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CDC Studying Tissue To Try And Track Down Root Cause Of Vaping-Related Lung Damage October 22, 20194:21 PM ET Heard on All Things Considered RICHARD HARRIS The Centers for Disease Control and Prevention is starting to study lung tissue and chemicals from electronic cigarette vapor to track down the root cause of lung damage caused by vaping. https://www.npr.org/2019/10/22/772368792/cdc-studying-tissue-to-try-and-track-down-root-cause-of-vaping-related-lung-dama

The Centers for Disease Control and Prevention is starting to study lung tissue and chemicals from electronic cigarette vapor to track down the root cause of lung damage caused by vaping. https://www.npr.org/2019/10/22/772368792/cdc-studying-tissue-to-try-and-track-down-root-cause-of-vaping-related-lung-dama

Lung Injury Associated with Vaping – Oct. 22, 2019 DSHS has identified 147 Texas cases of severe lung disease in people who report vaping before developing symptoms, including one death. State health officials are gathering more information about 17 other possible cases to determine whether they are consistent with the symptoms and substance use seen in cases in Texas and 48 other states. Patients range in age from 13 to 75 years old, with a median age of 22 years. About one-quarter of the people affected in Texas are minors. Three-quarters are male, and nine in ten report vaping THC or marijuana, possibly in conjunction with other substances. Almost all were hospitalized with many requiring intensive care. Respiratory symptoms include difficulty breathing, shortness of breath and coughing. Some people have also experienced nausea, vomiting and diarrhea. Clinicians should ask patients with these symptoms about a history of vaping, gather as much information as possible about suspected cases, and report them to DSHS. Nationally, 1,479 cases have been reported, and DSHS is working with the Centers of Disease Control and Prevention, the Food and Drug Administration and other states to gather evidence about what the cases have in common and determine a cause. Until we know more about the cause, people should consider not using e-cigarettes. If you do vape and experience symptoms like those reported, seek medical care promptly. Regardless of the ongoing situation: Youth and young adults should not vape. Women who are pregnant should not vape. Adults who do not currently use tobacco products should not start vaping. Case counts will be updated each Tuesday. News Release Updated Health Alert Latest Information from CDC Lung Injury Associated with Vaping, Texas Public Health Region Number of Cases 1 (Panhandle) 2 2/3 (North Texas) 75 4/5N (East Texas) 4 6/5S (Southeast Texas) 34 7 (Central Texas) 14 8 (South Texas) 6 9/10 (West Texas) 3 11 (Rio Grande Valley) 8 Not yet determined 1 Total 147 Figure 1: Cases of Lung Injury Associated with Vaping, Texas, as of 10/22/19 https://www.dshs.texas.gov/news/updates.shtm#vaping

Mississippi Cases Last updated October 22, 2019. Outbreak Cases 7 Since September 17, 2019 Hospitalized 6 (86%) Deaths 1 Case Statistics Sex Male: 5 (71%); Female: 2 (29%) Age range Under 18 years: 0 18–34 years: 7 35+ years: 0 Product usage Reported exclusive use of THC-containing/CBD-containing products: 3 (43%) Reported using both nicotine-containing and THC-containing/CBD-containing products: 1 (14%) Reported exclusive use of nicotine-containing products: 3 (43%) Healthcare providers: Report suspected cases to MSDH at 601-576-7725 or 601-576-7400 after hours, weekends and holidays. https://msdh.ms.gov/msdhsite/_static/14,0,418.html

Information updated as of 2:00 pm October 22, 2019 Number of cases: 39 Age range: 15-65 years (median age: 21 years) Gender: 15 Female, 24 Male (62% Male) Number of hospitalizations: 35 (92%) Number of deaths: 0 Counties: Butler, Cuyahoga (7), Fairfield, Franklin (6), Greene, Hamilton (2), Jefferson, Lucas, Mahoning, Medina (2), Miami (2), Montgomery, Portage, Richland (2), Seneca, Summit (4), Tuscarawas, Union (2), Warren, Wayne Additional illness reports under investigation: 30 https://odh.ohio.gov/wps/portal/gov/odh/know-our-programs/tobacco-use-prevention-and-cessation/news-and-events/

Updated October 22, 2019 In Oregon, 12 cases have been reported, 2 of which resulted in death. https://www.oregon.gov/oha/PH/DISEASESCONDITIONS/COMMUNICABLEDISEASE/Pages/vaping-illness.aspx

Vaping-associated Illness* Data Lable Value Confirmed and Probable Cases Total Confirmed 23 Total Probable 22 Deaths 1** Most Recent 10/9/2019 Age Range 15-70 Median Age 21 Gender 14 female, 31 male Regions of State Impacted Statewide Reports Under Investigation Total 38 Most Recent 10/18/2019 Age Range 14-63 Median Age 21 Gender 12 female, 26 male Regions of State Impacted North, Central *Chart Updated Every Tuesday **Part of Probable Cases https://www.nj.gov/health/fhs/tobacco/vaping/index.shtml

