niman

Anne Schuchat expects this week's numbers to "grow considerably"

Panel 2 Meredith Berkman Co-Founder and Parent, Parents Against Vaping e-cigarettes (PAVe) Berkman Testimony Renee D. Coleman-Mitchell MPH Commissioner, Connecticut Department of Public Health Coleman-Mitchell Testimony Coleman-Mitchell Bio Bonnie Halpern-Felsher Ph.D. Professor of Pediatrics, Executive Director of the Stanford Tobacco Prevention Toolkit, Stanford University Halpern-Felsher Testimony Halpern-Felsher Bio Sally Satel M.D. Resident Scholar, American Enterprise Institute Satel Testimony Satel Bio

Panel 1 Anne Schuchat M.D. Principal Deputy Director, Centers for Disease Control and Prevention Schuchat Testimony Schuchat Bio

E-cigarettes: An Emerging Threat to Public Health Date: Wednesday, October 16, 2019 - 10:00am Location: 2358-C Rayburn House Office Building, Washington, DC 20515 E-cigarettes: An Emerging Threat to Public Health Subcommittees: The Departments of Labor, Health and Human Services, Education, and Related Agencies (116th Congress)

House Appropriations hearing 10 AM 10/16/19 https://appropriations.house.gov/events/hearings/e-cigarettes-an-emerging-threat-to-public-health

Organization / Date Updated Confirmed and Probable Cases Cases Under Investigation Deaths ACHD / October 10, 2019 12 6 0 https://www.alleghenycounty.us/Health-Department/Resources/Data-and-Reporting/Chronic-Disease-Epidemiology/Lung-Disease-Associated-with-Vaping.aspx

As of October 11, Kansas has had two confirmed deaths related to vaping. Kansas currently has 15 probable/confirmed vaping related cases, including the two deaths. Of the cases, 73% are male and the collective ages range from 15-67 years old. 13 of the 15 were hospitalized and one remains hospitalized. http://www.kdheks.gov/vaping/index.htm

Vape Pen Vivisection (preview) 10/14/2019 12 Comments Y'all have been very patient with my painstaking approach (particularly my partner, Cindy); I am being appropriately careful about some of the conclusions drawn. Here's a preview of Vape Pen Vivisection: Power Supply Connectors A picture is worth a thousand words. These will be posted in higher resolution in the final version. The top photo compares an auto vape pen to a non-auto vape pen (("external on/off switch"). The second photo is the external view of a #510 female thread connector (battery case removed) that connects to the male thread vape cartridge. The third photo shows what is not typical visible: the internal view of six (6) vape pen power modules, and specifically the solder points connecting the battery and control circuit to the underside of the #510 femaled-thread connector (which connects to #510 male-thread cartridges to power heating coil). The Liquid A visible air channel in the center flange is how e-liquid enters the battery compartment. The underside of one of the #510s even has obvious verdigris (green scale from oxidized copper), probably from exposure of internal coper wiring to liquid condensing in the compartment. The Metal The most significant take-home message is that there is a risk of short circuit between the large proximal globules of solder connecting the circuitry to the #510. In some cases (the far left example), the risk is minimal, but not in those with red circles. The solder points there are quite large and separated by no more than a millimeter or two. These solder points can be bridged by liquid entering the compartment and short circuit. Short circuits generate considerable heat and lead to solder fume production directly in the inhalation path of the vape pen user. As an aside, I got to experience the phenomenon first hand when disassembling one of the pens. A short circuit caused a nasty little fire and plume of greyish-white smoke. I made a very undignified shriek and smothered the fire in a bucket of sand. I was working in the fume hood (no danger of exposure), but it was quite startling. Cautionary note: Curiosity killed the cat, and more than a few scientists. Please don't play this way without safety precautions and appropriate PPE.

