Electronic-cigarette Or Vaping Product Use-associated Lung Injury Research Articles

Vaping lung damage (review)

The review presents data from meta-analyses and original studies on the study of the vapers disease electronic cigarette or vaping product use-associated lung injury (EVALI) a new nosological form in patients with acute and subacute respiratory diseases caused by the consumption of electronic nicotine delivery vehicles, or vaping. The number of users are growing in around the world, especially among young people. According to a 2022 meta-analysis, the global prevalence of vaping use was 23%, including 16% in women and 22% in men. Prevalence of electronic nicotine delivery systems among cigarette smokers reached 43%, while on different continents, except for Asia, during the life it was approximately the same: in America 24%, Europe 26%, Asia 16%, Oceania 25%. Vaping rates among children aged 15 to 17 are almost four times (21.3%) higher than those aged 1214 (5.4%). Two-thirds (66.1%) of children aged 12 to 17 using electronic nicotine delivery devices were also smokers, while they started with vapes. Nicotine cartridges used by 89.3% of teen vapers aged 15 to 19 years. Vaping lung diseases have been reported since invention e-cigarettes, but the number of cases increased sharply at the end of September 2019, and by February In 2020, the number of hospitalized patients in the United States reached 2807, with 68 confirmed deaths. Most of the cases are male adolescents and men aged 1334 years. The review discusses the etiology, clinical picture, imaging findings, pathological EVALI features. When examining patients with EVALI, computed tomography revealed images characteristic of acute lung injury and pneumonia, as well as those resembling non-fibrous hypersensitivity pneumonitis, acute eosinophilic pneumonia. The article discusses the main differences between these diseases and the computed tomography picture of COVID-19. Before EVALI, vaping was associated with a wide range of pulmonary manifestations, including lipoid pneumonia, acute respiratory distress syndrome and diffuse alveolar hemorrhage. Although the overall prevalence of EVALI has declined sharply compared to with a peak in September 2019, other chemicals may appear that cause various pulmonary diseases associated with vaping. EVALI is a new nosological form in patients with acute and subacute respiratory diseases caused by lung damage due to the use of electronic means delivery of nicotine. The appearance of radiographic images in EVALI is diverse: from bilateral opacities in the lungs to reveal centrilobular nodules resembling non-fibrous hypersensitivity pneumonitis. When interpreting acute lung injury in young people, the possibility of EVALI should be considered.

Bronchoalveolar Lavage (BAL) and Pathologic Assessment of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): The EVALI-BAL Study, A Multicenter Cohort.

E-cigarette or vaping-use related acute lung injury (EVALI) is a spectrum of radiographic and histologic patterns consistent with acute to subacute lung injury. However, limited data exist characterizing bronchoalveolar lavage (BAL) findings. The goal of this study is to further define the pathologic findings from BAL and biopsy samples of subjects with EVALI across 7 institutions. A multicentered registry of patients admitted with EVALI who underwent flexible bronchoscopy with BAL+/-transbronchial biopsy from July 2019 to April 2021 was compiled for retrospective evaluation from 7 academic institutions throughout the United States. Radiographic and cytopathologic findings and frequencies were correlated with the substance vaped. Data from 21 subjects (42.9% women) who were predominantly White (76.2%) with a median age of 25 years (range, 16 to 68) with EVALI were included in this study. Sixteen patients (76.2%) reported use of tetrahydrocannabinol; the remainder used nicotine. BAL was performed in 19 of the 21 subjects, and transbronchial lung biopsy was performed in 7 subjects. BAL findings revealed neutrophilic predominance (median, 59.5%, range, 3.1 to 98) in most cases. Ten BAL samples demonstrated pulmonary eosinophilia ranging from 0.2% to 49.1% with one subject suggesting a diagnosis of acute eosinophilic pneumonia associated with the use of e-cigarettes. Lipid-laden macrophages were noted in 10 of 15 reports (66.7%). Transbronchial biopsy most frequently demonstrated patterns of organizing pneumonia (57.1%). EVALI-associated BAL findings typically demonstrate a spectrum of nonspecific inflammatory changes, including neutrophilia, lipid-laden macrophages, and in some cases eosinophilia.

E-cigarette or vaping product use-associated lung injury: A review of clinico-radio-pathological characteristics.