Lung Injury Associated with E-Cigarette Use, or Vaping* - Florida Year Reported Cases Year-to-Date Deaths Year-to-Date 2019 70 1 Report last updated on October 22, 2019 with data from January 01, 2019 - October 19, 2019. FLHealthCharts.com is provided by the Florida Department of Health, Division of Public Health Statistics & Performance Management. Data Source: Florida Department of Health, Division of Disease Control and Health Protection, Florida Bureau of Epidemiology. Data Note(s) The counts here represent the cases of Lung Injury Associated with E-Cigarette Use, or Vaping reported into Florida's reportable disease surveillance system, Merlin. Legal authority: Pursuant to section 381.0031(6), Florida Statutes, and Rule 64D- 3.041, Florida Administrative Code, the Department and its authorized representatives, when deemed necessary to protect the public’s health, may conduct epidemiological investigations and follow-up to confirm the diagnosis, treatment and causes of any disease or condition to determine appropriate methods of outbreak and communicable disease control. * Includes vaping using an electronic device (e.g., electronic nicotine delivery system (ENDS), electronic cigarette, e-cigarette, vaporizer, vape(s), vape pen, dab pen, or other) to inhale substances (e.g., nicotine, marijuana, THC, THC concentrates, CBD, synthetic cannabinoids, flavorings, or other substances), with or without smoking of any plant, chemical, or substance. http://www.flhealthcharts.com/ChartsReports/rdPage.aspx?rdReport=ChartsProfiles.LungInjuryE-CigaretteUse

References Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin—preliminary report. New Engl J Med 2019. Epub September 6, 2019. https://www.nejm.org/doi/full/10.1056/NEJMoa1911614external icon Perrine CG, Pickens CM, Boehmer TK, et al.; Lung Injury Response Epidemiology/Surveillance Group. Characteristics of a multistate outbreak of lung injury associated with e-cigarette use or vaping—United States, 2019. MMWR Morb Mortal Wkly Rep 2019;68:860–4. CrossRefexternal icon PubMedexternal icon Schier JG, Meiman JG, Layden J, et al.; CDC 2019 Lung Injury Response Group. Severe pulmonary disease associated with electronic-cigarette-product use—interim guidance. MMWR Morb Mortal Wkly Rep 2019;68:787–90. CrossRefexternal icon PubMedexternal icon Lee J, Park J, Go A, et al. Urine multi-drug screening with GC-MS or LC–MS-MS using SALLE-hybrid PPT/SPE. J Anal Toxicol 2019;42:617–24. CrossRefexternal icon PubMedexternal icon Kedzior KK, Laeber LT. A positive association between anxiety disorders and cannabis use or cannabis use disorders in the general population—a meta-analysis of 31 studies. BMC Psychiatry 2014;14:136. CrossRefexternal icon PubMedexternal icon CDC. State Tobacco Activities Tracking and Evaluation (STATE) system. State highlights. Atlanta, GA: US Department of Health and Human Services; CDC; 2019. https://www.cdc.gov/statesystem/statehighlights.html US Census Bureau. 2018 population estimates. Suitland, MD: US Census Bureau; 2019. https://factfinder.census.gov/faces/tableservices/jsf/pages/productview.xhtml?src=bkmkexternal icon Sun L. Vaping lung injuries top 1,000 cases as deaths rise to 18. The Washington Post. October 3, 2019. https://www.washingtonpost.com/health/2019/10/03/vaping-lung-injuries-top-cases-deaths-riseexternal icon Butt YM, Smith ML, Tazelaar HD, et al. Pathology of vaping-associated lung injury. N Engl J Med 2019. Epub October 2, 2019. CrossRefexternal icon PubMedexternal icon CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. Atlanta, GA: US Department of Health and Human Services, CDC; 2019. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html

TABLE 3. Characteristics of tetrahydrocannabinol (THC)- or nicotine-containing products used in the 3 months preceding illness onset in patients with electronic cigarette (e-cigarette), or vaping, product use–associated lung injury (N = 131) — Utah, April–October 2019 Characteristic No. (%) THC-containing products (N = 84) Nicotine-containing products (N = 47) Method of acquisition Friend 37/84 (44) 9/47 (19) Dealer 21/84 (25) 0/47 (0) Online dealer 20/84 (24) 7/47 (15) Out-of-state dispensary 5/84 (6) 1/47 (2) In-state vape shop 1/84 (1) 23/47 (49) Convenience store/gas station 0/84 (0) 7/47 (18) Frequency of use (times per day) <1 8/70 (11) 3/29 (10) 1–5 38/70 (54) 5/29 (17) 6–25 7/70 (10) 5/29 (17) >25 17/70 (24) 16/29 (55) Testing Products tested at UPHL* 19/84 (23) 20/47 (43) Products found to contain THC 19/19 (100) 0/20 (0) Products found to contain nicotine 1/19 (5) 20/20 (100) Products found to contain vitamin E acetate 17/19 (89) 0/20 (0) Abbreviation: UPHL = Utah Public Health Laboratory. * THC-containing cartridges tested came from six patients and nicotine-containing vaping liquids came from eight patients. Test results might therefore represent clusters of purchase or use by these patients rather than fully independent samples.

TABLE 2. Self-reported product use behaviors in the 3 months before injury onset in interviewed patients with electronic cigarette (e-cigarette), or vaping, product use–associated lung injury (N = 53) — Utah, April–October 2019 Product use and behavior No. (%) THC-containing product use Any use 49 (92) Exclusive use 17 (32) THC-containing cartridge brands used Dank Vapes 21 (40) Rove 19 (36) Golden Gorilla 11 (21) Two or more of the above 17 (32) Nicotine-containing product use Any use 35 (66) Exclusive use 3 (6) Both THC- and nicotine-containing product use 32 (60) Abbreviation: THC = tetrahydrocannabinol.