Vape Pen Vivisection (preview) 10/14/2019 12 Comments

Part II of Colorado Green Lab blog on role of solder in EVALI (#vaping lung injury) http://www.coloradogreenlab.com/blog/vape-pen-vivisection-preview

Cadmium Pneumonitis A far more serious form of metal fume fever occurs after inhalation of cadmium oxide fumes. The immediate effects are similar to those described above ("flu-like"), but unlike zinc oxide exposure, cadmium fume inhalation causes significant lung damage post-exposure (pneumonitis), and can progress to hypoxia, respiratory failure, and death. The table below compares the clinical presentation of zinc oxide metal fume fever (MFF), cadmium pneumonitis (CP), and vaping-associated pulmonary injury (VAPI). High Index of Suspicion Silver solder (often contains cadmium) is used to make stable unions between dissimilar metals such as copper and stainless steel. In lower-end vape pens, large beads of this type of solder are present on positive and negative heating element connections. Most vape pens use cadmiun-free solder. Unscrupulous manufacturers have a financial incentive to cut corners. It's happened before: https://en.wikipedia.org/wiki/2008_Chinese_milk_scandal Motive Money and ease of use. Cadmium-containing silver solder is less expensive than cadmium-free alternatives, and has improved flow properties which facilitate the joining of dissimilar metals found in vape pen electrical components. Means Cadmium is highly toxic to multiple organ systems. Upon inhalation, cadmium elicits a dose-dependent burst of inflammatory cytokines that promote the systemic effects (fever, headache, joint pain, etc) observed in metal fume fever (Blum, Rosenblum et al. 2014). Cadmium fumes also directly injure lung cells, leading to fluid accumulation, impaired lung function, and respiratory failure. Following absorption into the bloodstream, protein-bound cadmium slowly accumulates in the kidneys and may result in renal injury. Opportunity Upwards of 20-30 mg of solder alloy is permeated with vape juice liquid and directly in the airflow path through the vape pen. Assessment Blood cadmium levels are indicative of recent exposure, whereas urinary cadmium is indicative of chronic, longer term exposure. Normal blood cadmium is <5.0 ng/mL, with most results in the range of 0.5 to 2.0 ng/mL, whereas tobacco smokers typically have blood and urinary cadmium levels more than double those of nonsmokers (Mannino, Holguin et al. 2004). ©2019 COLORADO GREEN LAB | COLORADOGREENLAB.COM Continued in Part 2: Vape Pen Vivisection

tl;dr;dr 19_1006 update: Signs and symptoms of vaping-associated pulmonary injury (VAPI) are consistent with chemical inhalation. Analysis of symptoms, commonality of exposure source (vape pen battery cartridges), and mechanism ("vaping") may indicate cadmium-derived metal oxide fume inhalation (metal fume fever, cadmium pneumonitis) as a possible cause of the syndrome ("VAPI"). tl;dr Public service announcement: Clinicians, when you hear vaping, think zebras, not horses. The early symptoms of VAPI are often mild and resemble pneumonia ("horse"). Many of the VAPI ("zebra") patients presented in an outpatient setting, were initially diagnosed with respiratory infections, and treated with antibiotics (without improvement). Workups were negative for infectious agents, and chemical exposure of unknown type/origin is now believed to be the cause of VAPI. The majority of patients who develop this illness exhibit clinical improvement only after treatment with systemic corticosteroids. The CDC encourages clinicians to report possible cases of e-cigarette or vaping-associated lung injury to their local or state health department for further investigation: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease/healthcare-providers/index.html tl Vapi Data Set. The VAPI data set published (September) in the New England Journal of Medicine (Layden, Ghinai et al. 2019) is the most comprehensive study to date, and includes clinical findings from 53 patients in Illinois and Wisconsin (Full text: https://www.nejm.org/doi/full/10.1056/NEJMoa1911614). Unless otherwise indicated, signs, symptoms, data, etc are in reference to this publication. July/August 2019. Hundreds of patients with an unusual respiratory illness began popping up in clusters across the United States. In the days and weeks prior to their hospitalization, these patients exhibited typical signs and symptoms of pneumonia and most were prescribed antibiotics as the first course of treatment. None of the patients (who were eventually diagnosed with vaping-associated pulmonary injury; VAPI) improved on antibiotics and lab workups revealed no evidence of pulmonary infection. The full range of findings is conflicting and no clear pattern has emerged regarding the source or cause of the illness. Symptomatology Patients have highly similar clinical characteristics and all developed the illness within a similar timeframe. All reported use of THC or nicotine e-cigarette devices ("vaping") prior to illness All displayed signs of damaged lung tissue Most progressed to hypoxemia and required hospitalization Some progressed to respiratory failure The majority of patients exhibited clinical improvement after treatment with systemic corticosteroids Most reported constitutional/gastrointestinal symptoms that preceded the onset of respiratory symptoms Vaping Products Most patients reported using vaping devices with THC and nicotine cartridges, but some reported exclusive use of only THC or only nicotine. A wide variety of cartridge brands and products were reported. US-wide, US-specific Cases are not specific to any one region of the United States, but the syndrome appears to occur only in vape users in the United States. Other parts of the world with a high prevalence of vaping (ex. the European Union) are not reporting similar illnesses. More on that in second and third part of series. Correlation ≠ Causation The underlying cause is now believed to be chemical exposure, and not an infectious disease. The VAPI syndrome is strongly correlated with the use of black market THC vape cartridges, but the CDC has yet to conclusively identify a vaping product, substance, or additive common to all cases. Metal Fume Fever Unless you're a metalworker, work for OSHA, or, in my case, previously employed at a respiratory hospital, you've probably never heard of Metal Fume Fever (MFF). There are only 1500-2500 cases of MFF reported in the United States each year, and the illness is typically restricted to individuals with very specific occupations (e.g. welders). MFF is caused by inhalation of metal-containing fumes (ex. zinc oxide) produced by welding, soldering, and brazing. Typical symptoms of metal fume fever are non-specific ("flu-like"), and can include cough, raised temperature ("fever"), headache, chills, aches, dizziness, and a sweet or metallic taste in the mouth. More severe exposure can result in gastrointestinal symptoms, including nausea, vomiting, and diarrhea. Metal fume fever caused by zinc oxide inhalation is the most frequently reported type of exposure and bears superficial resemblance to VAPI. Acute symptoms develop 4-12 hours following zinc fume exposure, but do not usually progress to lung damage. The zinc oxide-associated form of the illness typically self-resolves within 12- to 48-hours.

