niman

Thread for British Columbia vaping (EVALI) cases.

Posted: Oct 17, 2019 / 08:18 PM CDT / Updated: Oct 17, 2019 / 09:04 PM CDT NASHVILLE, Tenn. (WKRN) – Tennessee’s first vaping death has been identified as a Minnesota man. The young man’s girlfriend told our ABC affiliate, KSTP, that her boyfriend bought the THC cartridges from friends, who told him they were purchased from a dispensary in Colorado. Cory Smallwood said her boyfriend, Evhen Cameron, used to smoke marijuana with a pipe but switched to vaping. The move to vaping cost Evhen his life. RELATED: First vaping-related death reported in Nashville 26-year-old Evhen Cameron had just recently moved to Nashville, where he passed away last Sunday. “It was very quick, very sudden, and very strange,” Smallwood told KSTP. Smallwood says Evhen was on anxiety medications and smoking weed to offset the side effects. She says he began vaping in July and about three weeks ago, he got sick. “They were asking him if he ever vaped, have you ever used the vape cartridges? And he said yeah and he was honest about that,” said Smallwood. Evhen’s last Facebook post came after he left the hospital. That same night Evhen left the hospital, he went into cardiac arrest. “He was without a pulse for over a half an hour before they were able to revive him. And he just wasn’t going to wake up from that,” said Smallwood. Thursday, the Tennessee Department of Health confirmed Evhen Cameron died from vaping. TDOH also announced Thursday that vaping-related illnesses had gone up from 49 to 53 cases in the state. https://www.wkrn.com/news/local-news/minnesota-man-identified-as-tennessees-first-vaping-related-death/

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Tonight 11 PM ET Dr. Henry Niman PhDNEW Information About Vaping Crisis Possible Cause Coming Into Focus

Tonight 11 PM ET Dr. Henry Niman PhDNEW Information About Vaping Crisis Possible Cause Coming Into Focus

Tonight 11 PM ET Dr. Henry Niman PhDNEW Information About Vaping Crisis Possible Cause Coming Into Focus

Tonight at 11 PM ET Dr. Henry Niman PhDNEW Information About Vaping Crisis Possible Cause Coming Into Focus

Tennessee Investigation (as of October 17, 2019): 53* lung injury cases associated with e-cigarette use or vaping have been reported to TDH. One death** has been confirmed. Among 53 patients with data on age and sex: 66 percent of patients are male. The median age of patients is 24 years and ages range from 16 to 56 years. 79 percent of patients are under 35 years old. To date, national data suggest that products containing THC, particularly those obtained off the street or from other informal sources (e.g., friends, family members, or illicit dealers), are linked to most of the cases and play a major role in the outbreak. *Case - evidence of respiratory illness, with no other cause identified, and report vaping in the last 90 days. **Death – included in the number of cases https://www.tn.gov/health/cedep/vaping-illness.html