TABLE 1. Characteristics of patients with electronic cigarette (e-cigarette), or vaping, product use–associated lung injury, (N = 83) — Utah, April–October 2019 Characteristic (no. with available information) No. (%) Sex (83) Male 69 (83) Female 14 (17) Age group (yrs) (83) 14–19 11 (13) 20–29 43 (52) 30–39 23 (28) 40–66 6 (7) Required medical care/In-care diagnoses* (79) Hospitalization 70 (89) ICU admission 35 (44) CPAP/BiPAP support (No intubation) 30 (38) Intubation and mechanical ventilation 9 (11) Treated with steroids 59 (75) Acute respiratory distress syndrome 20 (25) Preexisting conditions* (79) Asthma 16 (20) Chronic obstructive pulmonary disease 2 (3) Anxiety 27 (34) Depression 18 (25) Hypertension 4 (5) Heart failure 1 (1) One or more of the above 42 (53) Smoking history*,† (79) Marijuana 34 (43) Tobacco 43 (54) Both marijuana and tobacco 19 (24) Abbreviations: BiPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; ICU = intensive care unit. * Denominators based on total patients with medical abstraction data available (unknowns included in denominator). † Includes current and former smokers.

Discussion In this study of 83 Utah residents with EVALI during August–October 2019, approximately 90% of patients were hospitalized, approximately half in ICUs, and more than half of hospitalized patients required some form of respiratory support. Three quarters were treated with steroids. It is not known why some patients have more severe illness; preexisting behaviors and conditions might play a role in injury exposure, onset, and injury progression. Whereas some patients reported preexisting respiratory problems, most were previously in good physical health, although many reported that they self-identified as current or former smokers of combustible marijuana or tobacco. Many patients reported histories of anxiety or depression, which might influence the use or patterns of e-cigarette, or vaping, product use, particularly products containing THC (5). The median age of patients in this study was 26 years, 3 years older than the national median of 23 years; more than one third were aged ≥30 years. The older age profile in Utah suggests a need to focus on adult populations at risk in addition to younger persons. Utah’s rate of adult e-cigarette use (5.1%) was similar to the national rate (4.6%) in 2017 (the most recent year for which state and national data are available), and e-cigarette use among youths (7.6%) was lower than the national rate (13.2%) in 2017, although rates in all states increased in 2018 and 2019 (6). As of October 15, 2019, Utah’s rate of EVALI was 26 per 1 million compared with four per 1 million nationally (7). More research is needed to identify the constellation of risk factors influencing the high rate of EVALI in Utah. Most patients in this analysis reported using THC-containing products (which are illegal for nonmedical use in Utah) that were sold as prefilled cartridges and obtained from informal sources. Compared with Illinois, Wisconsin, and nationally, patient use rates for prefilled THC-containing cartridges in Utah were even higher while those for nicotine-containing products were lower, reinforcing the finding that unregulated THC-containing cartridges play an important role in this outbreak (1,2). Products labeled with three different brand names, Dank Vapes, Rove, and Golden Gorilla, were each reported by a substantial proportion of patients (20%–40%), although packaging for these brands can be reproduced or purchased online. In Illinois and Wisconsin, Dank Vapes was reported far more than any other brand, Rove was reported by a few patients, and Golden Gorilla was not reported at all (1,2). Although the respective market shares of these brands are unknown, findings from the Utah investigation might reflect a distinct pattern of illicit THC supply and production in Utah or the western United States compared with that in the Midwest and other areas of the United States. Vitamin E acetate was identified in the majority of THC cartridge samples tested at UPHL; however, these samples only represent six patients. National data summarized recently in a news report suggested that vitamin E acetate is a now common diluent in THC cartridges (8). Quantification of vitamin E acetate in Utah’s samples is pending; however, testing of other case samples by the Food and Drug Administration and other laboratories has shown vitamin E acetate concentrations of 31%–88% and lower-than-expected THC concentrations (14%–76% versus the typically advertised 75%–95%) (8). The potential role of vitamin E acetate in lung injury remains unknown; however, the identification of vitamin E acetate among products collected from patients in Utah and elsewhere indicates that the outbreak might be associated with cutting agents or adulterants (9). Ascertaining the potential contribution of diluents to the current outbreak will require data from multiple states and analysis at the national level. The findings in this report are subject to at least five limitations. First, because interviews were not conducted with 30 (36%) patients, nonresponse could introduce selection bias and result in inaccurate estimation of specific substances used and use patterns. Second, because nonmedical THC use currently is illegal in Utah, self-reported use could be influenced by the perceived stigma of illicit substance use or fear of legal repercussions, which might result in underreporting of use. Third, case reporting in Utah relies on clinician reports, which, to date, have come largely from pulmonologists and critical care physicians. Consequently, there is possible reporting bias toward hospitalized patients and those with more severe respiratory symptoms. Fourth, care requirements or preexisting conditions are not always reported on medical charts, meaning that rates could be higher than reported. Finally, because laboratory analysis and coordination are currently limited, there might be factors contributing to the lung injury not yet identified. Effective interventions to halt this outbreak might require a stronger partnership between public health and law enforcement agencies to identify the locations of supply and distribution chains that are contributing to lung injuries, alongside targeted messaging to consumers. UDOH has initiated a print and social media campaign to alert the public to the potential dangers associated with use of THC-containing e-cigarette, or vaping, products. At present, persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific cause or causes of lung injury are not yet known and while the investigation continues, persons should consider refraining from use of all e-cigarette, or vaping, products (10).