Aggressive, albeit false marketing of electronic nicotine delivery systems (ENDS) or vaping devices as safer alternatives to cigarette smoking, combined with lack of regulations, has led to its mass adoption, especially among youth. A sudden increase in acute lung injuries was noted in 2019 which was linked to ENDS. It was termed by the Centers for Disease Control and Prevention (CDC) as electronic cigarette or vaping product use-associated lung injury (EVALI). Analysis of bronchoalveolar lavage fluid samples linked EVALI to vitamin E acetate (VEA), which is used as a diluting agent for marijuana oils. Patients with EVALI present with a combination of non-specific respiratory, gastrointestinal, and systemic symptoms. Laboratory results may show elevated inflammatory biomarkers. EVALI is a diagnosis of exclusion and must meet the following criteria: i) history of vaping within last 90 days, ii) abnormal chest imaging, iii) negative evaluation for infection, and iv) no other plausible diagnosis. A spectrum of computed tomography (CT) chest findings has been reported in EVALI, ranging from diffuse alveolar damage to organizing pneumonia, characterized by bilateral ground-glass opacities, consolidation, and septal thickening. A similar spectrum is seen on histopathology, characterized by lipid-laden alveolar macrophages, with varying degrees of infiltrative inflammatory cells and fibrin deposition. Early and accurate identification of the EVALI pattern can help optimize patient care. For example, in diffuse alveolar damage (DAD), a lower threshold for ventilation support and corticosteroid may improve outcomes. Here, we review the etiopathogenesis, clinical management, histopathology, and imaging features of EVALI.

Role of cannabinoids and vitamin E analogues in macrophages foam cells formation

Recently, macrophages foam cells have gained attention in cases of electronic‐cigarette or vaping product use‐associated lung injury (EVALI). An increased number of foam cells was detected in bronchoalveolar lavages and lungs after inhaling e‐cigarette smoke from products containing cannabinoids and the vitamin E analogue, alpha‐tocopherol acetate (αTA), that was present as vape‐cartridge additive. Increased levels of intact αTA are reportedly detected in EVALI indicating that conversion of αTA to αT may less occur in lungs upon inhaling vapors from e‐cigarettes containing αTA.HypothesisWhereas the molecular mechanisms by which macrophages foam cells are formed after vaping are unclear, it appears possible that cannabinoid receptors play a role, as lung‐resident macrophages express cannabinoid receptors. Dysregulation of cannabinoid receptors by αTA and cannabinoids may induce the CD36 scavenger receptor/fatty acids transporter (CD36/FAT) and/or reduce the ATP binding cassette transporters A1 and G1 (ABCA1/G1) expression leading to lipid accumulation. Therefore, we analyzed the regulatory effects on lipid homeostasis of natural alpha‐tocopherol (RRR‐αT), natural RRR‐αTA (αTAn) and synthetic racemic all‐rac‐αTA (αTAr) with and without co‐treatment with cannabinoids (cannabinol (CBD), Δ9‐tetrahydrocannabinol (THC)) in THP‐1 monocytes and macrophages (differentiated for 48 h with 100 ng/ml phorbol‐12‐myristate‐13‐acetate (PMA)).ResultsQuantification of lipids in macrophages indicated that more lipids accumulate with αT, less with αTAn and αTAr, whereas control alpha‐tocopheryl phosphate (αTP) clearly inhibited. Co‐treatment with THC increased lipid accumulation with αT, αTAn as well as with CBD, whereas αTP again clearly inhibited. In THP‐1 monocytes, CD36 scavenger receptor was stimulated with αTAn and THC and with co‐treatment with THC and αTAn or CBD. In THP‐1 macrophages, CD36 was only up‐regulated by CBD and co‐treatment with αTAn or αTAr reduced it. In THP‐1 monocytes, cell cycle progression was only affected by CBD (increased G1, decreased S) and co‐treatment with αTAn and αTAr restored it. In macrophages, no significant toxicity was measured with lactate dehydrogenase (LDH) release assay by these treatments at 24 h, 48 h and 72 h at αTA concentrations below 50 μM.SummaryAlthough the mechanisms by which intact αTA may affect lungs in cases of EVALI are still unclear it may disrupt the pulmonary surfactant, act as linactant, and/or dysregulate lipid homeostasis and contribute to formation of macrophages foam cells and inflammation. Lipid accumulation in monocytes/macrophages and foam cells formation were modulated by cannabinoids and αTA but the involvement of lipid homeostasis genes such as CD36/FAT and ABCA1/G1 remains to be further elucidated. A detailed analysis of the molecular mechanisms by which foam cells are formed will not only be important to understand EVALI but also for atherosclerosis and non‐alcoholic steatohepatitis (NASH).