https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html As of October 15, 2019, 1,479* lung injury cases associated with e-cigarette use, or vaping, have been reported to CDC from the District of Columbia, 1 U.S. territory (USVI), and 49 states (all except Alaska). Thirty-three deaths have been confirmed in 24 states: Alabama, California (3), Connecticut, Delaware, Florida, Georgia (2), Illinois, Indiana (3), Kansas (2), Massachusetts, Michigan, Minnesota (3), Mississippi, Missouri, Montana, Nebraska, New Jersey, New York, Oregon (2), Pennsylvania, Tennessee, Texas, Utah, and Virginia. More deaths are under investigation. The median age of deceased patients was 44 years and ranged from 17 to 75 years. Among 1,358 patients with data on age and sex: 70% of patients are male. The median age of patients is 23 years and ages range from 13 to 75 years. 79% of patients are under 35 years old. By age group category: 15% of patients are under 18 years old; 21% of patients are 18 to 20 years old; 18% of patients are 21 to 24 years old; 25% of patients are 25 to 34 years old; and 21% of patients are 35 years or older. To date, national and state data suggest that products containing THC, particularly those obtained off the street or from other informal sources (e.g., friends, family members, or illicit dealers), are linked to most of the cases and play a major role in the outbreak. All patients have a reported history of e-cigarette product use, or vaping, and no consistent evidence of an infectious cause has been discovered. Therefore, the suspected cause is exposure to a chemical or chemicals. The specific chemical exposure(s) causing lung injuries associated with e-cigarette use, or vaping, remains unknown at this time. Among 849 patients with information on substances used in e-cigarette, or vaping, products in the 3 months prior to symptom onset**: About 78% reported using THC-containing products; 31% reported exclusive use of THC-containing products. About 58% reported using nicotine-containing products; 10% reported exclusive use of nicotine-containing products. This complex investigation spans almost all states, involves over a thousand patients, and involves a wide variety of brands and substances and e-cigarette, or vaping, products. Case counts continue to increase and new cases are being reported, which makes it more difficult to determine the cause or causes of this outbreak. Top of Page What CDC is Doing CDC is working 24/7 to identify the cause or causes of this outbreak through partnerships with states and other federal agencies. CDC has activated the Emergency Operations Center (EOC) to coordinate activities and provide assistance to states, public health partners and clinicians around the nation. CDC’s Lung Injury response efforts are committed to: Identify and define the risk factors and the source for lung disease associated with e-cigarette product use, or vaping. Detect and track confirmed and probable cases in the US. Communicate actionable recommendations to state, local, and clinical audiences. Establish lab procedures that can assist with the public heath investigation and patient care. CDC continues to work closely with FDA, states, public health partners, and clinicians on this investigation by providing consultation and technical assistance to states on communication, health alerts, public outreach, and surveillance. CDC is maintaining an outbreak webpage with key messages and weekly updates on case counts, deaths, and resources. CDC is holding congressional briefings, media telebriefings, and regular calls with health departments, clinicians to provide timely updates. CDC worked with states to create primary and out-of-hospital case definitions to classify confirmed and probable cases in a consistent way. States are in the process of classifying patients. We expect that states and clinicians may look back for past lung injury cases based on CDC’s case definition CDC will report numbers of confirmed and probable lung injury cases once states have finalized their classification of cases. By invitation, CDC has deployed Epidemic Intelligence Service (EIS) officers and other CDC staff to support states. CDC is offering additional laboratory testing. CDC is currently validating targeted methods to test chemicals in bronchoalveolar lavage (BAL) fluid, blood, or urine and has received initial samples. CDC is testing pathologic specimens, including lung biopsy or autopsy specimens, associated with patients. CDC is also validating methods for aerosol emission testing of case-associated product samples from e-cigarette, or vaping, products and e-liquids. Initial data from product sample testing has guided the need for these additional assays. Results may provide insight into the nature of the chemical exposure(s) contributing to this outbreak. CDC developed guidance documents for were created to assist public health laboratories, healthcare providers, and pathologists, and others, with specimen collection, storage, and submission. For more information and resources visit For the Public, For Healthcare Providers and For State and Local Health Departments as well as our Publications and Resources page. * The increase in lung injury cases from last week represents both new patients and recent reporting of previously-identified patients to CDC. ** Based on complete reports received. Top of Page Top of Page Dates of symptom onset and hospital admission for patients with lung injury associated with e-cigarette use, or vaping — United States, March 31–October 12, 2019

2019 Respiratory Illnesses in Illinois Cases* Individuals needing more investigation Deaths ** 137 33 1 Updated October 17, 2019 *Case means evidence of respiratory illness, with no other cause identified, and report vaping in the last 90 days. ** Death included in the number of cases Cases in Chicago and Bureau, Cass, Champaign, Cook, DeKalb, DuPage, Fulton, Henry, Kane, Kendall, Knox, Lake, Macoupin, Madison, Marion, McHenry, Peoria, Perry, Rock Island, Sangamon, St. Clair, Tazewell, Vermilion, Wabash, Whiteside, Will, Winnebago, and Woodford counties. Ages - 13-62 years. Median age - 22 years. Updates will be posted by end of day on Thursdays. http://www.dph.illinois.gov/topics-services/prevention-wellness/tobacco/e-cigarettes-and-vapes

Note Ground Glass Opacity in case definition

NASHVILLE (WSMV) - Metro Public Health confirms an adult male is Nashville's first death of severe pulmonary illness associated with the use of electronic cigarettes. MPHD officials are working closely with the Tennessee Department of Health to investigate the recent death. News4 has learned the man was 26-years-old. Officials are still working to determine how long he was emitted to the hospital and how long he was vaping before he became ill. Nashville's deputy director of health believes the victim was vaping for months, however. “Nashville’s first death and reports of severe pulmonary illnesses outbreaks associated with vaping nationwide should be a warning about the risks of severe lung injury from using these products” said Sanmi Areola, Ph.D., Interim Director of the Metro Public Health Department. “We will continue to monitor and investigate reports of illnesses and urge everyone to consider not using e-cigarettes and follow guidance from the CDC.” The Tennessee Department of Health has received reports of 49 cases of serious lung injury among people who use electronic cigarettes or other vaping products. MPHD officials report six of those were Davidson County cases. Officials are still not sure what kind of vaping is making people sick, whether it is THC or nicotine, products bought in a store or off the street. https://www.wsmv.com/news/mphd-first-nashville-vaping-death-was--year-old-male/article_1df15848-f0f1-11e9-ae4d-37e73ebaf2d9.html