In August 2019, the Utah Department of Health (UDOH) received reports from health care providers of several cases of lung injury in persons who reported use of electronic cigarette (e-cigarette), or vaping, products (1,2). To describe the characteristics of medical care, potentially related conditions, and exposures among 83 patients in Utah, detailed medical abstractions were completed for 79 (95%) patients. Among patients receiving chart abstractions, 70 (89%) were hospitalized, 39 (49%) required breathing assistance, and many reported preexisting respiratory and mental health conditions. Interviews were conducted by telephone or in person with 53 (64%) patients or their proxies, and product samples from eight (15%) of the interviewed patients or proxies were tested. Among 53 interviewed patients, all of whom reported using e-cigarette, or vaping, products within 3 months of acute lung injury, 49 (92%) reported using any products containing tetrohydrocannabinol (THC), the principal psychoactive component of cannabis; 35 (66%) reported using any nicotine-containing products, and 32 (60%) reported using both. As reported in Wisconsin and Illinois (1), most THC-containing products were acquired from informal sources such as friends or illicit in-person and online dealers. THC-containing products were most commonly used one to five times per day, whereas nicotine-containing products were most commonly used >25 times per day. Product sample testing at the Utah Public Health Laboratory (UPHL) showed evidence of vitamin E acetate in 17 of 20 (89%) THC-containing cartridges, which were provided by six of 53 interviewed patients. The cause or causes of this outbreak is currently unknown (2); however, the predominant use among patients of e-cigarette, or vaping, products with prefilled THC-containing cartridges suggests that the substances in these products or the way in which they are heated and aerosolized play an important role in the outbreak. At present, persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific cause or causes of lung injury are not yet known and while the investigation continues, persons should consider refraining from use of all e-cigarette, or vaping, products. During August–October 2019, possible cases of e-cigarette, or vaping, product use–associated lung injury (EVALI) in Utah were investigated to determine symptoms, medical care history, and exposures related to the injury. Cases were classified as confirmed or probable according to established case definitions (3). Medical record abstraction was completed using a detailed form provided by CDC in September 2019. Interviews were conducted with patients, or a proxy (a spouse or parent), using an adaptation of a questionnaire developed in Illinois and Wisconsin in consultation with CDC during investigation of cases in those states (1). Medical record abstractions were conducted by UDOH staff members. Interviews were conducted by UDOH staff members or local health department staff members in-person or by telephone to assess product acquisition and use behaviors. UDOH and Utah local health departments collected e-cigarette, or vaping, products from patients for testing using gas chromatography–mass spectrometry at UPHL to identify peaks for known chemical substances (including nicotine and THC) through nontargeted testing followed by partial verification of results with targeted tests for analytes that have known chemical standards (nicotine and vitamin E acetate, along with 16 others*) or known m/z values (i.e., mass) and relative retention times (myclobutanil and thiodiglycol) (4). During August 6–October 15, 2019, 83 confirmed and probable cases of EVALI were reported, primarily by clinicians and Utah Poison Control Center, to UDOH. The overall prevalence was 26 per 1,000,000 population. Most (86%) of the patients lived in Salt Lake County and surrounding urban counties (Davis, Morgan, Weber, and Utah); 14% lived in outlying counties. Abstraction of medical records was completed for 79 (95%) patients, and 53 (64%) interviews were completed. Among the 83 patients, 69 (83%) were male, and the median age was 26 years (range = 14–66 years) (Table 1). Among the 79 patients for whom medical record data were available, 70 (89%) were hospitalized during June 5–September 23 (median duration = 4 days; range = 1–17 days), including 35 (44%) who required intensive care unit (ICU) admission; nine (11%) were not hospitalized. Many patients required respiratory support; continuous or bilevel positive airway pressure was required by 30 (38%), and endotracheal intubation and mechanical ventilation was required by nine (11%). Fifty-nine (75%) patients were treated with steroids. Twenty (25%) patients received a diagnosis of acute respiratory distress syndrome. Patients reported having histories of asthma, 16 (20%); anxiety, 27 (34%); depression, 18 (23%); hypertension, four (5%); and heart failure, one (1%). Approximately half of the patients had at least one of these preexisiting conditions. Patients also reported smoking combustible marijuana (43%), tobacco (54%), or both (24%). Among the 53 patients interviewed, 49 (92%) reported use of THC-containing e-cigarette, or vaping, products during the 3 months preceding illness (Table 2); 35 (66%) reported using nicotine-containing products; and 32 (60%) reported using both THC- and nicotine-containing products. Seventeen (32%) patients reported exclusive use of THC-containing products, whereas three (6%) reported exclusive use of nicotine-containing products. Use of three brands of prefilled THC-containing cartridges was reported frequently by patients; these included Dank Vapes (21, 40%), Rove (19, 36%), and Golden Gorilla (11, 21%). Seventeen (32%) patients reported using more than one of these brands. Patients reported a total of 131 e-cigarette, or vaping, products used during the 3 months before illness and for which the method of acquisition was known; 84 of these were THC-containing products, and 47 were nicotine-containing products (Table 3). Most THC-containing products were acquired through informal sources, including friends (44%), in-person dealers (25%), and online dealers (24%). Five products were purchased at an out-of-state dispensary and one at an in-state vape shop selling these products illicitly. Among 84 THC-containing products used, frequency of use was reported for 70 of 84 (83%). Approximately two thirds (65%) of the THC-containing products were used ≤5 times per day. Among 47 nicotine-containing products used, frequency of use was reported for 29 of 47 (62%). The majority of the nicotine-containing products were used >25 times per day (55%) and were acquired primarily through in-state vape shops (49%) or convenience stores and gas stations (18%). To date, UDOH and Utah local health departments have collected 72 products from eight (15%) of 53 patients interviewed. Products tested at UPHL comprised 19 prefilled THC-containing cartridges from six patients and 20 nicotine-containing vaping liquids (19 bottled e-liquids and one from an atomizer) from six patients; six patients provided both THC- and nicotine-containing samples, and two provided only nicotine-containing samples). Among the 19 THC-containing cartridges, THC was detected in 19 of 19 (100%), nicotine was detected in one (5%), and evidence of vitamin E acetate was detected in 17 (89%). Samples of nicotine-containing e-liquid, in contrast, only showed evidence of nicotine and no evidence of THC or vitamin E acetate. No other analytes were found.