102 Vaping of Vitamin E Acetate Causes Acute Lung Injury in a Dose-dependent Manner in Sheep

IntroductionThe Centers for Disease Control and Prevention and the Food and Drug Administration have reported an increasing number of clinical cases of pulmonary injury following the use of e-cigarette/vaping products. Although the causative factors for the national outbreak of electronic-cigarette, or vaping product use-associated lung injury (EVALI) has not been established, CDC reported that vitamin E acetate (VEA) is strongly linked to the EVALI outbreak. In this study, we tested the hypothesis that VEA vaping causes acute lung injury in a dose-dependent manner in a sheep model.MethodsSheep were surgically prepared under anesthesia and analgesia with multiple vascular catheters (pulmonary arterial, left atrial, and femoral arterial). To assess pulmonary edema, the mediastinal lymph node vessel draining the lung was cannulated. After a 5-day surgical recovery, a tracheostomy tube and urinary catheter were placed. Then, the sheep were placed on a mechanical ventilator and VEA vaping was immediately started in the following groups: (1) vaped with glycerol (n=1); (2) vaped with 0.4mg of VEA (n=2); (3) vaped with 0.6mg of VEA (n=1); (4) vaped with 0.8mg of VEA (n=7); and (5) not injured, not treated (Sham, n=6). Sheep were resuscitated with lactated Ringer’s solution (4mL/kg/hr). Sheep in a conscious state was monitored with 4 hrs intervals for cardiopulmonary variables for 48 hrs.ResultsPulmonary gas exchange, represented by the PaO2/FiO2 ratio, was unchanged in sham, glycerol, and 0.4 mg VEA groups. In the 0.6 VEA group, the PaO2/FiO2 ratio was decreased from 42 to 48 hrs, while in the 0.8 mg VEA group, it was strongly decreased starting at 24 hrs and remained low throughout the remaining period. Lung lymph flow, an index of pulmonary microvascular permeability, was increased more than 2-fold in 0.6 and 0.8 mg VEA groups. Lung compliance also tended to decrease in all VEA groups.ConclusionsVEA vaping causes acute lung injury in a dose-dependent manner in sheep. Further studies should investigate underlying mechanistic aspects that cause increased microvascular permeability.

Aerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages.

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. We used mass spectrometry to evaluate the composition of aerosolized VEA condensate and the VEA deposition in murine or human alveolar macrophages. Extended vaping for 28 days versus 15 days did not worsen lung injury but caused systemic inflammation in the murine EVALI model. Vaping plus influenza increased lung water compared with virus alone. Murine alveolar macrophages exposed to vaped VEA hydrolyzed the VEA to vitamin E with evidence of oxidative stress in the alveolar space and systemic circulation. Aerosolized VEA also induced cell death and chemokine release and reduced efferocytotic function in human alveolar macrophages in vitro. These findings provide new insights into the biological mechanisms of VEA toxicity.

Clinical Features of E-cigarette, or Vaping, Product Use–Associated Lung Injury in Teenagers

The authors described the spectrum of disease seen in patients admitted with electronic cigarette or vaping product-use–associated lung injury (EVALI). This is the first focused case series of EVALI in children.All patients aged 13 to 18 years admitted to the authors’ tertiary care, university-affiliated children’s hospital (Dallas, TX) with a diagnosis of EVALI.This was a retrospective chart review of patients admitted with EVALI from December 2018 to November 2019.A total of 13 patients were admitted with EVALI. Patients endorsed usage of δ-9-tetrahydrocannabinol (THC) (12), nicotine and THC (7), and nicotine (1). Symptoms included subjective fever (100%), respiratory symptoms (85%), and GI symptoms (85%). A total of 23% of abnormal lung CTs were identified on abdominal computed tomography scans in patients undergoing a primary gastrointestinal evaluation. Respiratory support included room air (1), nasal cannula (8), bilevel positive airway pressure (2), intubation (1), and venovenous extracorporeal membrane oxygenation (1). Four patients required supplemental oxygen at discharge. Five patients had pulmonary function tests pre- and postglucocorticoid administration. forced expiratory volume in 1 second and forced vital capacity both increased significantly after glucocorticoids.The clinical severity of EVALI in adolescents is variable. The majority of admitted patients required some form of oxygenation support. Glucocorticoids were a successful treatment with objective improvement in pulmonary function tests postglucocorticoid administration.This is an important case series for pediatricians to learn from, regarding EVALI. As we learn more about this potentially fatal condition, common threads have emerged that are supported by these findings, including the use of vaping products for THC and various alterations to the vaping device. It is important for pediatricians and all health care professionals who work with adolescents to recognize the dangers associated with vaping and e-cigarette use as well as learn skills to communicate these risks with individual patients. Although federal and state regulations have been enacted to try and limit the use of these products in children and adolescents, millions remain vulnerable.