Part 1: Metal Fume Zebra 10/5/2019 29 Comments In the first of this three-part series on Vaping-Associated Pulmonary Injury (VAPI), I will introduce a compound with the motive, means, and opportunity to cause the illness. Part 2 will identify the common point of origin linking vape users in the United States and why Europe is unaffected, and, finally, Part 3 will outline a rational harm-reduction based approach for evaluating the safety and continued use of these products.

In the first of this three-part series on Vaping-Associated Pulmonary Injury (VAPI), I will introduce a compound with the motive, means, and opportunity to cause the illness. http://www.coloradogreenlab.com/blog/part-1-metal-fume-zebra

What is in the aerosols? Determining what’s in vaping products is a key part of understanding what’s causing the lung injuries. However, knowing what’s in vaping cartridges is not the same as knowing what’s going into people’s lungs. “You can test the oil all you want, but at the end of the day, what are you inhaling?” Medicine Creek Analytics’ Wise asks. “That is the most important part to test in my opinion.” Scientists at the CDC are analyzing the aerosols produced by some of the products consumed by patients with vaping illnesses, the CDC’s Schuchat testified at the September hearing. The analysis is complex because “users can modify the products, and the heating process can also influence the types and amounts of chemicals a user is exposed to,” she said. Cannabis testing labs are also investigating aerosols generated by various vaping products. Before the outbreak of lung illnesses hit the news, Medicine Creek Analytics ordered a vapor collection machine to test a filter device for a client to determine whether it removes pesticides, cannabinoids, and terpenes from cannabis vaping products, Wise says. The machine will be useful for understanding what is in the aerosol that people are vaping, she says. And then there’s the question of which of the chemicals in aerosols might harm lung tissues. Little is known about the toxicity even of branded e-cigarettes, let alone THC products. Scientists at the Institute for In Vitro Sciences (IIVS) are working with tobacco companies to evaluate the inhalation toxicology of products in development or on the market. They are using nonanimal, human cell–based testing platforms. The team is optimizing such tests for evaluating potential hazards associated with inhalable materials, including those from vaping devices, says Holger Behrsing, a principal scientist at IIVS. “As part of our expansion of respiratory toxicology testing, we do utilize long-term pulmonary models and conduct repeat exposure studies to better recapitulate potential human exposures,” Behrsing says. “We believe such an approach using human, multicellular, three-dimensional respiratory test systems will better allow us to detect key events that may lead to more severe, adverse pulmonary conditions.” As for the cause of the current lung injury crisis, the problem could be related to the battery, the heating element, or the cartridge itself, Wise says, pointing out that many devices are cheap and not very reproducible. In an Oct. 5 blog post, owners of Colorado Green Lab, a company that sells nonpsychoactive cannabidiol (CBD) and CBD delivery systems, suggest that cadmium solder used in cheap vape pens may be the cause of some vaping lung injuries. “Cadmium-containing silver solder is less expensive than cadmium-free alternatives, and has improved flow properties which facilitate the joining of dissimilar metals found in vape pen electrical components,” the company says. However, it adds, a “serious form of metal fume fever occurs after inhalation of cadmium oxide fumes.” Metal fume fever “is a condition in which the sufferer has influenza type symptoms—a raised temperature, chills, aches and pains, nausea, and dizziness,” says the Welding Institute, a research and technology organization specializing in welding. The institute adds that exposure to some metal fumes, such as cadmium, “can cause more serious illness or even death.” The cause of the outbreak is likely to be a combination of many factors, Wise says. “This situation really points to the need for oversight, regulation, and product safety testing.” The broader cannabis industry echoes that position. “If it is confirmed that Americans are being hurt because of unregulated, illicit market cannabis vape products, it is yet another reason for real, comprehensive federal cannabis reform that will allow the regulated, tested cannabis industry to displace illicit market actors,” says an Oct. 3 letter from the National Cannabis Industry Association to congressional leaders.