Summary What is already known about this topic? An outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI) of unknown source is ongoing in the United States. What is added by this report? Medical abstractions were completed for 79 Utah patients, 53 of whom were interviewed. Almost all patients reported using tetrahydrocannabinol (THC)-containing vaping cartridges. Most patients were hospitalized, half required breathing assistance, many reported preexisting respiratory and mental health conditions, and many identified as current or former smokers of combustible marijuana or tobacco. Most THC-containing products, acquired from six patients and, tested at Utah Public Health Laboratory, contained vitamin E acetate. What are the implications for public health practice? At present, persons should not use e-cigarette, or vaping, products containing THC. In addition, because the specific cause or causes of lung injury are not yet known and while the investigation continues, persons should consider refraining from use of all e-cigarette, or vaping, products.

Nathaniel Lewis, PhD1,2; Keegan McCaffrey2; Kylie Sage, MS2; Chia-Jung Cheng, PhD2; Jordan Green, MPH2; Leah Goldstein2; Hillary Campbell2; Deanna Ferrell, MPH2; Nathan Malan, MPH2; Nathan LaCross, PhD2; Alejandra Maldonado, PhD2; Amy Board, PhD1; Arianna Hanchey, MPH3; Dixie Harris, MD4; Sean Callahan, MD5; Scott Aberegg, MD5; Ilene Risk, MPH6; Sarah Willardson, MPH7; Amy Carter8; Allyn Nakashima, MD2; Janae Duncan, MPA2; Cindy Burnett, MPH2; Robyn Atkinson-Dunn, PhD2; Angela Dunn, MD2 (View author affiliations) Corresponding author: Nathaniel Lewis, [email protected], 801-538-9465. Top 1Epidemic Intelligence Service, CDC; 2Utah Department of Health; 3National Center for Environmental Health, CDC; 4Intermountain Healthcare, Salt Lake City, Utah; 5University of Utah Health, Salt Lake City, Utah; 6Salt Lake County Health Department, Salt Lake City, Utah; 7Davis County Health Department, Clearfield, Utah; 8Weber-Morgan Health Department, Ogden, Utah.

E-cigarette Use, or Vaping, Practices and Characteristics Among Persons with Associated Lung Injury — Utah, April–October 2019 Early Release / October 22, 2019 / 68 https://www.cdc.gov/mmwr/volumes/68/wr/mm6842e1.htm?s_cid=mm6842e1_w

Supplementary Table S1. Patient Demographics and Clinical Findings Age/Sex (Case #) Year Presenting Symptoms Duration of Symptoms At Time of Biopsy Medical History Occupational Exposures Smoking / Drug Use History Vaping History Serology/ Microbiology CDC Case Designation 44 M (#1) 2016 Acute presentation with 2-day history of hemoptysis and dyspnea 3 days None None Former tobacco smoker, 2.5 packyears Began vaping at the time of smoking cessation, 2 years before presentation Extensive serologic and infectious workup negative, ESR low Confirmed 42 M (#2) 2017 Acute hypoxic respiratory failure Approximately 1 week GERD, HTN Possible exposure to mold Former tobacco smoker, 20 packyears Started vaping to stop smoking approximately 1 year prior to presentation Unknown Probable 51 M (#3) 2019 Progressive subacute dyspnea and cough Approximately 4 weeks Obesity, asthma None Denied Vaping marijuana Infectious workup negative except for positive IgM for Mycoplasma pneumonia Probable 23 F (#4) 2019 Acute presentation with cough, myalgias, fever, nausea, vomiting, and respiratory failure eventually requiring intubation Acute, but further details unknown Anxiety, depression None Unknown Vaping THC for several months with tank style vaping device Infectious workup negative; positive ANA, elevated procalcitonin, and remaining serologic testing negative Confirmed 34 F (#5) 2019 Dyspnea and cough, progressing to acute respiratory failure requiring intubation 1 month Obesity None Unknown History of vaping, no details known Extensive serologic and infectious workup negative Confirmed 25 M (#6) 2019 Acute presentation with fever and cough, developed pneumomediastinum, highgrade fever, and respiratory failure requiring intubation. Acute, but further details unknown None Unknown Remote history of tobacco smoking History of vaping nicotine and mixing with cannabis oils Extensive serologic and infectious workup negative Confirmed 21 M (#7) 2019 Acute presentation with nausea, vomiting, fevers, night sweats, weight loss, progressive cough, pleuritic pain, and chest tightness 15 days IBD None Denied Vaping nicotine for 5 years; on weekend prior to presentation, started vaping nicotine with marijuana for the first time Extensive infectious workup negative; CRP 274, ESR 90, procalcitonin slightly elevated Confirmed 27 M (#8) 2019 Acute presentation with flu-like symptoms, fever of 40.6ºC, 2 days None None Former tobacco smoker Vaping cannabis daily Extensive serologic and Confirmed 22 nausea, vomiting, cough, and dyspnea progressing to respiratory failure requiring intubation infectious workup negative 38 M (#9) 2019 Acute respiratory failure, fevers, diarrhea, nausea, and vomiting Acute, but further details unknown Anemia, OSA None Denied Multiyear history of vaping with “heavy” use of CBD oil Extensive serologic and infectious workup negative Confirmed 34 F (#10) 2019 Acute presentation with dyspnea, fever, and suspected pneumonia treated with antibiotics without improvement; developed hypoxic respiratory failure requiring oxygen Acute, but further details unknown Anxiety None Denied “Heavy” vaping use over the past few months; vaping with cannabis Extensive serologic and infectious workup negative Confirmed 28 M (#11) 2019 Acute presentation with dyspnea Acute, but further details unknown Generalized anxiety disorder, opioid and ethanol use Unknown Denied tobacco smoking, but current marijuana smoker 1-year history of vaping 20-30 cartridges per day, also vaping THC Extensive serologic and infectious workup negative except for positive Aspergillus antibody in serum Probable 35 M (#12) 2019 Acute presentation with dyspnea and cough, with subsequent pneumothorax Acute, but further details unknown Previous admission months prior for respiratory failure, treated with steroids Unknown Former tobacco smoker, occasional marijuana smoking History of vaping for months previously and prior to present admission Unknown Probable 54 F (#13) 2019 Acute hypoxic respiratory failure with worsening dyspnea 2 weeks ADHD, anxiety, bipolar disorder, COPD, depression, diabetes, HTN, hepatitis C with cirrhosis Unknown Current tobacco smoker, 45 packyears History of vaping prior to presentation with nicotine and cannabis oil Negative respiratory viral panel, but other details unavailable Probable 67 M (#14) 2019 Subacute presentation with dyspnea and cough, rapidly progressing and requiring intubation. Acute, approximately 9 days None Unknown Current tobacco smoker History of vaping prior to presentation Extensive serologic and infectious workup negative Confirmed 19 M (#15) 2019 Acute presentation with abdominal pain, nausea, vomiting, and fever 4 days None Unknown Current marijuana smoker Vaping several times per week for several months, including cannabis oils Extensive serologic and infectious workup negative Confirmed 39 M (#16) 2019 Cough, dyspnea, night sweats, intermittent fevers, and fatigue 2 months Asthma None Remote tobacco smoker for 2 years; “Significant” vaping of non-nicotine ANA titer 1:40, remaining Confirmed 23 for 6 weeks current marijuana smoker products at time of presentation, further details unavailable serologic and infectious workup negative 40 M (#17) 2019 Worsening cough, myalgias, dyspnea, and fever for 1 week 1 week None Unknown Unknown Vaping for last 6 years, and vaping synthetic cannabinoids from “black market” for last 6½ months Cultures negative, serologic testing unavailable Probable ADHD, attention deficit hyperactivity disorder; ANA, Anti-Neutrophil Antibody; ANCA, Anti-Neutrophilic Cytoplasmic Antibody; CBD, cannabidiol; CDC, Centers for Disease Control and Prevention; COPD, chronic obstructive pulmonary disease; CRP, C-Reactive Protein; ESR, Erythrocyte Sedimentation Rate; GERD, Gastroesophageal Reflux Disease; HTN, Hypertension; IBD, Inflammatory Bowel Disease; OSA, obstructive sleep apnea; THC, tetrahydrocannabinol https://www.nejm.org/doi/suppl/10.1056/NEJMc1913069/suppl_file/nejmc1913069_appendix.pdf

