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• W3009987924 abstract "The use of e-cigarettes to deliver aerosolized nicotine has gained popularity in recent years. Numerous reports have cited the development of acute pulmonary disease linked to vaping nicotine as well as marijuana-based products. As cultural attitudes evolve and policies shift toward the legalization of marijuana, its use has become more prevalent. Given the increased prevalence of marijuana consumption and e-cigarette usage, better insight into its potential to cause lung toxicity is warranted. The clinical, radiographic, and histopathologic characteristics of lung injury associated with vaping, particularly with marijuana-based products, have yet to be well described in the literature. We present eight patients, most of whom were admitted recently to our institution with acute respiratory failure following vaping. The majority of patients were young, with a median age of 31.5 years (range, 24-62 years) and with no known underlying lung disease. This case series highlights common clinical findings as well as the varied radiographic and histopathologic features of acute respiratory failure associated with vaping predominantly marijuana-based products. As more cases of vaping-associated pulmonary injury unfold, data will be available to further characterize this emerging disease entity. Improved understanding of disease pathogenesis and its clinical course will help clinicians determine optimal management and follow-up strategies for this patient population. The use of e-cigarettes to deliver aerosolized nicotine has gained popularity in recent years. Numerous reports have cited the development of acute pulmonary disease linked to vaping nicotine as well as marijuana-based products. As cultural attitudes evolve and policies shift toward the legalization of marijuana, its use has become more prevalent. Given the increased prevalence of marijuana consumption and e-cigarette usage, better insight into its potential to cause lung toxicity is warranted. The clinical, radiographic, and histopathologic characteristics of lung injury associated with vaping, particularly with marijuana-based products, have yet to be well described in the literature. We present eight patients, most of whom were admitted recently to our institution with acute respiratory failure following vaping. The majority of patients were young, with a median age of 31.5 years (range, 24-62 years) and with no known underlying lung disease. This case series highlights common clinical findings as well as the varied radiographic and histopathologic features of acute respiratory failure associated with vaping predominantly marijuana-based products. As more cases of vaping-associated pulmonary injury unfold, data will be available to further characterize this emerging disease entity. Improved understanding of disease pathogenesis and its clinical course will help clinicians determine optimal management and follow-up strategies for this patient population. The use of e-cigarettes to deliver aerosolized nicotine has gained popularity.1Miech R. Patrick M.E. O'Malley P.M. Johnston L.D. What are kids vaping? Results from a national survey of US adolescents.Tob Control. 2017; 26: 386-391Crossref PubMed Scopus (95) Google Scholar,2Budney A.J. Sargent J.D. Lee D.C. Vaping cannabis (marijuana): parallel concerns to e-cigs?.Addiction. 2015; 110: 1699-1704Crossref PubMed Scopus (130) Google Scholar e-Cigarettes were initially developed as a safer and more socially acceptable alternative for tobacco consumption compared with combustion cigarettes. However, in vitro experiments have shown that e-cigarettes can induce lung injury,3Ghosh A. Coakley R.C. Mascenik T. et al.Chronic E-cigarette exposure alters the human bronchial epithelial proteome.Am J Respir Crit Care Med. 2018; 198: 67-76Crossref PubMed Scopus (140) Google Scholar characterized by epithelial cell and fibroblast cytotoxicity, decreased cell viability, and cytokine release.4Rowell T.R. Tarran R. Will chronic e-cigarette use cause lung disease?.Am J Physiol Lung Cell Mol Physiol. 