VEA has been linked as the causative agent based on bronchoalveolar lavage fluid (BALF) analyses in patients with EVALI (Blount et al 2019b). Thus far, the EVALI epidemic has only been seen in North American populations, with very few cases reported in Canada (Stanbrook 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Counterfeit street cartridges are produced by using cutting agents, such as medium-chain triglyceride (MCT) oil, vitamin E (tocopherol) acetate (VEA), and seized drugs, such as butane hash oil (Layden et al 2019). Currently, vitamin E acetate (VEA) has been identified as a key agent involved in EVALI (Blount et al 2019b). However, VEA would not impose chemical-induced pneumonia, as VEA is protective in the lung upon aerosolization (Hybertson et al ; Wang et al).…”

Section: Introductionmentioning

confidence: 99%

Chemical constituents involved in e-cigarette, or vaping product use-associated lung injury (EVALI)

Muthumalage

Friedman

McGraw

et al. 2020

Preprint

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AbstractBackgroundThe Centers for Disease Control (CDC) declared e-cigarette (e-cig), or vaping product use-associated lung injury (EVALI) a national outbreak due to the high incidence of emergency department admissions and deaths. Investigators have identified vitamin E acetate (VEA) as the plausible cause for EVALI, based on compounds found in bronchoalveolar lavage fluid.ObjectivesWe defined the chemical constituents present in e-cig cartridges associated with EVALI and compared constituents to medical-grade and cannabidiol (CBD) containing cartridges.MethodsWe measured chemicals and elemental metals in e-liquid and vapor phases of e-cig counterfeit cartridges by Gas Chromatography (GC) and Mass Spectrometry (MS), EPA method TO-15 by GCMS, and ICP-MS analysis.ResultsWe have identified chemical constituents in e-cig vaping tetrahydrocannabinol (THC)-containing counterfeit cartridges compared to medical-grade and cannabidiol (CBD) containing cartridges. Apart from VEA and THC, other potential toxicants correlated with EVALI included solvent-derived hydrocarbons, silicon conjugated compounds, various terpenes, pesticides/plasticizers/polycaprolactones, and metals. These chemicals are known to cause symptoms, such as cough, shortness of breath or chest pain, nausea, vomiting or diarrhea, fatigue, fever, or weight loss, all symptoms presenting in patients with EVALI.ConclusionThis study provides insights into understanding the chemical-induced disease mechanism of acute lung injury.

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“…The testing was limited due to the quantity of remaining product. As such, we prioritized the analysis to pesticides while also evaluating for the vitamin E which had been found in recent cases [10]. Using previously validated methods at the Iowa State Hygienic Laboratory, bifenazate (13 ppm), boscalid (0.14 ppm), and tebuconazole (0.73 ppm) were detected quantitatively (via liquid chromatography-tandem mass spectrometry [LC-MS/MS]), and cannabinoids and vitamin E acetate were detected qualitatively (via gas chromatographymass spectrometry).…”

Section: Laboratory Analysis Of Vaping Devicementioning

confidence: 99%

“…We will defer discussion of aflatoxin and cannabinoids as these are not known to cause acute tissue damage and their effects are well described. Furthermore, we will defer the complex discussion on vitamin E acetate because it was discussed in other publications and is under investigation by the United States Food and Drug Administration [8,10]. The following pesticides were not detected at the level of quantification (LOQ) of 0.065 ppm via LC-MS/MS: acetamiprid, aldicarb, azoxystrobin, carbaryl, carbofuran, chlorantraniliprole, fipronil, flonicamid, imidacloprid, metalaxyl, methiocarb, methomyl, thiacloprid, and thiamethoxam.…”

Section: Laboratory Analysis Of Vaping Devicementioning

confidence: 99%

E-Cigarette, or Vaping, Product Use Associated Lung Injury (EVALI) with Acute Respiratory Failure in Three Adolescent Patients: a Clinical Timeline, Treatment, and Product Analysis

et al. 2020

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Introduction E-cigarette, or vaping, product use associated lung injury (EVALI) has become a recent concern among public health officials. Factors that contribute to the concern include an increasing number of cases over time, the severity of the illness, and an unknown understanding of the pathophysiology and etiology of the illness. Case Series We cared for three adolescent patients with acute respiratory failure secondary to EVALI. All three patients were treated with high-dose steroids in addition to antimicrobials, which resulted in clinical improvement and resolution of their respiratory failure. Pulmonary function testing was performed on these previously healthy patients both acutely and subacutely. Additionally, we report the results from the laboratory analysis of one vaping device fluid which revealed previously unpublished components within these products. Discussion EVALI is a recent public health concern without a known etiology which can cause life-threatening lung injury in patients without prior lung pathology. We hope these cases will highlight the importance of return precautions in adolescents with vague respiratory symptoms and provide a cautionary tale to providers while they counsel patients regarding the use of these products.

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Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

Cited by 582 publications

References 20 publications

Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes

Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes

Chemical constituents involved in e-cigarette, or vaping product use-associated lung injury (EVALI)

E-Cigarette, or Vaping, Product Use Associated Lung Injury (EVALI) with Acute Respiratory Failure in Three Adolescent Patients: a Clinical Timeline, Treatment, and Product Analysis

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