Most Utah cases are in their 20s or 30s. The median age in Utah is 26, which is three years older than the current national median age of 23. Men account for 82% of the Utah cases while women account for 18%, which is similar to case demographics seen in other states. The majority of cases in Utah have symptom onset dates beginning in late July. Ninety-two percent of cases self-reported vaping THC cartridges and 66% self-reported vaping nicotine. Sixty percent of cases also self-report vaping both substances (60%). Substance # of Cases Percentage Any THC cartridges 49 of 53 92% Any nicotine 35 of 53 66% Both THC & nicotine 32 of 53 60% THC only 17 of 53 32% Nicotine only 3 of 53 6% *Data in the above table are current as of Oct. 15, 2019 Most THC products were acquired through friends, online, and in-person dealers. A small percentage of THC products were acquired at out-of-state dispensaries or purchased at vape shops in Utah. Nicotine products were acquired mostly at vape shops in Utah. *Data in the above chart are current as of Oct. 15, 2019 The UDOH Utah Public Health Laboratory (UPHL) has been working with state and national laboratories to test products used by case patients. Thirty-nine samples were tested at the UPHL for several chemical compounds including illicit drugs (e.g., opioids, fentanyl, and methamphetamines), cutting agents, and biologic toxins. Of the 39 products tested by the UPHL, 19 were THC cartridges and 20 were nicotine e- juices. Almost all THC cartridges tested contained vitamin E acetate, a known cutting agent. In contrast, no nicotine products tested showed any unexpected compounds. Samples Tested Containing THC Containing Nicotine Containing Vitamin E THC Samples 19 100% 5% 89% Nicotine Samples 20 0% 100% 0% *Data in the above table are current as of Oct. 15, 2019

As of Monday, October 21, 2019, 98 cases of vaping-related lung disease have been reported in Utah, with an additional 15 potential cases being investigated. The state has also reported one death associated with the outbreak. Given the evidence, vaping THC cartridges or “carts” is likely the driver of this outbreak of severe lung injury. The UDOH recommends people do not vape THC cartridges until we learn more. https://health.utah.gov/lung-disease-investigation/lung-injury-outbreak-data

Since June 2019, CDPH has received reports that 135 people in California who have a history of vaping were hospitalized for severe breathing problems and lung damage, and three people have died. https://www.cdph.ca.gov/Programs/CCDPHP/Pages/Vaping-Health-Advisory.aspx

