Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

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Abstract

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.

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Fatty Acids Composition of Vegetable Oils and Its Contribution to Dietary Energy Intake and Dependence of Cardiovascular Mortality on Dietary Intake of Fatty Acids

Jana Orsavova, Ladislava Misurcova, Jarmila Vavra Ambrozova … (2015)

Characterizations of fatty acids composition in % of total methylester of fatty acids (FAMEs) of fourteen vegetable oils—safflower, grape, silybum marianum, hemp, sunflower, wheat germ, pumpkin seed, sesame, rice bran, almond, rapeseed, peanut, olive, and coconut oil—were obtained by using gas chromatography (GC). Saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), palmitic acid (C16:0; 4.6%–20.0%), oleic acid (C18:1; 6.2%–71.1%) and linoleic acid (C18:2; 1.6%–79%), respectively, were found predominant. The nutritional aspect of analyzed oils was evaluated by determination of the energy contribution of SFAs (19.4%–695.7% ERDI), PUFAs (10.6%–786.8% ERDI), n-3 FAs (4.4%–117.1% ERDI) and n-6 FAs (1.8%–959.2% ERDI), expressed in % ERDI of 1 g oil to energy recommended dietary intakes (ERDI) for total fat (ERDI—37.7 kJ/g). The significant relationship between the reported data of total fat, SFAs, MUFAs and PUFAs intakes (% ERDI) for adults and mortality caused by coronary heart diseases (CHD) and cardiovascular diseases (CVD) in twelve countries has not been confirmed by Spearman’s correlations.

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Current perspectives in pulmonary surfactant--inhibition, enhancement and evaluation.

Yi Y Zuo, Ruud Veldhuizen, A Neumann … (2008)

Pulmonary surfactant (PS) is a complicated mixture of approximately 90% lipids and 10% proteins. It plays an important role in maintaining normal respiratory mechanics by reducing alveolar surface tension to near-zero values. Supplementing exogenous surfactant to newborns suffering from respiratory distress syndrome (RDS), a leading cause of perinatal mortality, has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but with only limited success. Biophysical studies suggest that surfactant inhibition is partially responsible for this unsatisfactory performance. This paper reviews the biophysical properties of functional and dysfunctional PS. The biophysical properties of PS are further limited to surface activity, i.e., properties related to highly dynamic and very low surface tensions. Three main perspectives are reviewed. (1) How does PS permit both rapid adsorption and the ability to reach very low surface tensions? (2) How is PS inactivated by different inhibitory substances and how can this inhibition be counteracted? A recent research focus of using water-soluble polymers as additives to enhance the surface activity of clinical PS and to overcome inhibition is extensively discussed. (3) Which in vivo, in situ, and in vitro methods are available for evaluating the surface activity of PS and what are their relative merits? A better understanding of the biophysical properties of functional and dysfunctional PS is important for the further development of surfactant therapy, especially for its potential application in ARDS.

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Evaluation of Bronchoalveolar Lavage Fluid from Patients in an Outbreak of E-cigarette, or Vaping, Product Use–Associated Lung Injury — 10 States, August–October 2019

Benjamin Blount, Mateusz P Karwowski, Maria Morel-Espinosa … (2019)