A SINGLE ODDITY: EVALI OF THE UNILATERAL LUNG

TOPIC: Tobacco Cessation and Prevention TYPE: Medical Student/Resident Case Reports INTRODUCTION: The United States is in an epidemic of electronic cigarette or vaping product use-associated lung injury (EVALI) which is characterized by a combination of respiratory, constitutional and gastrointestinal symptoms1. The most common presenting signs and symptoms include dyspnea, cough, fever, tachypnea, tachycardia, hypoxia, malaise, and emesis2. Two predominant patterns of acute lung injury have been recognized in EVALI: Diffuse Alveolar Damage and Organizing Pneumonia. Radiographic findings in the literature for patients diagnosed with EVALI include a pattern of bilateral and symmetric ground glass opacities with subpleural and areas of lobular sparing3. We present a unique case of severe EVALI isolated to a single lung that has not been documented in the literature and was managed conservatively. CASE PRESENTATION: A 36-year-old male with a history of vaping nicotine products presented with acute onset of dyspnea, hypoxia and tachycardia. Prior to switching to vaping, he admitted to a 7 pack-year smoking history of cigarettes. He endorsed using a Juul© vaping device for two years before switching to another product, Fume©, for 2 months prior to presentation. On physical exam, the patient was tachypneic and in severe respiratory distress with crackles in the right lung. Vital signs were significant for a heart rate of 129 and oxygen saturation of 90% on ambient air. COVID PCR and viral respiratory panel testing were negative. CT of the chest showed diffuse right sided nonspecific reticulonodular pattern with some bronchiectatic changes. Our patient requested conservative management due to financial concerns. Thus we elected to treat without antibiotics and systemic steroids. Supportive treatment included bronchodilators and supplemental oxygen. He improved clinically over the next five days despite our unusual conservative approach. A repeat CT of the chest at that time showed marked interval resolution of radiographic findings. DISCUSSION: Our case highlights that clinicians must be able to recognize that unilateral organizing pneumonia in the setting of recent vaping can be a manifestation of EVALI. Anecdotal literature supports the use of systemic glucocorticoids but an exact treatment of EVALI is not yet known1. The approach in our patient with significant hypoxia and radiographic lung involvement reinforces that supportive treatment of EVALI, as opposed to aggressive measures with empiric antibiotics and systemic glucocorticoids, can lead to similar outcomes without the risk of adverse effects of those medications. CONCLUSIONS: A conservative approach can likely decrease financial burdens for patients and medical institutions and still yield positive medical results. Further longitudinal research is required to determine the benefit of empiric treatment of EVALI and radiographic studies to database future unilateral presentations of EVALI. REFERENCE #1: Werner AK, Koumans EH, Chatham-Stephens K, et al. Hospitalizations and Deaths Associated with EVALI. The New England Journal of Medicine 2020;382;1589-98. REFERENCE #2: Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin - preliminary report. N Engl J Med 2019;382:903-916. REFERENCE #3: Kligerman S, Raptis C, Larsen B, et al. Radiologic, Pathologic, Clinical and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions. Radiology 2020;294: 491-505 DISCLOSURES: No relevant relationships by MARIA CANIZARES-OTERO, source=Web Response No relevant relationships by Benjamin Carmel, source=Web Response No relevant relationships by Vijay Srinivasan, source=Web Response No relevant relationships by Hector Vazquez Saad, source=Web Response