As of (10/16/2019) DPH has identified 21 cases of vaping-associated illness in Georgia, including 2 deaths. Other possible cases are being reviewed. Cases range in age from range in age from 18 to 68 years (the median age is 33 years), and 62% are male. Cases experienced severe respiratory symptoms including cough and shortness of breath. Cases also reported experiencing fever, fatigue, chest pain, nausea, vomiting, and diarrhea. Most cases have been hospitalized and have required respiratory support. Cases have reported vaping a variety of substances, including nicotine, THC and CBD products. Clinicians who become aware of cases similar to those described above should report them to the Georgia Poison Center at 1-800-282-5846. https://dph.georgia.gov/vapinglunginjury

References 1. Davidson K , Brancato A , Heetderks P , et al. Outbreak of electronic-cigarette-associated acute lipoid pneumonia—North Carolina, July-August 2019 . MMWR Morb Mortal Wkly Rep. 2019 ; 68 : 784 - 786 . Google Scholar Crossref PubMed 2. Edney A , Wingrove J , Fabian J . Vaping furor intensifies as Trump vows tougher U.S. scrutiny . Bloomberg News . https://www.bloomberg.com/news/articles/2019-09-11/trump-to-hold-meeting-on-vaping-after-reports-of-u-s-illness. Accessed September 13, 2019 . 3. Layden JE , Ghinai I , Pray I , et al. Pulmonary illness related to E-cigarette use in Illinois and Wisconsin—preliminary report [published online September 6, 2019] . N Engl J Med. 4. 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 - 790 . Google Scholar Crossref PubMed 5. Maddock SD , Cirulis MM , Callahan SJ , et al. Pulmonary lipid-laden macrophages and vaping [published online September 6, 2019] . N Engl J Med. 6. Viswam D , Trotter S , Burge PS , et al. Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes . BMJ Case Rep. 2018 : 224350 . 7. McCauley L , Markin C , Hosmer D . An unexpected consequence of electronic cigarette use . Chest. 2012 ; 141 : 1110 - 1113 . Google Scholar Crossref PubMed 8. Katzenstein A-LA. Diffuse alveolar damage. In: Katzenstein A-LA , ed. Katzenstein and Askin’s Surgical Pathology of Non-Neoplastic Lung Disease . 4th ed. Philadelphia, PA : W. B. Saunders ; 2006 : 29 - 31 . 9. Balkisson R , Murray D , Hoffstein V . Alveolar damage due to inhalation of amitrole-containing herbicide . Chest. 1992 ; 101 : 1174 - 1176 . Google Scholar Crossref PubMed 10. Reisz GR , Gammon RS . Toxic pneumonitis from mixing household cleaners . Chest. 1986 ; 89 : 49 - 52 . Google Scholar Crossref PubMed 11. Lilis R , Miller A , Lerman Y . Acute mercury poisoning with severe chronic pulmonary manifestations . Chest. 1985 ; 88 : 306 - 309 . Google Scholar Crossref PubMed 12. Toor AH , Tomashefski JF Jr , Kleinerman J . Respiratory tract pathology in patients with severe burns . Hum Pathol. 1990 ; 21 : 1212 - 1220 . Google Scholar Crossref PubMed 13. Parambil JG , Myers JL , Aubry MC , et al. Causes and prognosis of diffuse alveolar damage diagnosed on surgical lung biopsy . Chest. 2007 ; 132 : 50 - 57 . Google Scholar Crossref PubMed 14. Mukhopadhyay S , Parambil JG . Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS) . Semin Respir Crit Care Med. 2012 ; 33 : 476 - 485 . Google Scholar Crossref PubMed 15. Mukhopadhyay S , Philip AT , Stoppacher R . Pathologic findings in novel influenza A (H1N1) virus (“swine flu”) infection: contrasting clinical manifestations and lung pathology in two fatal cases . Am J Clin Pathol. 2010 ; 133 : 380 - 387 . Google Scholar Crossref PubMed 16. Guarner J , Shieh WJ , Dawson J , et al. Immunohistochemical and in situ hybridization studies of influenza A virus infection in human lungs . Am J Clin Pathol. 2000 ; 114 : 227 - 233 . Google Scholar Crossref PubMed 17. Katzenstein A-LA . Miscellaneous II. Nonspecific inflammatory and destructive diseases. In: Katzenstein A-LA , ed. Katzenstein and Askin’s Surgical Pathology of Non-Neoplastic Lung Disease . 4th ed. Philadelphia, PA : W. B. Saunders ; 2006 : 446 - 447 . 18. Mukhopadhyay S , Mehta AC . Utility of core needle biopsies and transbronchial biopsies for diagnosing nonneoplastic lung diseases . Arch Pathol Lab Med. 2018 ; 142 : 1054 - 1068 . Google Scholar Crossref PubMed 19. Marchiori E , Zanetti G , Mano CM , et al. Lipoid pneumonia in 53 patients after aspiration of mineral oil: comparison of high-resolution computed tomography findings in adults and children . J Comput Assist Tomogr. 2010 ; 34 : 9 - 12 . Google Scholar Crossref PubMed

