Since August 2019, CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders have been investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). This report updates patient demographic characteristics, self-reported substance use, and hospitalization dates for EVALI patients reported to CDC by states, as well as the distribution of emergency department (ED) visits related to e-cigarette, or vaping, products analyzed through the National Syndromic Surveillance Program (NSSP). As of January 14, 2020, a total of 2,668 hospitalized EVALI cases had been reported to CDC. Median patient age was 24 years, and 66% were male. Overall, 82% of EVALI patients reported using any tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product (including 33% with exclusive THC-containing product use), and 57% of EVALI patients reported using any nicotine-containing product (including 14% with exclusive nicotine-containing product use). Syndromic surveillance indicates that ED visits related to e-cigarette, or vaping, products continue to decline after sharply increasing in August 2019 and peaking in September 2019. Clinicians and public health practitioners should remain vigilant for new EVALI cases. CDC recommends that persons not use THC-containing e-cigarette, or vaping, products, especially those acquired from informal sources such as friends, family members, or from in-person or online dealers. Vitamin E acetate is strongly linked to the EVALI outbreak and should not be added to any e-cigarette, or vaping, products (2). However, evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC- or non-THC-containing products, in some reported EVALI cases.

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Update: Characteristics of a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, August 2019-January 2020.

Importance Tobacco use is the leading preventable cause of disease, disability, and death in the US In 2014, it was estimated that 480 000 deaths annually are attributed to cigarette smoking, including second hand smoke exposure Smoking during pregnancy can increase the risk of numerous adverse pregnancy outcomes (eg, miscarriage and congenital anomalies) and complications in the offspring (including sudden infant death syndrome and impaired lung function in childhood) In 2019, an estimated 506 million US adults (208% of the adult population) used tobacco; 140% of the US adult population currently smoked cigarettes and 45% of the adult population used electronic cigarettes (e-cigarettes) Among pregnant US women who gave birth in 2016, 72% reported smoking cigarettes while pregnant Objective To update its 2015 recommendation, the USPSTF commissioned a review to evaluate the benefits and harms of primary care interventions on tobacco use cessation in adults, including pregnant persons Population This recommendation statement applies to adults 18 years or older, including pregnant persons Evidence assessment The USPSTF concludes with high certainty that the net benefit of behavioral interventions and US Food and Drug Associated (FDA)-approved pharmacotherapy for tobacco smoking cessation, alone or combined, in nonpregnant adults who smoke is substantial The USPSTF concludes with high certainty that the net benefit of behavioral interventions for tobacco smoking cessation on perinatal outcomes and smoking cessation in pregnant persons is substantial The USPSTF concludes that the evidence on pharmacotherapy interventions for tobacco smoking cessation in pregnant persons is insufficient because few studies are available, and the balance of benefits and harms cannot be determined The USPSTF concludes that the evidence on the use of e-cigarettes for tobacco smoking cessation in adults, including pregnant persons, is insufficient, and the balance of benefits and harms cannot be determined The USPSTF has identified the lack of well-designed, randomized clinical trials on e-cigarettes that report smoking abstinence or adverse events as a critical gap in the evidence Recommendations The USPSTF recommends that clinicians ask all adults about tobacco use, advise them to stop using tobacco, and provide behavioral interventions and FDA-approved pharmacotherapy for cessation to nonpregnant adults who use tobacco (A recommendation) The USPSTF recommends that clinicians ask all pregnant persons about tobacco use, advise them to stop using tobacco, and provide behavioral interventions for cessation to pregnant persons who use tobacco (A recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of pharmacotherapy interventions for tobacco cessation in pregnant persons (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of e-cigarettes for tobacco cessation in adults, including pregnant persons The USPSTF recommends that clinicians direct patients who use tobacco to other tobacco cessation interventions with proven effectiveness and established safety (I statement)

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Interventions for Tobacco Smoking Cessation in Adults, Including Pregnant Persons: US Preventive Services Task Force Recommendation Statement

An Animal Model of EVALI In this study, investigators developed a mouse model of e-cigarette, or vaping, product use–associated lung injury. They showed that in these mice, vitamin E acetate induce...

https://www.nejm.org/doi/pdf/10.1056/NEJMc2000231?articleTools=true

An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury.

https://escholarship.org/content/qt62f3w0zd/qt62f3w0zd.pdf?t=qlqirh

Dexamethasone in hospitalised patients with COVID-19: addressing uncertainties.

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 long-term 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 inform of the danger are now required, as public perception has grown that vaping is not harmful.

https://www.pnas.org/content/pnas/117/12/6349.full.pdf

Potential for release of pulmonary toxic ketene from vaping pyrolysis of vitamin E acetate.

Background 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 tox...

/pdf/vitamin-e-acetate-in-bronchoalveolar-lavage-fluid-associated-9pia6yx70u.pdf

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) with stable isotope labeled internal standards (SIL-IS) is the gold standard for quantitative analysis of drugs and metabolites in complex biological samples. Significant isotopic effects associated with deuterium labeling often causes the deuterated IS to elute at a different retention time from the target analyte, diminishing its capability to compensate for matrix effects. In this study, we systematically compared the analytical performance of deuterated (2H) SIL-IS to non-deuterated (13C and 15N) SIL-ISs for quantifying urinary 2-methylhippuric acid (2MHA) and 4-methylhippuric acid (4MHA), biomarkers of xylenes exposure, with an LC-ESI-MS/MS assay. Analytical method comparison between IS demonstrated a quantitative bias for urinary 2MHA results, with concentrations generated with 2MHA-[2H7] on average 59.2% lower than concentrations generated by 2MHA-[13C6]. Spike accuracy, measured by quantifying analyte-spiked urine matrix and comparing the result to the known spike concentration, determined that 2MHA-[2H7] generated negatively biased urinary results of -38.4% whereas no significant bias was observed for 2MHA-[13C6]. Post-column infusion demonstrated that ion suppression experienced by 2MHA and 2MHA-[13C6] was not equally experienced by 2MHA-[2H7], explaining the negatively biased 2MHA results. Quantitation of urinary 4MHA results between IS exhibited no significant quantitative bias. These results underscore the importance of careful selection of internal standards for targeted quantitative analysis in complex biological samples.

Chris Reese

Papers

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

Mitigating Matrix Effects in LC-ESI-MS/MS Analysis of a Urinary Biomarker of Xylenes Exposure.