BILATERAL SPONTANEOUS PNEUMOTHORAXES ASSOCIATED WITH VAPING

TOPIC: Tobacco Cessation and Prevention TYPE: Medical Student/Resident Case Reports INTRODUCTION: Electronic cigarette or vaping product use associated lung injury (EVALI) has received increasing attention by the Centers for Disease Control and Prevention (CDC) within the last year due to a recent increase of cases of acute lung injury associated with vaping. The CDC has established criteria for EVALI: 1) the patient must have vaped within 90 days prior to symptom onset;2) there is evidence of pulmonary infiltrate on chest radiographs or chest CT;3) absence of pulmonary infection on initial work-up;4) no evidence alternative diagnoses.Spontaneous pneumothoraces (SPs) are often idiopathic in nature, classically in tall, thin males between the ages of 15-34 years old, as well as underlying lung or connective tissue diseases. There are few reported cases of SPs in association with vaping or e-cigarette use, with bilateral pneumothoraces being nearly unseen. CASE PRESENTATION: A 26-year-old Caucasian male with past medical history of polysubstance abuse presented to the emergency department with a one-day history of shortness of breath and chest pain. He was an active daily vaper. On arrival, he endorsed dyspnea, hemoptysis, presyncope, and pleuritic pain. Vitals showed hypotension, tachycardia, and tachypnea. Physical exam shows no trauma or tracheal deviation. Lung sounds were decreased at both apices. Chest X-ray showed bilateral apical pneumothoraces. Workup for respiratory virus panel and COVID were negative. CBC and CMP lab values were largely unremarkable, only with lactic acidosis to 4.4 mmol/L. Toxicology was positive for cocaine, THC, and opiates. A left sided thoracostomy was performed, resulting in resolution of the left sided pneumothorax. Shortly after placement, the patient traumatically removed his thoracostomy tube. 100% oxygen resulted in resolution of the right sided pneumothorax. The patient was downgraded from the ICU and discharged on hospital day three with resolution of symptoms. DISCUSSION: Spontaneous pneumothorax is a potentially life-threatening emergency condition. This patient's concerning presentation with spontaneous bilateral secondary pneumothoraces (SBSP) and multifocal opacities on the chest x-ray in the setting of vape use, without a prior or family history of lung disease, created a concerning clinical picture. EVALI is already a concerning condition. Per the CDC as of January 14, 2020, there were 2,668 cases of EVALI requiring hospitalization, with 68 cases resulting in mortality CONCLUSIONS: This case is highlighted in order to add to increasing evidence of the dangerous effects of vaping. Patients should be counseled on the wide variety of risks of vaping. Furthermore, cases of SBSP are quite rare, and this patient's history makes vaping and marijuana use the most likely contributing factors to his presentation. Patients with a history of spontaneous pneumothorax should be monitored over time for recurrences and counseled on vaping cessation. REFERENCE #1: Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html REFERENCE #2: Graf-Deuel E, Knoblauch A: Simultaneous bilateral spontaneous pneumothorax. Chest. 1994, 105:1142-1146. 10.1378/chest.105.4.1142 DISCLOSURES: No relevant relationships by Riley Ewen, source=Web Response No relevant relationships by Gilad Guez, source=Web Response no disclosure on file for Brijesh Patel;no disclosure on file for Farhan Shah;

VAPING CAN BREAK YOUR HEART

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Electronic cigarette or vaping product use-associated lung injury (EVALI) is potentially life-threatening disease that has become increasingly recognized over the last years. However, the extra-pulmonary manifestations of this disease are not as well described. We present a patient who simultaneously developed acute EVALI and stress induced cardiomyopathy. CASE PRESENTATION: A 35-year-old female with a recent heavy vaping history presented to hospital via EMS due to disorganized behavior. Her past medical history was notable for polysubstance abuse and an extensive neuropsychiatric history. Her vital signs were notable for sinus tachycardia, hypotension and hypoxia with an oxyhemoglobin saturation 65%. Her physical exam was notable for cyanosis, rales to pulmonary auscultation and use of accessory muscles. She was intubated and started on empiric antibiotics for community acquired pneumonia, and vasopressors. A computer tomography pulmonary angiography (CTPE) was negative for acute pulmonary embolism but showed scattered bilateral airspace opacities with dependent consolidations (fig 1.). Relevant laboratory on admission included procalcitonin 28.17, WBC count 12.9 and troponin 1.58. SARs-COV-2, serum blood cultures, legionella antigen, streptococci pneumoniae antigen and HIV were negative. Urine toxicology was positive for cannabinoids. Bronchoalveolar lavage later demonstrated 50,000 TNC with neutrophil predominance. EKG showed sinus tachycardia and nonspecific ST depression. Echocardiogram revealed severe diffuse hypokinesis with left ventricular ejection fraction (LVEF) of 13%. During her ICU course she continued on mechanical ventilation with lung protective strategy, systemic glucocorticoids and antibiotics. Vasopressors were subsequently weaned off. Repeated echocardiogram on ICU day five demonstrated a recovered LVEF at 55%. Patient's hypoxemia improved, and she was successfully extubated on ICU day eight. DISCUSSION: Pulmonary injury is the most well described clinical manifestation of EVALI, however a large majority of these patients also present with gastrointestinal symptoms and malaise, suggesting a systemic disease process. Our patient had newly reduced LVEF suggestive of stress induced cardiomyopathy which consequently improved with standard and supportive care. CONCLUSIONS: It is important to maintain a high index of suspicion of secondary organ damage, as prompt diagnosis and treatment of EVALI associated cardiac dysfunction can have an impact in short- and long-term prognosis. REFERENCE #1: Kligerman S, Raptis C, Larsen B, Henry TS, Caporale A, Tazelaar H, Schiebler ML, Wehrli FW, Klein JS, Kanne J. Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions. Radiology. 2020 Mar;294(3):491-505. doi: 10.1148/radiol.2020192585. Epub 2020 Jan 28. PMID: 31990264. DISCLOSURES: No relevant relationships by David barounis, source=Web Response No relevant relationships by Xavier Fonseca, source=Web Response No relevant relationships by Dana Mueller, source=Web Response