Discussion The main finding of this case series—one of the first to report lung biopsy findings in vaping-associated pulmonary illness—is that acute lung injury patterns are the most consistent histologic findings in this entity. Other findings include variable numbers of airspace macrophages and varying degrees of interstitial chronic inflammation. Fibrinous exudates within the alveoli, termed acute fibrinous and organizing pneumonia by some authors, are also seen focally in most cases. These findings are nonspecific with regard to etiology but help to confirm the presence of significant lung damage. Lung biopsies are not currently required for the diagnosis of vaping-associated pulmonary illness, but they provide another modality to exclude the possibility of infection. From a histologic standpoint, the two major acute lung injury patterns are DAD and organizing pneumonia.8 It is well known that a wide variety of toxic inhalants can cause acute lung injury, including amitrole-containing herbicides,9 mixtures of household ammonia and bleach,10 chlorine gas, crack cocaine, hydrogen sulfide, mercury vapor,11 nitric acid fumes, nitrogen dioxide, high concentrations of inspired oxygen, paint remover, smoke,12 smoke bombs (ZnCl2), sulfur dioxide, and war gases (phosgene and nitrogen mustard).8 It is plausible, therefore, that inhalation of a potentially toxic mix of chemicals into the lungs (vaping and dabbing) could cause these injury patterns. Such chemicals include flavoring compounds such as diacetyl, 2,3-pentanedione, volatile organic compounds, ultra-fine particles, and heavy metals such as nickel, tin, and lead. Since e-cigarette aerosols can reach high temperatures, it is also conceivable that thermal injury may play a role in some patients. Finally, the fact that all patients in our series—and many in the reported literature—report vaping THC-containing products, rather than nicotine-containing products alone, raises the possibility that THC or a component in THC-containing vape fluid may be implicated in vaping-associated pulmonary illness. The lung biopsy findings described in our cases are not specific for vaping. Both DAD and organizing pneumonia have a long list of potential etiologies, which are only rarely diagnosable on the basis of histologic findings.13,14 Examples of histologically identifiable etiologies of acute lung injury include viral cytopathic changes, fungal organisms, parasites, and aspirated food particles. In contrast, most other etiologies, including toxic inhalants, toxic drugs, aspirated gastric acid, connective tissue diseases, and most viruses, lack pathognomonic pathologic findings.13-16 A pathologic diagnosis of acute lung injury is therefore a mixed blessing. On one hand, it provides strong and helpful evidence of moderate to severe acute injury to the lung and affords a histologic correlate for abnormal imaging findings. On the other hand, it seldom implicates a specific etiologic agent. These principles also apply to vaping-related lung injury. The results of this series strongly suggest that vaping does not cause true exogenous lipoid pneumonia. The label “lipoid pneumonia” has been associated with vaping in several reports based mainly on the presence of oil red O–positive lipid-laden macrophages in BAL fluid.1,5,7 One of the first cases in which oil red O–positive lipid laden macrophages were found was reported by McCauley et al7 in 2012. On this basis, the findings were labeled “exogenous lipoid pneumonia” and attributed to vegetable glycerin used in nicotine solutions, although morphologic features of the macrophages were not illustrated and no lung biopsy was performed. A case study from 2018 reported biopsy findings in a surgical lung biopsy specimen from a patient with suspected vaping-associated pulmonary illness; the biopsy specimen was reported as “suggestive of lipoid pneumonia,” although review of the illustrations does not show classic features of exogenous lipoid pneumonia.6 A more recent series of six cases of vaping-related lung disease from Utah reported oil red O–positive lipid-laden macrophages in BAL fluid. The authors felt that since imaging in these individuals did not show the low attenuation typical of exogenous lipoid pneumonia, these macrophages could not be explained by aspiration of exogenous lipoid material. They hypothesized that these cells might be a useful marker of the disease.5 Similarly, Davidson et al1 labeled their cases of vaping-related lung disease as “acute lipoid pneumonia” based on the presence of oil red O–positive macrophages on BAL in three of five patients. We would like to emphasize that foamy (lipid-laden) macrophages are a common finding in BAL specimens and lung biopsy specimens and are not specific for aspirated or inhaled lipid. There are many potential explanations for their presence, the most common being airway narrowing or obstruction. “Exogenous” causes are less common, the most frequent being inadvertent aspiration of oily substances such as mineral oil–containing laxatives into the lower respiratory tract. The macrophages seen in biopsy specimens from vaping-related lung injury are most similar in morphology to those commonly seen in so-called endogenous lipoid pneumonia, which is not a true entity but merely a nonspecific histologic lesion characterized by the accumulation of foamy (lipid-laden) macrophages with fine intracytoplasmic vacuoles within alveolar spaces.17 The lipid in these cells is derived from cholesterol in the cell membranes of endogenous cells and is presumably phagocytosed by macrophages during clearance of cell debris from the lung. In contrast, exogenous lipoid pneumonia is a well-defined entity characterized by areas of low-attenuation (similar to fat) consolidation on chest CT and macrophages with coarse intracytoplasmic vacuoles on histology, along with frequent involvement of the interstitium by lipid vacuoles surrounded by foreign body–type giant cells.17-19 The difference between macrophage morphology in endogenous lipoid pneumonia and exogenous lipid pneumonia is illustrated in Image 5. With the caveat that our experience is limited, we believe that oil red O staining lacks specificity and is potentially misleading in this setting. However, since this impression is based on only a small number of cases, we do not believe that we are in a position to issue a strong recommendation regarding discontinuation of this stain at this point. A potential area for future studies is to systematically examine the specificity of this stain. Image 5 Open in new tabDownload slide Exogenous vs endogenous lipoid pneumonia. A, Exogenous lipoid pneumonia (for comparison only; not from the current series). Note large coarse vacuoles within macrophage cytoplasm (H&E, ×400). B, Endogenous lipoid pneumonia, case 3. Macrophages are “foamy,” with small fine vacuoles (H&E, ×400). The limitations of this report include the small number of cases and the predominance of transbronchial biopsy specimens. It is conceivable that as more cases are reported, additional pathologic findings will emerge and the histologic spectrum of vaping-related lung injury will widen. It is also possible that examination of surgical lung biopsy specimens or autopsy samples will yield additional histologic information. In summary, lung biopsy specimens from this small series of patients with severe pulmonary disease associated with electronic cigarette product use (vaping) show histologic features of acute lung injury, supporting the contention that inhalation of the aerosol generated by electronic cigarettes (vaping) can cause lung damage