2015; 309: L1398-L1409Crossref PubMed Scopus (83) Google Scholar Injury and gas exchange disturbances may occur with or without the presence of nicotine, implicating the adverse role of additive chemicals such as propylene glycol, glycerol, illicit drugs, and various flavorings.5Chaumont M. van de Borne P. Bernard A. et al.Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchange disturbances: results from two randomized clinical trials.Am J Physiol Lung Cell Mol Physiol. 2019; 316: L705-L719Crossref PubMed Scopus (75) Google Scholar,6Chaumont M. Bernard A. Pochet S. et al.High-wattage E-cigarettes induce tissue hypoxia and lower airway injury: a randomized clinical trial.Am J Respir Crit Care Med. 2018; 198: 123-126Crossref PubMed Scopus (20) Google Scholar Clinically, e-cigarette use has been associated with the development of interstitial lung disease,7Flower M. Nandakumar L. Singh M. Wyld D. Windsor M. Fielding D. Respiratory bronchiolitis-associated interstitial lung disease secondary to electronic nicotine delivery system use confirmed with open lung biopsy.Respirol Case Rep. 2017; 5e00230Crossref PubMed Scopus (46) Google Scholar lipoid pneumonia,8Viswam D. Trotter S. Burge P.S. Walters G.I. Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes.BMJ Case Rep. 2018; 2018PubMed Google Scholar eosinophilic pneumonia,9Thota D. Latham E. Case report of electronic cigarettes possibly associated with eosinophilic pneumonitis in a previously healthy active-duty sailor.J Emerg Med. 2014; 47: 15-17Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar tension pneumothorax,10Lo T. Vaping and tension pneumothorax: a life-threatening association.Am J Respir Crit Care Med. 2017; 195PubMed Google Scholar diffuse alveolar hemorrhage,11Agustin M. Yamamoto M. Cabrera F. Eusebio R. Diffuse alveolar hemorrhage induced by vaping.Case Rep Pulmonol. 2018; 2018: 9724530Crossref PubMed Google Scholar and asthma exacerbation.12Bradford L.E. Rebuli M.E. Ring B.J. Jaspers I. Clement K.C. Loughlin C.E. Danger in the vapor? ECMO for adolescents with status asthmaticus after vaping.J Asthma. 2019; : 1-5Crossref Scopus (29) Google Scholar Although the use of e-cigarettes to consume nicotine is common, e-cigarettes can also be used with nicotine-free products, including marijuana.13Trivers K.F. Phillips E. Gentzke A.S. Tynan M.A. Neff L.J. Prevalence of cannabis use in electronic cigarettes among US youth.JAMA Pediatr. 2018; 172: 1097-1099Crossref PubMed Scopus (68) Google Scholar A popular means of marijuana usage is to heat the product (liquid, oil, or plant-based material) to a specific temperature that releases the aerosolized active ingredient, tetrahydrocannabinol (THC), which is then inhaled.2Budney A.J. Sargent J.D. Lee D.C. Vaping cannabis (marijuana): parallel concerns to e-cigs?.Addiction. 2015; 110: 1699-1704Crossref PubMed Scopus (130) Google Scholar Numerous reports have cited the development of acute pulmonary disease linked to e-cigarettes and other vaping products.14Kaplan S. Dozens of young people hospitalized for breathing and lung problems after vaping. The New York Times. 2019 [cited 2019 Aug 18];A20.https://www.nytimes.com/2019/08/14/health/vaping-marijuana-e-cigarettes.html. Accessed August 18, 2019.Google Scholar,15Pneumotox II (V2.2-mobile) App. Producer: Ph Camus Dijon France. https://urldefense.proofpoint.com/v2/url?u=https-3A__www.pneumotox.com&d=DwIFaQ&c=vq5m7Kktb9l80A_wDJ5D-g&r=okhwsugdSnXB8Buu4j9Cv6b6IEOdNFZ_4z4XPXUp2ps&m=TZzwJsiCWywtVdL4IdYvvck2KHSpyTySEcbLasqE_qw&s=ExRhqIro5ltiOTYgrxC7wBLwqpuAwccC8CQWeAnD9gk&e=. Accessed September 15, 2019.Google Scholar Recently, the New York State Department of Health issued an advisory on vaping-associated pulmonary illness.16New York State Department of Health Issues Health Advisory on Vaping-Associated Pulmonary Illness [press release]. https://www.health.ny.gov/press/releases/2019/2019-08-16_health_advisory.htm. Accessed August 16, 2019.Google Scholar Better insight into the potential of e-cigarettes to cause lung toxicity is warranted. To the best of our knowledge, the clinical, radiographic, and histopathologic characteristics of lung injury associated with vaping, particularly with marijuana-containing products, have yet to be described. We present eight patients, all but one who presented between November 2018 and August 2019, with acute respiratory failure (ARF) following vaping. Seven of the eight cases had no