Searching liquids for a culprit While clinicians work on identifying and treating the lung injuries, others are actively looking for the cause. The FDA is analyzing samples of vaping products consumed by those who have developed lung injuries. The agency has received about 440 samples from 18 states, Sharpless says in the Oct. 4 statement. “More than half of the vaping liquid products have undergone some form of evaluation, with additional testing on these and other samples continuing daily,” he says. Scientists at the FDA’s Forensic Chemistry Center are analyzing the samples “using state-of-the-art methods to assess the presence of a broad range of chemicals, including nicotine, THC and other cannabinoids, opioids, cutting agents and other additives, pesticides, and toxins,” Sharpless testified at the Sept. 25 hearing. But such testing is limited, he noted, because many of the samples contain little to no liquid. Of the samples analyzed by the FDA, about 70% contain THC, Sharpless said at the hearing. About half of the samples that contain THC also contain vitamin E acetate, he noted. On Sept. 5, the New York State Department of Health pointed to vitamin E acetate, an oil used as a nutritional supplement and as a diluent or thickening agent in THC vaping cartridges, as a possible cause of the lung problems. It is unclear whether vitamin E acetate is the cause of the lung injuries or a marker of an adulterated product, Sharpless said at the hearing. Nonetheless, cannabis-testing labs are now starting to offer tests for vitamin E and vitamin E acetate in THC vaping cartridges. “It is not a standard test” in the cannabis industry, says Amber Wise, science director at Medicine Creek Analytics, a Seattle-based cannabis-testing lab. But vitamin E is used in many other products, such as lotions and nutraceuticals, “so analytical labs already have protocols,” she says. Thickening agents are common in illicit THC cartridges but are rarely added to legal products where testing for potency is required, says Jeffrey Raber, cofounder and CEO of the Werc Shop, a California-based cannabis contract manufacturing and testing firm. “THC concentrates are known to be thick and viscous when they are high potency,” Raber says. So when street dealers dilute illicit products with various agents to maximize profits, those products are typically less viscous. Consumers can visually detect the viscosity of the product by turning the cartridge upside down. If a bubble goes from the top to the bottom quickly, it usually means that the product has been cut with something, Raber says. Dealers mask that visual test by adding a thickening agent, so the bubble doesn’t move from the top to bottom as fast, and consumers think they are getting a high-potency product. The illicit cannabis market “is out of control and concerning,” even in states like California where recreational cannabis is legal, Raber says. In California, the cannabis black market is estimated to be three to four times the size of the legal cannabis industry, he notes. One source of the black market problem is that California requires testing of final finished cannabis products, Wise says. If a product fails the test, more often than not it doesn’t get thrown away. Instead, it enters California’s black market and is distributed to states where cannabis is illegal, she says. More recent reports suggest that pesticides in illicit THC products may be playing a role in the outbreak of vaping lung injuries. Last month, NBC News purchased THC vaping cartridges from both legal dispensaries and illicit dealers in California and sent the products to cannabis testing lab CannaSafe for analysis. The lab found no pesticides or other contaminants in the legally purchased products, but it found the fungicide myclobutanil in 10 of 10 illicit products tested for pesticides. When heated, myclobutanil produces hydrogen cyanide. Inhalation of hydrogen cyanide is fatal at high doses.