Lung Biopsy Findings The pathologic findings are summarized in Table 2 and illustrated in Image 2, Image 3, and Image 4. All eight biopsy specimens showed acute lung injury, manifesting as organizing pneumonia, diffuse alveolar damage (DAD), unclassifiable organizing acute lung injury, or a combination of these patterns. Four biopsy specimens featured variably prominent areas of organizing pneumonia, characterized by the presence of serpiginous or polypoid fibroblast plugs (Masson bodies) within airspaces (Image 2). This was accompanied by mild interstitial chronic inflammation in three cases and focal acute inflammation within the airspaces in case 8. Two biopsy specimens showed DAD (Image 2). In case 3, the only surgical lung biopsy specimen in this series, areas of DAD were admixed with areas of organizing pneumonia (mixed acute lung injury pattern). Both biopsy specimens with DAD featured hyaline membranes (acute stage of DAD) as well as alveolar septal expansion by fibroblasts (organizing stage of DAD). Two biopsy specimens showed organizing acute lung injury that could not be further classified. Table 2 Pathologic Findings in Vaping-Associated Pulmonary Illness Case No. Biopsy Type Biopsy Site Major Histologic Finding Macrophages in Biopsy Specimen BAL Other Histologic Findings 1 TBBX Right middle lobe, right lower lobe Diffuse alveolar damage, acute and organizing Present within airspaces; no evidence of exogenous lipoid pneumonia BAL cytology: macrophage predominant Fibrinous exudates in airspaces, interstitial chronic inflammation, rare eosinophils; AFB and GMS negative 2 TBBX Lingula and left lower lobe Organizing pneumonia Present within airspaces; no evidence of exogenous lipoid pneumonia No BAL cytology Fibrinous exudates in airspaces, interstitial chronic inflammation, rare eosinophils; GMS negative 3 Surgical (open) lung biopsy Right middle lobe, right lower lobe Diffuse alveolar damage (acute and organizing) and organizing pneumonia Present within airspaces; no evidence of exogenous lipoid pneumonia No BAL cytology Organizing fibrinous exudates, squamous metaplasia 4 TBBX Right lung Organizing acute lung injury Few; no evidence of exogenous lipoid pneumonia Lipid-laden macrophages, oil red O positive Fibrinous exudates in airspaces, interstitial chronic inflammation, AFB and GMS negative 5 TBBX Right lung Organizing pneumonia Present (foamy); no evidence of exogenous lipoid pneumonia Lipid-laden macrophages, oil red O positive Interstitial chronic inflammation, AFB and GMS negative 6 TBBX Right lower lobe Organizing acute lung injury Present (foamy); no evidence of exogenous lipoid pneumonia Lipid-laden macrophages, oil red O positive Fibrinous exudates in airspaces, interstitial chronic inflammation, AFB and GMS negative 7 TBBX Right lower lobe Organizing pneumonia Present (foamy); no evidence of exogenous lipoid pneumonia Macrophage predominant Fibrinous airspace exudates, GMS and AFB negative 8 TBBX Right lower lobe Organizing pneumonia Present (foamy); no evidence of exogenous lipoid pneumonia Macrophage predominant Interstitial inflammation, focal acute inflammation in airspaces, AFB and GMS negative AFB, acid-fast bacteria; BAL, bronchoalveolar lavage; GMS, Grocott methenamine silver; TBBX, transbronchial biopsy. Open in new tab Image 2 Open in new tabDownload slide Lung biopsy findings in vaping-associated pulmonary illness. A, Organizing pneumonia (case 3). A polypoid fibroblast plug fills an airspace (H&E, ×200). B, Organizing pneumonia, case 2 (H&E, ×200). C, Diffuse alveolar damage, case 3. Note hyaline membranes and interstitial thickening (H&E, ×200). D, Diffuse alveolar damage, case 1. Hyaline membranes are beginning to detach into airspaces (H&E, ×200). Image 3 Open in new tabDownload slide Fibrinous exudates and interstitial inflammation in vaping-related lung injury. A, B, Fibrinous exudates within airspaces (A, case 1, H&E, ×200; B, case 3, H&E, ×200). C, Interstitial inflammation, case 1 (H&E, ×200). D, Interstitial inflammatory infiltrate at high magnification, showing lymphocytes and a rare eosinophil (case 2, H&E, ×400). Image 4 Open in new tabDownload slide Macrophages in vaping-related lung injury. A, Foamy macrophages within airspaces, case 3 (H&E, ×400). B, Few intra-alveolar macrophages without distinctive features, case 2 (H&E, ×400). C, Macrophages in bronchoalveolar lavage fluid do not show prominent intracytoplasmic vacuoles (Papanicolaou stain, ×400). D, Oil red O–positive macrophages, case 4, courtesy of Margaret Compton, MD (oil red O, ×400). Fibrinous exudates with varying degrees of organization were noted within airspaces in six of eight biopsy specimens (Image 3). In most cases, they were a focal finding. Overall, interstitial chronic inflammation composed mainly of lymphocytes was noted in six of eight cases. In cases 1 and 8, immunohistochemical stains showed that the lymphocytic infiltrate was composed mainly of CD3-positive T cells and very few CD20-positive B cells. Variable numbers of macrophages were present within airspaces in all cases (Image 4). However, they were not a prominent finding in any biopsy specimen. A CD68 stain (performed in cases 1 and 😎 confirmed the presence of several CD68-positive macrophages, mainly within airspaces. The macrophages contained foamy cytoplasm in three cases, but the coarsely vacuolated cytoplasm characteristic of exogenous lipoid pneumonia was not noted in any of the biopsy specimens. Similarly, interstitial lipid deposits surrounded by multinucleated giant cells—as seen in exogenous lipoid pneumonia—were absent in all cases. BAL fluid was macrophage predominant in six cases, without a foamy appearance or coarse vacuoles. Oil red O staining, performed in cases 4, 5, and 6, was positive in all three cases. The lipid index was 12 in case 4 and 6 in cases 5 and 6. In all biopsy specimens in which special stains for mycobacteria and fungi (Ziehl-Neelsen and/or Grocott methenamine silver) were performed, they were negative. No granulomas or malignant cells were identified, and there were no histologic findings suggesting a plausible alternative etiology.