Adolescent perceptions of E-cigarette use and vaping behavior before and after the EVALI outbreak

This study sought to determine whether adolescents' e-cigarette risk perceptions, perceived benefits, and positive expectations, and vaping behavior changed after the electronic-cigarette or vaping product use-associated lung injury (EVALI) outbreak. This longitudinal survey studied 1539 high school students in suburban Philadelphia, PA in 11th and 12th grade, before and after the outbreak of EVALI cases in 2019. Adolescents who reported current nicotine vaping at baseline (versus those who did not) had a greater increase in risk perceptions (B = −0.31, p = 0.04) and a greater decrease in positive expectations (B = −1.30, p = 0.003) at follow-up. Adolescents who reported current marijuana vaping at baseline (versus those who did not) had greater perceived benefits (B = 2.19, p < 0.001), lower risk perceptions (B = 0.39, p < 0.001), and greater positive expectations of e-cigarette use (B = 1.43, p < 0.001) across time. Odds of current nicotine vaping at follow-up increased (OR = 1.61, 95% CI = 1.08, 2.41) for adolescents who maintained lower risk perceptions. Odds of current nicotine vaping at follow-up decreased (OR = 0.33, 95% CI = 0.21, 0.50) for adolescents whose positive expectations of e-cigarette use decreased. The odds of current marijuana vaping at follow-up decreased (OR = 0.64, 95% CI = 0.42, 0.98) for adolescents whose positive expectations of e-cigarette use decreased. Perceptions of the risks of e-cigarette use increased and positive expectations of e-cigarette use decreased after the EVALI outbreak. Adolescent risk perceptions and positive expectations of e-cigarette use are two potential targets to impact vaping behavior. Emphasizing the risks of e-cigarette use while decreasing positive expectations of use have the potential to reduce vaping behavior, and perhaps subsequent EVALI cases.

M409 ELECTRONIC CIGARETTE OR VAPING PRODUCT USE-ASSOCIATED LUNG INJURY AMIDST THE COVID-19 PANDEMIC

Electronic cigarette or vaping product use-associated lung injury (EVALI) is currently a diagnosis of exclusion. Given the pro-inflammatory and partly immune-mediated pathogenesis, EVALI and SARS-CoV-2 infection share several clinical features, potentially posing a diagnostic challenge. A 24-year-old man without significant medical history presented with fever, worsening cough, dyspnea, vomiting and diarrhea during a local peak of COVID-19 cases. He required 10 liters of supplemental oxygen due to hypoxemic respiratory failure. Laboratory workup revealed: leukocytosis (ANC 15,200 cells/microliter), elevated ESR/CRP, ferritin-1030 ng/mL, d-dimer-791 ng/mL, procalcitonin-0.8 ng/mL, mild transaminitis, elevated IL-6 (173 pg/mL). Six nasopharyngeal PCR assays did not detect SARS-CoV-2 (2 prior to admission). Chest computed tomography delineated diffuse patchy ground glass opacities with shotty mediastinal and hilar lymphadenopathy. The working diagnosis was COVID-19 disease, however the patient subsequently admitted to frequent vaping of cannabis and THC-oils. He clinically improved after receiving antibiotics and steroids for treatment of EVALI. Similar to COVID-19, EVALI has a broad spectrum of pulmonary findings and may be accompanied by gastrointestinal or constitutional manifestations, elevated inflammatory markers and non-specific imaging. Leukocytosis with neutrophilic predominance is found in EVALI. The proposed immunopathology of lung damage in EVALI is via a cytokine cascade of IL-1, IL-6, and IL-13. COVID-19 may portend a detrimental cytokine storm syndrome. Elevated peripheral IL-6 levels can be detected in both diseases; this patient had a markedly elevated level suggesting a cytokine storm-like picture. The overall features of this case suggested EVALI, illustrating the importance of its consideration in the differential diagnosis of SARS-CoV-2 infection.