CDC, the Food and Drug Administration (FDA), state and local health departments, and multiple public health and clinical partners are investigating a national outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI). Based on data collected as of October 15, 2019, 86% of 867 EVALI patients reported using tetrahydrocannabinol (THC)-containing products in the 3 months preceding symptom onset ( 1 ). Analyses of THC-containing product samples by FDA and state public health laboratories have identified potentially harmful constituents in these products, such as vitamin E acetate, medium chain triglyceride oil (MCT oil), and other lipids ( 2 , 3 ) (personal communication, D.T. Heitkemper, FDA Forensic Chemistry Center, November 2019). Vitamin E acetate, in particular, might be used as an additive in the production of e-cigarette, or vaping, products; it also can be used as a thickening agent in THC products ( 4 ). Inhalation of vitamin E acetate might impair lung function ( 5 – 7 ). Bronchoscopy and bronchoalveolar lavage † (BAL) can be part of the clinical and diagnostic workup of EVALI patients. The decision to perform this procedure is made by the clinical team on a case-by-case basis ( 8 ). During August–October 2019, BAL fluid specimens were collected by clinical teams caring for hospitalized EVALI patients. Public health laboratories and health departments from 10 states (California, Connecticut, Hawaii, Illinois, Maryland, Michigan, Minnesota, Texas, Utah, and Wisconsin) coordinated the submission of residual BAL fluid specimens from 29 patients to CDC. To better characterize exposure among EVALI patients, CDC developed and validated isotope dilution mass spectrometry methods to analyze specific toxicants of concern and active compounds in case-associated BAL fluid. § These CDC analytic methods can identify vitamin E acetate, MCT oil (medium chain triglycerides), plant oils (long chain triglycerides), petroleum distillates (including mineral oil), diluent terpenes, cannabinoids, and nicotine in BAL fluid. The quality of case-associated BAL specimens was assessed by measuring dipalmitoylphosphatidylcholine (DPPC), the principal phospholipid in naturally-occurring lung surfactant: the presence of acceptable levels of DPPC confirms that the lavage procedure recovered adequate pulmonary epithelial fluid. When specimen volume was insufficient to perform all planned analyses, analysis of vitamin E acetate and cannabinoids was prioritized. Among the 27 BAL fluid specimens with sufficient volume for testing, all had measurable levels of DPPC. Overall, 21 (72%) patients with available specimens were male, and their median age was 23 years (range = 16–67 years), which is consistent with the sex and age patterns of EVALI patients reported to CDC to date ( 1 ). Two of the patients died. Vitamin E acetate was detected in all 29 patient BAL samples. Among 23 patients for whom self-reported THC use information was available, 20 reported using THC-containing products. THC or its metabolites were detected in 23 of 28 patient BAL samples, including in those of three patients who said they did not use THC products. Nicotine metabolites were detected in 16 of 26 patient BAL specimens. Results for plant oils, MCT oil, petroleum distillates, and diluent terpenes were all below analyte-specific levels of detection (typically in the low ng/mL range). This is the first reported identification of a potential toxicant of concern (vitamin E acetate) in biologic specimens obtained from EVALI patients. These findings provide direct evidence of vitamin E acetate at the primary site of injury among EVALI patients and are consistent with FDA product testing and media reports of state public health laboratory testing documenting vitamin E acetate in product samples used by EVALI patients ( 2 , 3 ) (Personal communication, D.T. Heitkemper, FDA Forensic Chemistry Center, November 2019). Other diluents and additives of concern (e.g., plant oils, MCT oil, petroleum distillates, and diluent terpenes) were notably not detected in BAL fluid specimens from EVALI patients. Although vitamin E acetate was detected in all specimens in this analysis of a convenience sample of 29 EVALI case-associated BAL specimens, additional studies are needed, including comparison with BAL fluid specimens from healthy volunteers and animal studies using controlled exposures to establish whether a causal link exists between this exposure and EVALI. Based on these data from 29 patients, it appears that vitamin E acetate is associated with EVALI; however, it is possible that more than one compound or ingredient could be a cause of lung injury, and evidence is not yet sufficient to rule out contribution of other toxicants to EVALI. These findings reinforce CDC’s recommendation that persons should not use e-cigarette, or vaping, products containing THC, especially those obtained from informal sources such as friends or family, or those from the illicit market, where product ingredients are unknown or can be highly variable ( 9 ). Until the relationship of vitamin E acetate and lung health is better characterized, it is important that vitamin E acetate not be added to e-cigarette, or vaping, products. CDC will continue to update guidance, as appropriate, as new data become available from this outbreak investigation.

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Journal

Title: New England Journal of Medicine

Abbreviated Title: N Engl J Med

Publisher: Massachusetts Medical Society

ISSN (Print): 0028-4793

ISSN (Electronic): 1533-4406

Publication date (Electronic): December 20 2019

Affiliations

[1 ]From the Division of Laboratory Sciences, National Center for Environmental Health (B.C.B., M.P.K., M.M.-E., L.V.-B., M.G., M.B., C.R.B., K.T.C., D.C., J.C., E.C., V.R.D.J., P.E., C.F., C.H., Z.K., J.D.K., C.N., G.B.R., J.R., C.R., L.S., T.S., C.S., D.T., L.W., C.W., B.X., J.R.B., J.T., J.L.P.), Epidemic Intelligence Service, Center for Surveillance, Epidemiology, and Laboratory Sciences (I.G.), the Office of the Director (P.B.) and the Office on Smoking and Health (B.A.K.), National Center for Chronic...

Article

DOI: 10.1056/NEJMoa1916433

PMC ID: 7032996

PubMed ID: 31860793

SO-VID: 16eabe5e-9384-4f39-a27f-aab368b2b341

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Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

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Most cited references 18

Fatty Acids Composition of Vegetable Oils and Its Contribution to Dietary Energy Intake and Dependence of Cardiovascular Mortality on Dietary Intake of Fatty Acids

Current perspectives in pulmonary surfactant--inhibition, enhancement and evaluation.

Evaluation of Bronchoalveolar Lavage Fluid from Patients in an Outbreak of E-cigarette, or Vaping, Product Use–Associated Lung Injury — 10 States, August–October 2019

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