Results Clinical Findings The clinical findings are summarized in Table 1. All eight patients were men (age range, 19-61 years; mean, 29 years) who developed respiratory symptoms following e-cigarette use (vaping). All patients reported vaping THC; two were also vaping nicotine. One individual had a history of dabbing. The most common presenting symptoms were fever (n = 7/8 patients), cough (n = 6/8), and dyspnea (n = 5/8). Most patients had no significant prior medical illness. One patient had a history of inflammatory bowel disease (case 5). Another had a history of chronic pain (on medical marijuana, tramadol, baclofen, and pregabalin), degenerative disc disease, cervical radiculopathy, peripheral neuropathy, and neurogenic bladder (case 3). Four patients were hypoxic at presentation. Empiric broad-spectrum antibiotics were administered in seven. Bilateral crackles were audible in the lungs on auscultation in two individuals and bilateral coarse rhonchi in one. Notable laboratory findings included leukocytosis (n = 6/8) with neutrophil predominance and elevations in erythrocyte sedimentation rate and C-reactive protein in a few individuals. Workup for infection was negative in seven of eight cases. The tests performed were different for each patient but generally included respiratory viral panels, serologic studies for fungi, testing for Legionella and HIV, and microbiologic cultures of sputum, blood, BAL fluid, and biopsied lung tissue. In case 4, there was a weakly positive Legionella immunoglobulin G, but immunoglobulin M testing and urine antigen were negative. Bronchoscopy with transbronchial lung biopsies were performed in seven patients and surgical lung biopsy in one. There was no clinical or laboratory evidence for other plausible etiologies in any patient; autoimmune serologies were negative in all patients tested. Chest CT showed bilateral ground-glass opacities in all patients Image 1. In addition, bilateral consolidation was noted in some. Seven individuals were treated with corticosteroids and one with antibiotics. Most recovered with corticosteroid therapy and were discharged home within a few days. One patient (61-year-old man, case 3) developed severe acute respiratory distress syndrome. His condition continued to deteriorate, with worsening hypoxia and fever, and his course was complicated by methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia on day 21 of admission. Despite receiving appropriate antibiotic therapy and mechanical ventilation, his condition worsened and he died on day 31 of admission. Table 1 Clinical Features of Patients With Vaping-Associated Pulmonary Illness Variable Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Age, y/sex 35/M 22/M 61/M 20/M 21/M 28/M 19/M 28/M Main symptoms Fever, night sweats, weight loss, dyspnea, cough, nausea, vomiting Fever Dyspnea, cough, chest heaviness, nausea, fever, dizziness Dyspnea, cough, nausea, vomiting, diarrhea, fever Cough, flare of inflammatory bowel disease Dyspnea, cough, fever, nausea Nausea, weight loss, abdominal pain, fever Cough, dyspnea, fever, weight loss, night sweats Substance vaped 90% THC THC (brand: “Dank”) and nicotine; recent refill of cartridge with 90% THC THC/marijuana (vaping) and marijuana wax (dabbing) THC (cannabis oil) Purified THC THC THC, nicotine 93% THC Approximate time between vaping and symptom onset Not known Switched to “Dank” brand a few weeks prior to admission 2 years (vaping) 2 months (dabbing) 2 weeks Simultaneous 3 weeks 14 months Not known Approximate time from symptom onset to presentation 2 days 1 week 3 days 2 weeks 2 weeks 1 week 6 months 3-4 days Initial total leukocyte count, /μL 19,900 9,320 9,000 44,900 12,400 20,000 15,000 13,340 ESR, mm/h 72 102 Not available 123 23 Not available 89 Not available CRP, mg/dL 29.5 35.4 Not available 284 31 Not available 20 Not available Imaging (chest CT) Bilateral GGO and consolidation, peripherally located Bilateral GGO and consolidative opacities in mid to lower lung fields Diffuse bilateral GGO Diffuse bilateral GGO and basilar consolidation Diffuse bilateral GGO Bilateral GGO, somewhat patchy Diffuse bilateral GGO and nodular opacities Diffuse bilateral GGO with solid nodular densities Therapy IV methylprednisolone IV methylprednisolone High-dose IV corticosteroids Corticosteroids Oral prednisone Oral prednisone Antibiotics Antibiotics and methylprednisolone Outcome Alive; discharged home on room air on day 3 of steroids Alive; discharged home on day 3 of treatment Died on day 31 of admission Alive; discharged home on day 7 Alive; discharged home on day 8 Alive; discharged home on day 4 Alive; discharged on room air on day 4 Alive; discharged on room air after 3 days of intravenous methylprednisolone CRP, C-reactive protein; CT, computed tomography; ESR, erythrocyte sedimentation rate; GGO, ground-glass opacities; IV, intravenous; THC, tetrahydrocannabinol. Open in new tab Image 1 Open in new tabDownload slide Chest computed tomography findings in severe pulmonary disease associated with e-cigarette use (vaping). A, Case 1: diffuse bilateral ground-glass opacities with peripheral prominence, mimicking eosinophilic pneumonia. B, Case 2: diffuse bilateral ground-glass opacities with areas of consolidation. C, Case 4: bilateral basilar dependent consolidations with diffuse ground-glass opacities and mild smooth septal thickening. D, Case 6: bilateral ground-glass opacities in a somewhat patchy distribution.