LIPID LADEN MACROPHAGES IN E-CIGARETTE OR VAPING PRODUCT USE-ASSOCIATED LUNG INJURY

SESSION TITLE: Medical Student/Resident Tobacco Cessation and Prevention Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Electronic-cigarette or vaping, product use-associated lung injury (EVALI) was first reported to the CDC in August 2019 and has to lead to a significant number of hospitalizations and deaths [1]. Various patterns of acute lung injury including diffuse alveolar damage, acute fibrinous pneumonitis, and organizing pneumonia have been described in association with EVALI [2]. However, the presence of lipid-laden macrophages in BAL has been consistently noted in some series of EVALI [3]. Here, we present a unique case of EVALI in which a very high number of lipid-laden macrophages were noted. CASE PRESENTATION: A 44-year-old man who had been vaping nicotine and THC regularly presented with progressively worsening dyspnea. He was febrile, tachycardic, tachypneic and hypoxemic upon presentation. Computed tomography of the chest revealed multi-focal bilateral hazy ground-glass opacities with subpleural sparing and inter-lobular septal thickening. He underwent flexible bronchoscopy for further evaluation. Bronchoalveolar lavage (BAL) showed a high number of lipid-laden macrophages on the oil-red-O stain with a Colombo count over 200. He was started on systemic corticosteroids for presumed EVALI resulting in significant improvement of his condition. He was discharged home in stable condition on day 6 of admission. DISCUSSION: A total of 2,807 hospitalized EVALI cases with 68 reported deaths have been confirmed by the Centers for Disease Control and Prevention in the United States with a majority of cases being associated with tetrahydrocannabinol containing products. Radiographic abnormalities of interlobular septal thickening along with bilateral hazy ground-glass opacities have been described with this condition and histopathological features include acute fibrinous pneumonitis, diffuse alveolar damage, lipoid pneumonia and organizing pneumonia. Lipid-laden macrophages in BAL fluid have been noted in many patients with EVALI but the significance of lipid-laden macrophages in diagnosing this condition remains unclear. However, the presence of lipid-laden macrophages in a patient with a history of electronic-cigarette or vaping product use and no evidence of infection should strongly suggest a diagnosis of EVALI. To our knowledge, no previous case with such a high number of lipid-laden macrophages has been reported. CONCLUSIONS: A rapid identification tool for EVALI is required given the current outbreak. The presence of lipid-laden macrophages in the BAL fluid may serve as such a marker in the appropriate clinical setting. Prompt treatment with systemic corticosteroids should be considered once lipid-laden macrophages are identified in patients with a history of vaping. Reference #1: Perrine CG, Pickens CM, Boehmer TK, et al. Characteristics of a Multistate Outbreak of Lung Injury Associated with E-cigarette Use, or Vaping - United States, 2019 [published correction appears in MMWR Morb Mortal Wkly Rep. 2019 Oct 11;68(40):900]. MMWR Morb Mortal Wkly Rep. 2019;68(39):860-864. Published 2019 Oct 4. doi:10.15585/mmwr.mm6839e1 Reference #2: Butt YM, Smith ML, Tazelaar HD, et al. Pathology of Vaping-Associated Lung Injury. N Engl J Med. 2019;381(18):1780-1781. doi:10.1056/NEJMc1913069 Reference #3: Maddock SD, Cirulis MM, Callahan SJ, et al. Pulmonary Lipid-Laden Macrophages and Vaping. N Engl J Med. 2019;381(15):1488-1489. doi:10.1056/NEJMc1912038 DISCLOSURES: No relevant relationships by Moeezullah Beg, source=Web Response No relevant relationships by Mahnoor Mir, source=Web Response No relevant relationships by Jay Peters, source=Web Response

Does 'Dry Hit' vaping of vitamin E acetate contribute to EVALI? Simulating toxic ketene formation during e-cigarette use.

Vitamin E acetate (VEA) is strongly linked to the outbreak of electronic-cigarette or vaping product use-associated lung injury (EVALI). It has been proposed that VEA decomposition to ketene–a respiratory poison that damages lungs at low ppm levels–may play a role in EVALI. However, there is no information available on the temperature at which VEA decomposes and how this correlates with the vaping process. We have studied the temperature-dependent kinetics of VEA decomposition using quantum chemical and statistical mechanical modelling techniques, developing a chemical kinetic model of the vaping process. This model predicts that, under typical vaping conditions, the use of VEA contaminated e-cigarette products is unlikely to produce ketene at harmful levels. However, at the high temperatures encountered at low e-cigarette product levels, which produce ‘dry hits’, ketene concentrations are predicted to reach acutely toxic levels in the lungs (as high as 30 ppm). We therefore hypothesize that dry hit vaping of e-cigarette products containing VEA contributes to EVALI.

Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate.