Pathology Insights: Pathology of Vaping-Associated Lung Injury Sanjay Mukhopadhyay, MD (@smlungpathguy), Director of Pulmonary Pathology at Cleveland Clinic, discusses the findings of a study on the lung pathology of vaping. Featured in an article co-authored by Dr. Mukhopadhyay and published in the American Journal of Clinical Pathology, the study focuses on the results of microscopic examination of biopsied lung tissue from individuals who developed severe lung illness associated with vaping. This is one of the first case series in the world to examine lung biopsies from patients with vaping-associated lung illness and is the first-ever study on vaping published in a pathology journal. These findings have important public health implications and are detailed in the video below: https://clevelandcliniclabs.com/2019/10/21/pathology-insights-pathology-of-vaping-associated-lung-injury/

Current Cases: 12* (Age range: 16–44 years)*As of October 17, 2019 (Case count updated every Thursday) https://doh.sd.gov/News/ecigarettes.aspx

SAN FRANCISCO — For years, a divisive debate has raged in the United States over the health consequences of nicotine e-cigarettes. During the same time, vaping of a more contentious substance has been swiftly growing, with scant notice from public health officials. Millions of people now inhale marijuana not from joints or pipes filled with burning leaves but through sleek devices and cartridges filled with flavored cannabis oils. People in the legalized marijuana industry say vaping products now account for 30 percent or more of their business. Teenagers, millennials and baby boomers alike have been drawn to the technology — no ash, a faint smell, easy to hide — and the potentially dangerous consequences are only now becoming evident. Most of the patients in the outbreak of severe lung illnesses linked to vaping — which has left 1,479 people sick and 33 dead so far — vaped THC, the ingredient in marijuana that makes people high. Until more information is known, officials at the Centers for Disease Control and Prevention have warned people not to vape cannabis products. To some scientists, and even industry leaders, warning signs have been apparent for years as vaping cannabis grew in the shadows, propelled by a patchwork of regulations, a wave of state-by-state legalization and a soaring supply of low-cost marijuana. While the government and researchers poured resources into studying e-cigarettes, federal rules sharply limiting research into the health effects of cannabis — because it is classified as a controlled substance with a high potential for abuse — have left a void in scientific knowledge about what THC vaping does to the lungs. Last year, Dr. Neal Benowitz, a professor of medicine and a researcher on nicotine and vaping at the University of California, San Francisco, sent a letter to Congress warning of the risks posed by leaving a hugely popular practice unstudied. “Very little is known about the safety or effects of vaped cannabis oil,” he wrote, cautioning that some ingredients mixed into the oils “could have harmful, toxic effect on users, including the potential for causing and/or promoting cancer and lung disease.” “It’s disgraceful,” Dr. Benowitz said in a recent interview as reports of hospitalizations and deaths from vaping-related lung illnesses mounted. “I’m not able to take products we think are potentially harmful and do analysis. I can buy a vape device around the corner, but I can’t bring it into the lab and test it.” Even members of the legalized marijuana industry acknowledge the lack of hard science about the cannabis vaping products they sell. “There’s a glaring gap in trying to understand this product,” said Jerred Kiloh, president of the board of the United Cannabis Business Association, which represents 165 marijuana dispensaries in California, where marijuana was legalized for recreational use in 2016. Mr. Kiloh, who owns the Los Angeles dispensary Higher Path, said he believed that the vape pens sold in his stores and in other licensed and regulated stores are likely safe because the ingredients were measured and tested by the state. The Bureau of Cannabis Control did not return calls asking for comment. Vaping oils typically include other additives, solvents and flavor enhancers, and health investigators believe some such ingredients, including vitamin E acetate, could be responsible for some of the lung illness cases. The problem of unknown and potentially dangerous additives, Mr. Kiloh and others said, is vastly worse in a soaring black market in the nearly 40 states where recreational marijuana is still illegal. Even in states where the drug is legal, counterfeit cartridges are cheaper than the licensed, tested and taxed products. It is hard for legal players who pay taxes to compete. A regulated vape pen with half a gram of THC costs $55, compared with $25 or less on the street for an untested product. “We don’t know what the chemical composition is,” Mr. Kiloh said, “and we especially don’t know what the chemical composition is once it’s been combined, heated and inhaled.” No Ash, No Rolling Papers In the earliest days of cannabis vaping, a small group of innovators saw the technology as a safer way to help medicinal marijuana patients. They hoped that vaping — which entails heating THC so that it turns to an aerosol — would be less harmful to the lungs than inhaling combusted marijuana. But that ethos quickly gave way to a different lure: the pure convenience of vaping, which allowed users to avoid rolling joints, spilling ash, giving off a telltale smell — or getting caught. Vape pens brought the sheen of high technology to a drug associated with hippies and grunge, along with the discretion of, say, texting beneath the dinner table. “You could vape in a police station and no one would even know, not that you’d want to do that,” said a 35-year-old man outside Harvest, a marijuana dispensary in San Francisco, who declined to give his name because he said he did not want to hurt his job-hunting prospects. Other Harvest customers said they once embraced vaping but now have doubts. “It’s convenient, neat, easy. No lighter,” said Michael, who, with his wife, Laurie, both in their 70s, declined to give a last name because they didn’t want their teenage granddaughter to know about their habit. With news of vaping-related hospitalizations and deaths, though, Laurie was growing concerned. So this time she came to Harvest to buy flower, the old-fashioned bud rolled in joints. It was a switch the couple said they would continue while they await more vaping science. Others were undeterred. Cynthia Valdivia, 34, bought a THC vape cartridge after using one to try marijuana for the first time this summer. She said she was not worried about what she bought from a legal