Materials and Methods Eight patients with vaping-associated pulmonary illness who underwent lung biopsies at five separate institutions form the basis of this report (seven transbronchial lung biopsies and one surgical lung biopsy). Cases were included if they fulfilled the CDC surveillance case definition for severe pulmonary disease associated with e-cigarette use.4 All but one case in this series fulfilled CDC criteria for a “confirmed case,” which are as follows: Using an e-cigarette or dabbing during the 90 days before symptom onset Pulmonary infiltrate on chest radiograph or ground-glass opacities on chest computed tomography (CT) Absence of pulmonary infection on initial workup. Minimum criteria include negative respiratory viral panel, influenza polymerase chain reaction, or rapid test if local epidemiology supports testing. All other clinically indicated respiratory infectious disease testing (eg, urine antigen for Streptococcus pneumoniae and Legionella, sputum culture if productive cough, BAL culture if done, blood culture, human immunodeficiency virus (HIV)–related opportunistic respiratory infections if appropriate) must be negative. No evidence in medical record of alternative plausible diagnoses (eg, cardiac, rheumatologic, or neoplastic process) CDC criteria for a “probable case” differ from confirmed cases only in that infection may be identified via culture or polymerase chain reaction, but the clinical team believes this is not the sole cause of the underlying respiratory disease process. One case in this report fulfilled criteria for a probable case (case 4).