This is an updated version of a story originally published on Oct. 4, 2019. Credit: Shutterstock More than 1,200 people, mostly under 35, have developed serious lung injuries associated with vaping, but the cause is still unknown. No one knows for sure why more than 1,200 previously healthy people in the US, more than half of them under the age of 25, have developed serious lung injuries that require hospitalization and, in many cases, mechanical ventilation and intensive care. Twenty-six people had died from the mystery illness as of Oct. 8, according to the US Centers for Disease Control and Prevention. Health officials have ruled out an infectious agent. The only common link is that all the victims have admitted to vaping nicotine or tetrahydrocannabinol (THC)—the psychoactive component in cannabis that produces a high—or both. Federal, state, and local governments are scrambling to find answers to this emerging public health crisis. But after several months of investigation, “no one compound or ingredient has emerged as a singular culprit,” Norman “Ned” Sharpless, acting commissioner of the US Food and Drug Administration, says in an Oct. 4 statement. “We do know that THC is present in most of the samples being tested,” he says. As the number of serious lung injuries attributed to vaping grows, so do the number of possible explanations. Over the past few weeks, fingers have pointed at vitamin E acetate and pesticides in vaping liquids, as well as cadmium-containing solder used in vape pens. The ongoing investigation is particularly challenging because it involves nearly all US states, CDC principal deputy director Anne Schuchat told members of Congress at a hearing on Sept. 25. She added that “the investigation is complicated by the diversity of the e-cigarette or vaping product marketplace, with a multitude of products, a wide array of ingredients, and the intersection with potentially illicit substances such as marijuana.” The bottom line is that “users do not know what is in their e-cigarette or vape solutions,” Schuchat said. Even if they did know, little information is available on inhalation toxicity. Although the lung injuries may seem similar, “it is not clear if they have a common cause or if they involve different diseases with similar presentations,” Sharpless testified at the Sept. 25 hearing, held by the Subcommittee on Oversight and Investigations of the House Committee on Energy and Commerce. The latest evidence points to more than one type of illness. A group from WakeMed Hospital in North Carolina reported in early September that lung injuries in five people resembled lipoid pneumonia, a condition in which fats or oils deposit in the lungs (Morb. Mortal. Wkly. Rep. 2019, DOI: 10.15585/mmwr.mm6836e1). However, in a letter to the editor of the New England Journal of Medicine published on Oct. 2, Mayo Clinic and UnityPoint Health staff in Arizona, Florida, Illinois, and Minnesota report finding no evidence of lipoid pneumonia in lung tissue samples from 17 people with suspected vaping illness. The physicians instead point to lung inflammation “from one or more inhaled toxic substances” (DOI: 10.1056/NEJMc1913069).

Cause of mystery vaping lung illnesses remains elusive Little is known about the contents and toxicology of e-cigarette or THC products or their delivery devices by Britt E. Erickson OCTOBER 10, 2019 | APPEARED IN VOLUME 97, ISSUE 40

Chemical and Engineering News Nov 10 review of efforts to determine cause(s) of EVALI https://cen.acs.org/biological-chemistry/toxicology/Cause-mystery-vaping-lung-illnesses/97/i40

Total reported patients statewide: 125 (Updated: 10/15/2019) Breakdown of reported patients by region: Western New York: 31 Central New York: 13 Capital Region: 20 Northern New York: 2 Metropolitan Region (outside of NYC): 31 New York City: 25 Out of State: 3* *Patients treated at hospitals in NYS but are residents of another state. https://www.health.ny.gov/prevention/tobacco_control/campaign/e-cigarettes/

Year Reported Cases Year-to-Date Deaths Year-to-Date 2019 68 1 Report last updated on October 15, 2019 with data from January 01, 2019 - October 12, 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. http://www.flhealthcharts.com/ChartsReports/rdPage.aspx?rdReport=ChartsProfiles.LungInjuryE-CigaretteUse

Last night 11 ET Dr. Henry Niman PhDNew CDC Vaping News And Information