store. “There’s someone behind the brand and they don’t want to kill people,” she said. “They want their money.” The Volcano The market has flourished in the absence of regulation, said Eric N. Lindblom, a former tobacco official at the Food and Drug Administration. The federal government, he said, has been unsure of how to respond to state legalization of marijuana, and the uncertainty has left a void of regulation, research and enforcement. “Only now that we have this special, extra weird mystery crisis with the disease and deaths is there now interest in doing something,” he said. Some think it may be too late. “The market has run amok,” said Carlos de la Torre, the owner of Cornerstone Wellness, a dispensary in Los Angeles. Mr. de la Torre came to the cannabis business in 2007 after a career in television advertising. That year he opened his shop in a Los Angeles suburb, selling marijuana flower and edibles to customers with medical cards. “At the time, I don’t think vaping really existed,” he said. Not commercially, at least. There was a rich and informal history among a narrow band of regular marijuana users who bathed weed in alcohol to extract THC — so-called honey oil or hash oil. That was the domain of the “biker, LSD, hippie crowd,” said David Downs, the California bureau chief of Leafly, a cannabis news and product website. The first commercial marijuana vaping brand was called the Volcano, and it was the brainchild of a German entrepreneur, Markus Storz, who obtained a patent for it from his native country in 1999. Image The Volcano came to the United States in 2003, and it is aptly named. It is built on a sturdy, triangular-shaped base — “the kind of thing that sat on a coffee table and weighed a pound,” Mr. de la Torre said. It heated marijuana flower until the THC baked off as vapor. A user then inhaled the aerosol from a large plastic bag attached to an inhalation pipe. Industry insiders thought it might be healthier than smoking a joint because burning marijuana contains carcinogens like tar and carbon monoxide. “If we were really helping cancer patients, then adding carcinogens was not helpful,” said Mr. Kiloh, who in 2003 opened his first medical dispensary, Green Cross, in San Francisco, seven years after California legalized marijuana for medical purposes. Federal research restrictions allow the study of marijuana under certain conditions, and scientists at the University of California, San Francisco, found that the Volcano produced less carbon monoxide and tar compared with smoking marijuana. The Volcano was built around inhalation of pure marijuana vapor, created by heating the plant itself. In a few years, the technology would change in a fundamental way. “What happened was that the oil came next,” Mr. Kiloh said. Entrepreneurs began to extract oil by bathing the leaf in ethanol or butane, filtering out the solid material that remained and then evaporating the solvent to leave the concentrated oil. Another method used carbon dioxide, which, when pressurized, creates a fluid that can used to extract the oil. (There is no “toxicological” research about the relative health effects of the different methods, according to Christopher Havel, an analytical chemist at U.C.S.F. who works with Dr. Benowitz). Once extracted, the THC oil could then be heated up using a small battery, kept in a cartridge or penlike case, creating aerosol, which is then inhaled from one end of the device. Consumers fell in love. As marijuana became legal in a growing number of states, a new area of entrepreneurship burgeoned. Businesspeople found they could use the entire plant to extract oil rather than throw away stems and other parts discarded by smokers, which maximized the value of the crop. The oil also could be mixed with other additives to give flavor, to create the effect of big puffs of smoke or just to cut the THC to substitute less expensive chemicals. At the time, Mr. Kiloh was dubious: What was in these things? The packages either did not list ingredients or, if they did, the labels seemed untrustworthy, he said, because the oil sometimes smelled off. Sometimes he would test the product and discover the THC had been watered down, initially with propylene glycol, which is used in fog machines, to add a smokey luster. “People started getting greedy,” Mr. Kiloh said, describing the early vape pen manufacturers around 2012. “You didn’t know how much was propylene glycol and how much was THC.” After initially carrying the vape pens in his dispensary, Mr. Kiloh temporarily pulled them from his shelves. “I didn’t want to sell them,” Mr. Kiloh said. “What people said for the next three or four months was, ‘Can you bring them back?’” But he told them he wasn’t sure the pens were safe. Mr. Downs, of Leafly, said the worry was valid. “It’s very clear innovation has eclipsed the sophistication of consumers as well as regulators and investigators,” he said. “We’ve been engaging in an uncontrolled mass experiment with inhaling concentrations of cannabinoids.” In states that legalized marijuana, farmers could grow the crop openly, creating a vast, lower-cost supply that flooded not just legal markets but spilled into illegal ones, said Beau Kilmer, director of the Rand Drug Policy Research Center. Prices plummeted. While national figures are hard to come by, Rand’s research shows that an oversupply in Oregon caused the price per pound to fall more than 50 percent, from $1,250 in 2016 to $500 in 2018. Much of the product went to oil. “The fastest growing segment of the market is extract for inhalation,” Mr. Kilmer said. And researchers remain in the dark. In August, the Drug Enforcement Administration loosened rules to allow some scientific institutions to apply to grow their own marijuana for study. However, the restrictions still prevent researchers like Dr. Benowitz from examining the kind of THC oil sold widely on the legal and black markets. He summed up what little is known about vaping THC oil: “All we know is that there weren’t many problems until recently.” Matt Richtel is a best-selling author and Pulitzer Prize-winning reporter based in San Francisco. He joined The Times staff in 2000, and his work has focused on science, technology, business and narrative-driven storytelling around these issues. @mrichtel ADVERTISEMENT

NY Times report detailing the history of Marijuana / THC vaping. Marijuana and Vaping: Shadowy Past, Dangerous Present A technology initially promoted to help cigarette smokers has transformed marijuana use, too. Now, with cases of severe lung illness rising, health investigators are warning people to stop vaping cannabis. By Matt Richtel Oct. 21, 2019, 3:00 a.m. ET https://www.nytimes.com/2019/10/21/health/marijuana-and-vaping-shadowy-past-dangerous-present.html?smid=tw-nytimesscience&smtyp=cur