“Vaping” refers to inhalation of the aerosol produced by electronic cigarettes (e-cigarettes, or electronic vaporizers). This aerosol is generated by heating a liquid that usually contains nicotine, flavorings, and other chemicals.1 E-cigarettes can also be used to deliver marijuana and other drugs. A variation on this theme is “dabbing,” which involves inhalation of an aerosol formed by superheating substances that contain high concentrations of tetrahydrocannabinol (THC) and other plant compounds such as cannabidiol. In the recent past, lung disease related to vaping has emerged as a public health issue in the United States, generating considerable attention in the national news media.2 A recent report in the New England Journal of Medicine described the clinical features of a series of 53 patients from Illinois and Wisconsin with vaping-related pulmonary illness.3 This report was a major addition to the literature documenting a link between vaping and lung disease. At the time of this writing (September 2019), 530 possible cases of acute lung injury potentially associated with vaping have been reported from 38 states.1,4 The Centers for Disease Control and Prevention (CDC) has released interim guidelines on case definitions (discussed in detail in the Materials and Methods section).4 Despite the intense spotlight on vaping, the pathologic findings of vaping-related lung disease have not been adequately described. A few reports have appended labels to the lung injury patterns observed in these patients based on imaging and/or bronchoalveolar lavage (BAL) findings, but biopsy findings remain largely unknown.1,5-7 The aim of this report is to describe and illustrate the histopathologic features of lung disease attributable to vaping.

Abstract Objectives The aim of this report is to describe the lung biopsy findings in vaping-associated pulmonary illness. Methods Lung biopsies from eight patients with vaping-associated pulmonary illness were reviewed. Results The biopsies were from eight men (aged 19-61 years) with respiratory symptoms following e-cigarette use (vaping). Workup for infection was negative in all cases, and there was no evidence for other etiologies. Imaging showed diffuse bilateral ground-glass opacities in all patients. Most recovered with corticosteroid therapy, while one died. Lung biopsies (seven transbronchial, one surgical) showed acute lung injury, including organizing pneumonia and/or diffuse alveolar damage. Common features were fibroblast plugs, hyaline membranes, fibrinous exudates, type 2 pneumocyte hyperplasia, and interstitial organization. Some cases featured a sparse interstitial chronic inflammatory infiltrate. Although macrophages were present within the airspaces in all cases, this feature was not prominent, and findings typical of exogenous lipoid pneumonia were absent. Conclusions The histopathology of acute pulmonary illness related to e-cigarette use (vaping) is characterized by acute lung injury patterns, supporting the contention that vaping can cause severe lung damage.

Number of Reported Cases of Severe Lung Injury Associated with E-Cigarette Use or Vaping, Oklahoma Number of new confirmed or probable cases between 10/10/2019 and 10/16/2019 Cumulative number of confirmed or probable cases Number of new confirmed or probable deaths between 10/10/2019 and 10/16/2019 Cumulative number of confirmed or probable deaths 0 4 0 0 Case details Of the four patients, One is under the age of 18, two (50%) are 18 to 34 years of age, and one is 35 years of age or older. Patients are residents of: Oklahoma County (2), Tulsa County (1), and the Northeast region of the state (1). https://www.ok.gov/health/Prevention_and_Preparedness/Injury_Prevention_Service/Vaping-related_Lung_Injury/index.html