history of underlying lung disease. All tested negative for HIV, antineutrophil cytoplasmic antibodies, and antinuclear antibody. Infectious evaluation for each patient included a rapid viral panel, blood cultures, and legionella antigen. All patients were counseled on vaping cessation and the potential dangers of e-cigarettes. A 29-year-old man presented with 9 days of productive cough, dyspnea, and fever. He vaped nicotine daily and THC oil weekly, confirmed by positive urine toxicology results. He was hypoxemic on room air (Pao2, 40 mm Hg; Paco2, 41 mm Hg). He had an elevated C-reactive protein (CRP) level (366.1 mg/L) and erythrocyte sedimentation rate (ESR) (91 mm/h). Results of rheumatologic and infectious evaluations were negative except for rhinovirus on viral panel. Chest CT imaging revealed reticular and ground-glass opacities (GGO) in the lower lobes with a peribronchovascular distribution and subpleural sparing (Fig 1). BAL revealed predominantly macrophages and neutrophils, and was negative for infectious organisms. Transbronchial lung biopsy (TBLB) results showed acute inflammation, type 2 pneumocyte hyperplasia, and focal intra-alveolar fibrin (Fig 2). The patient was administered broad-spectrum antibiotics and methylprednisolone 1 mg/kg intravenously followed by a prednisone taper. He symptomatically improved over an 8-day course and was discharged on a steroid taper. At a 2-week outpatient follow-up, the patient’s ESR and CRP levels had normalized.Figure 2Case 1: Acute inflammation (red arrow), type 2 pneumocyte hyperplasia (blue arrow), and focal intra-alveolar fibrin (black arrow) (hematoxylin-eosin, 200×).View Large Image Figure ViewerDownload Hi-res image Download (PPT) A 34-year-old man presented with 5 days of nonproductive cough, dyspnea, and malaise. He had vaped marijuana for several years. He was febrile and hypoxemic, saturating 94% on room air. He had an elevated CRP (195.8 mg/L). Results of hematologic and infectious evaluations were negative. A chest CT scan revealed GGO with an upper lobe distribution and dense lower lobe consolidations. The patient received empiric antibiotics; steroids were not administered. He symptomatically improved over 1 week and was discharged home. A 24-year-old woman presented with 1 week of nonproductive cough, dyspnea, malaise, and headache. She vaped THC oil daily. She was febrile and hypoxemic, saturating 94% on room air. Her levels of CRP (234.7 mg/L) and ESR (106 mm/h) were elevated. Results of an infectious evaluation, including BAL, were negative, and rheumatoid factor was elevated (16 IU/mL). Chest CT imaging showed GGO with upper lobe distribution and lower lobe dense consolidations with subpleural sparing. The patient underwent video-assisted thoracoscopic surgery biopsy, which revealed diffuse alveolar damage, intra-alveolar hemorrhage with focal acute capillaritis, type 2 pneumocyte hyperplasia, and organizing pneumonia (Fig 3). BAL was negative for infectious organisms. The patient received empiric antibiotics and methylprednisolone 1 mg/kg intravenously daily followed by one dose of rituximab. The patient clinically improved over 19 days and was discharged home with a prednisone taper. At her 3-week follow-up, the patient noted improvement in respiratory symptoms but not to baseline. A 54-year-old man presented with 3 days of productive cough, dyspnea, and submassive hemoptysis. He vaped marijuana twice weekly. He was febrile and hypoxemic, saturating 90% on room air. Results of rheumatologic and infectious evaluations were negative, and results of laboratory tests were notable for elevated CRP (243.8 mg/L) and ESR (66 mm/h). Chest CT imaging showed bilateral diffuse nodular opacities with centrilobular distribution. BAL revealed diffuse alveolar hemorrhage with neutrophil predominance and was negative for infectious organisms. TBLB results revealed organizing pneumonia, type 2 pneumocyte hyperplasia, and focal intra-alveolar fibroblastic proliferation (Fig 4). The patient received empiric antibiotics; no steroids were administered. He clinically improved over 4 days and was then discharged home. Symptoms and imaging had resolved at the 1-month follow-up. A 27-year-old woman presented with 1 week of productive cough, dyspnea, and headache. She