Nicotine vaping was not the cause of e‐cigarette, or vaping, product use‐associated lung injury in the United States

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.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders continue to investigate a nationwide outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI) ( 1 ). This report updates demographic and self-reported product-use and substance-use characteristics of hospitalized EVALI patients reported to CDC from available interview or medical record abstraction data. As of December 3, 2019, all 50 states, the District of Columbia (DC), and two U.S. territories (Puerto Rico and U.S. Virgin Islands) reported 2,291 patients hospitalized with EVALI. A total of 48 (2% of total reported cases) deaths occurred in 25 states and DC. Median patient age was 24 years, 67% were male, and the largest number of weekly hospitalized cases occurred during the week of September 15, 2019; weekly hospitalized cases since then have steadily declined. Among all hospitalized EVALI patients reported to CDC weekly, the percentage of recent cases (patients hospitalized within the preceding 3 weeks) declined from 58% reported November 12 to 30% reported December 3. Overall, 80% of hospitalized EVALI patients reported using tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, products. “Dank Vapes,” a class of largely counterfeit THC-containing products of unknown origin, were the most commonly reported THC-containing branded products nationwide and among all major U.S. Census regions. However, regional differences in THC-containing product use were noted; TKO and Smart Cart brands were more commonly reported by patients in the West region compared with other regions. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. The nationwide diversity of THC-containing products reported by patients suggests it is unlikely a single brand is responsible for the EVALI outbreak, and regional differences in THC-containing products might be related to product sources. Although it appears that vitamin E acetate is associated with EVALI, many substances and product sources are being investigated, and there might be more than one cause. Therefore, while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products. CDC has worked with state health departments and a task force formed by the Council of State and Territorial Epidemiologists to develop and disseminate surveillance case definitions* and data collection tools † to monitor and track cases beginning in August 2019. States and jurisdictions voluntarily report the number of confirmed and probable hospitalized EVALI cases and all EVALI-associated deaths to CDC on a weekly basis. This report is limited to data on hospitalized EVALI patients and all EVALI-associated deaths reported to CDC as of December 3, 2019 ( 2 ), and updates patient demographic characteristics, the number and diversity of self-reported substances, and brands used in e-cigarette, or vaping, products. Distribution of THC-containing brands is reported nationally and by U.S. Census region. § 2018 U.S. Census population estimates were used to calculate rates (hospitalized EVALI cases per 1 million population) by state. ¶ Because of the time required to investigate cases, weekly reports to CDC include recent EVALI cases (patients hospitalized within the preceding 3 weeks) and past EVALI cases (those hospitalized earlier). To assess the recent trajectory of the EVALI outbreak, this report examined the percentage of all hospitalized EVALI patients reported weekly who had been hospitalized within the preceding 3 weeks. As of December 3, 2019, all 50 states, DC, Puerto Rico, and the U.S. Virgin Islands reported 2,291 hospitalized EVALI cases to CDC (Table). Overall, a total of 48 (2% of total reported cases) EVALI-associated deaths occurred in 25 states and DC, which include one nonhospitalized case and two cases with unknown hospitalization status. Among hospitalized EVALI patients for whom data were available, 67% were male, and the median age was 24 years (range = 13–77 years); 78% of patients were aged 60% of hospitalized EVALI patients in the Northeast and South regions. Regional differences were seen in reported use of many products, including Smart Cart, which was reportedly used by a higher proportion of hospitalized EVALI patients in the West (24%) compared with those in the South (14%), Midwest (14%) and Northeast (6%). TKO was reported by more than twice as many hospitalized EVALI patients in the West (29%) as in the Northeast (14%), Midwest (12%), and South (2%) regions. FIGURE 3 Percentage of hospitalized EVALI patients (N = 482) who reported brand names of THC-containing e-cigarettes, or vaping, products,* by U.S. Census region † — United States, August–December 2019 Abbreviations: EVALI = e-cigarette, or vaping, product use–associated lung injury; THC = tetrahydrocannabinol. * “Other products” included 146 unique products. Dabwood and Brass Knuckles were reported by 10% of patients in the Northeast and West regions. Off White, Moon Rocks, Chronic Carts, Mario Carts, Cereal Carts, Runtz, Dr. Zodiac, Eureka, Supreme G, and CaliPlug were reported by 1%–5% of patients nationwide. Use of 134 other products were reported by <1% of hospitalized patients. † Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont. Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin. South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia. West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming. Puerto Rico and U.S. Virgin Islands were included in the South region. The figure is a bar chart showing the percentage of hospitalized EVALI patients who reported brand names of THC-containing e-cigarettes, or vaping, products, by U.S. Census region during August–December 2019. Discussion This report updates the characteristics of hospitalized EVALI patients, as well as those who died, and provides the first national data on the number and diversity of THC-containing products used. Among hospitalized EVALI patients as of December 3, 2019, the age, sex, and race distributions were similar to those reported previously ( 1 – 3 ), with a predominance of patients being young adults, male, and white. The persistent decline in number of cases reported each week since mid-September, coupled with the declining percentage of recent cases reported, suggest that the outbreak may have peaked around September 15. However, states continue to report new cases, including deaths, to CDC on a weekly basis. Therefore, this investigation remains ongoing, and it is important for states to remain vigilant with EVALI case finding and reporting. THC-containing products continue to be the most commonly reported e-cigarette, or vaping, products used by hospitalized EVALI patients; 80% reported any use of these products in the 3 months preceding symptom onset. Dank Vapes were the most commonly reported THC-containing branded product reported nationally, as well as by U.S. Census region, which is consistent with data reported in October from Illinois and Wisconsin ( 4 ). Dank Vapes are a class of largely counterfeit THC-containing products and have been associated with EVALI ( 4 , 5 ). However, regional differences in THC-containing product use were identified. The nationwide diversity of THC-containing products reported by EVALI patients highlights that it is not likely a single brand that is responsible for the EVALI outbreak, and that regional differences in THC-containing products might be related to product sources. The finding that most EVALI patients reported use of THC-containing products, in particular use of counterfeit branded products such as Dank Vapes, is important given recent findings from Minnesota that showed THC-containing products obtained from EVALI patients and counterfeit products seized in the state contained vitamin E acetate ( 6 ). Prior testing of bronchoalveolar lavage fluid samples implicated Vitamin E acetate as a chemical of concern in the outbreak after it was found in all assessed specimens from 29 EVALI patients ( 7 ). Additionally, FDA product testing identified vitamin E acetate in THC-containing products obtained from EVALI patients; among 545 THC-containing products collected from 70 EVALI patients, 79% of the 70 EVALI patients provided at least one THC-containing product, and among those, 76% provided at least one product containing vitamin E acetate.** However, given that a small but consistent number of EVALI patients report exclusive use of nicotine-containing (13%) or CBD-containing (1%) products ( 1 , 2 ), additional product and biologic testing from EVALI patients with these use patterns is warranted. Further research is being conducted by CDC and others to compare biologic specimens from EVALI patients with those from nonpatients who use e-cigarette, or vaping, products and to explore possible pathophysiologic mechanisms through which vitamin E acetate might cause lung injury. The findings in this report are subject to at least five limitations. First, data on substances used in e-cigarette, or vaping, products were self-reported or reported by proxies (e.g., family members) and might be subject to recall or social desirability bias. Second, data related to product use were missing for many patients, and conclusions derived from these data might not be generalizable to the entire affected population. Third, many EVALI patients were not interviewed because of loss to follow-up, refusal to be interviewed, or lack of resources to conduct interviews, which might limit the generalizability of these findings to other EVALI patients. Fourth, reporting lags make it difficult to evaluate the trajectory of the outbreak during recent weeks. Finally, these data might be subject to misclassification of substance use for multiple reasons. Patients might not know the content of the e-cigarette, or vaping, products they used, and methods used to collect data regarding substance use varied across jurisdictions. CDC is working with state and federal partners (e.g., FDA) to link epidemiologic, product, and biologic samples to further explore the complexities of the EVALI outbreak. Based on findings to date, CDC recommends that persons not use e-cigarette, or vaping, products that contain THC, especially those acquired from informal sources like friends, family members, or in-person or online dealers. In addition, persons should not add any other substances to products not intended by the manufacturer, including products purchased through retail establishments. Vitamin E acetate should not be added to e-cigarette, or vaping, products. However, although it appears that vitamin E acetate is associated with EVALI, many substances and product sources are being investigated, and there might be more than one cause. Therefore, while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products. Adults using e-cigarette, or vaping, products to quit smoking should not return to smoking cigarettes; they should weigh all risks and benefits and consider using FDA-approved cessation medications. †† Adults who continue to use e-cigarette, or vaping, products should carefully monitor themselves for symptoms and see a health care provider immediately if they develop symptoms similar to those reported in this outbreak ( 8 ). Irrespective of the ongoing investigation, e-cigarette, or vaping, products should never be used by youths, young adults, or pregnant women. Summary What is already known about this topic? Patients with e-cigarette, or vaping, product use–associated lung injury (EVALI) in Illinois and Wisconsin reported using a variety of tetrahydrocannabinol (THC)-containing products in the 3 months preceding illness; a product labeled “Dank Vapes” was most commonly reported. What is added by this report? Nationally, Dank Vapes were the most commonly reported THC-containing product by hospitalized EVALI patients, but a wide variety of products were reported, with regional differences. Data suggest the outbreak might have peaked in mid-September. What are the implications for public health practice? These data further support the association of EVALI with THC-containing products; it is unlikely that one brand is responsible for the outbreak. CDC recommends that persons not use e-cigarette, or vaping, products that contain THC.