Electronic-cigarette, or vaping, product use-associated lung injury (EVALI) is a syndrome of acute respiratory failure characterized by monocytic and neutrophilic alveolar inflammation. Epidemiological and clinical evidence suggests a role of vitamin E acetate (VEA) in the development of EVALI, yet it remains unclear whether VEA has direct pulmonary toxicity. To test the hypotheses that aerosolized VEA causes lung injury in mice and directly injures human alveolar epithelial cells, we exposed adult mice and primary human alveolar epithelial type II (AT II) cells to an aerosol of VEA generated by a device designed for vaping oils. Outcome measures in mice included lung edema, BAL analysis, histology, and inflammatory cytokines; in vitro outcomes included cell death, cytokine release, cellular uptake of VEA, and gene-expression analysis. Comparison exposures in both models included the popular nicotine-containing JUUL aerosol. We discovered that VEA caused dose-dependent increases in lung water and BAL protein compared with control and JUUL-exposed mice in association with increased BAL neutrophils, oil-laden macrophages, multinucleated giant cells, and inflammatory cytokines. VEA aerosol was also toxic to AT II cells, causing increased cell death and the release of monocyte and neutrophil chemokines. VEA was directly absorbed by AT II cells, resulting in the differential gene expression of several inflammatory biological pathways. Given the epidemiological and clinical characteristics of the EVALI outbreak, these results suggest that VEA plays an important causal role.

Pediatric Chest Radiographic and CT Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI).

Background Electronic cigarette or vaping product use-associated lung injury (EVALI) is a serious public health concern with substantial morbidity and mortality, particularly in young individuals. Purpose To evaluate chest radiographic and chest CT findings of EVALI in the pediatric population. Materials and Methods This was a retrospective study of children who presented to a tertiary pediatric hospital from December 2018 to December 2019. Patients fulfilled the Centers for Disease Control and Prevention criteria for EVALI and had chest radiographs and CT images available at initial presentation. Two pediatric radiologists independently reviewed imaging for pattern, distribution, and extent of pulmonary abnormalities, as well as for extrapulmonary abnormalities. Clinical information, management, and outcomes were reviewed. Interobserver agreement was measured with Cohen κ coefficient. Results Seven male patients (50%) and seven female patients (50%) (mean age, 16 years; range, 13-18 years) were evaluated. All patients underwent chest radiography and CT within 4 days of presentation (range, 0-4 days). Chest radiographic findings included ground-glass opacity in 14 of 14 (100%) and consolidation in eight of 14 (57%). CT findings included ground-glass opacity in 14 of 14 (100%), consolidation in nine of 14 (64%), and interlobular septal thickening in two of 14 (14%). At CT, subpleural sparing was seen in 11 of 14 (79%) and a reversed halo sign was seen in five of 14 (36%). Chest radiographic and CT abnormalities were predominately bilateral in 14 of 14 (100%) and symmetric in 13 of 14 (93%), with lower lobe predominance in seven of 14 (50%). Extent of abnormality was predominately diffuse at both chest radiography and CT. There was almost perfect interobserver agreement between two reviewers for detecting abnormalities on chest radiographs (κ = 0.99; 95% confidence interval: 0.97, 1.00) and CT (κ = 0.99; 95% confidence interval: 0.98, 1.00). Conclusion In pediatric patients, electronic cigarette or vaping product use-associated lung injury is characterized by bilateral symmetric ground-glass opacities, consolidation, and a lower lobe predominance at CT. © RSNA, 2020.

E-cigarette use related lung disease, review of clinical and imaging findings in 3 cases

Electronic-cigarette use (vaping), has gained popularity among the young adult population, causing an alarming rise in electronic-cigarette, or vaping, product use-associated lung injury (EVALI). The specific chemical agent(s) responsible for lung injuries remains to be further investigated, but tetrahydrocannabinol, the active ingredient in marijuana, and vitamin E acetate are involved in most cases. A variety of pulmonary diseases causing different imaging findings have been described with EVALI. The clinical and imaging findings of three cases recently seen in our emergency department are reviewed.

Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions.

Proposed as a safer alternative to smoking, the use of electronic cigarettes has not proven to be innocuous. With numerous deaths, there is an increasing degree of public interest in understanding the symptoms, imaging appearances, causes of, and treatment of electronic cigarette or vaping product use-associated lung injury (EVALI). Patients with EVALI typically have a nonspecific clinical presentation characterized by a combination of respiratory, gastrointestinal, and constitutional symptoms. EVALI is a diagnosis of exclusion; the patient must elicit a history of recent vaping within 90 days, other etiologies must be eliminated, and chest imaging findings must be abnormal. Chest CT findings in EVALI most commonly show a pattern of acute lung injury on the spectrum of organizing pneumonia and diffuse alveolar damage. The pathologic pattern found depends on when in the evolution of the disease process the biopsy sample is taken. Other less common forms of lung injury, including acute eosinophilic pneumonia and diffuse alveolar hemorrhage, have also been reported. Radiologists and pathologists help play an important role in the evaluation of patients suspected of having EVALI. Accurate and rapid identification may decrease morbidity and mortality by allowing for aggressive clinical management and glucocorticoid administration, which have been shown to decrease the severity of lung injury in some patients. In this review, the authors summarize the current state of the art for the imaging and pathologic findings of this disorder and outline a few of the major questions that remain to be answered.