had vaped THC oil every other day for 2 months. She was febrile and hypoxemic, saturating 92% on room air. Results of rheumatologic and infectious evaluations were negative, and results of laboratory tests were notable for elevated levels of CRP (35.5 mg/L) and ESR (120 mm/h). Chest CT imaging showed patchy, bilateral GGO. She received empiric antibiotics followed by methylprednisolone 1 mg/kg intravenously daily, which was quickly tapered. BAL was neutrophil-predominant and negative for infectious organisms. The patient clinically improved over 8 days and was discharged on a prednisone taper. Her symptoms had resolved at the 10-day follow-up, and ESR and CRP had improved as well. A 25-year-old man presented with 3 weeks of productive cough and dyspnea. He vaped marijuana several times per week, confirmed by urine toxicology reports. He was febrile and hypoxemic (Pao2, 40 mm Hg; Paco2, 40 mm Hg). Results of rheumatologic and infectious evaluations were negative, and results of laboratory tests were notable for elevated levels of CRP (31.8 mg/L) and ESR (63 mm/h). Chest CT imaging showed diffuse and bilateral GGO with a peribronchovascular distribution and subpleural sparing (Fig 5). BAL was neutrophil-predominant and negative for infectious organisms. TBLB results showed organizing pneumonia, intra-alveolar fibrin, and type 2 pneumocyte hyperplasia. The patient was administered empiric antibiotics and methylprednisolone 1 mg/kg intravenously daily. He improved over the course of 11 days and was discharged home with a prednisone taper. A 62-year-old woman with history of mild intermittent asthma presented with 1 month of dyspnea and abdominal pain. She had received antibiotics prior to presentation. She had vaped nicotine-based products for 6 months. She was afebrile and normoxemic at the time of presentation. Results of rheumatologic and infectious evaluations were negative; chest CT imaging showed bilateral, diffuse, patchy, and nodular consolidations with a peribronchovascular distribution. BAL cell differential was 21% eosinophils, 27% neutrophils, and 36% lymphocytes, and was negative for infectious organisms. Modest peripheral eosinophilia was present on admission (0.59 K/μL [12%]). TBLB results showed organizing pneumonia, mild chronic inflammation, and type 2 pneumocyte hyperplasia. The patient was treated with empiric antibiotics. She clinically improved over 5 days without steroids and was discharged home. A 35-year-old man presented with 4 days of nonproductive cough, dyspnea, malaise, and headache. He vaped marijuana weekly, confirmed by urine toxicology reports. He was hypoxemic (Pao2, 46 mm Hg; Paco2, 39 mm Hg) and febrile. Results of rheumatologic and infectious evaluations were negative. Laboratory test results were notable for elevated CRP (30.1 mg/L) and ESR (105 mm/h). Chest CT imaging showed diffuse, bilateral GGO and consolidations with subpleural sparing. Bronchoscopy was deferred. He received empiric antibiotics; steroids were not started. The patient clinically improved over 6 days and was discharged home. To our knowledge, this case series is the first to report ARF associated with the use of e-cigarettes. Seven of eight cases were related to vaping marijuana, one of which was in combination with nicotine. Most patients were young and without underlying lung disease (Table 1). Dyspnea and cough were predominant symptoms. Fever occurred in all who vaped marijuana and/or marijuana oil and, for some, persisted for weeks following discontinuation. Systemic inflammatory response was pronounced with elevated ESR and CRP levels. Results of rheumatologic and infectious evaluations were negative for all patients, except in one who had an indeterminate rheumatoid factor and another with rhinovirus. There was a spectrum of radiographic features. Common features included GGO, primarily in the upper lobes, and areas of consolidation with lower lobe predominance. One pattern was noted to be centrilobular, with tree-in-bud. One-half of the cases showed subpleural sparing on CT imaging (Table 2). These cases did not show evidence of hypersensitivity pneumonitis, lipoid pneumonia, or eosinophilic pneumonia on pathology. One patient with asthma had peripheral eosinophilia and BAL with 21%eosinophils but did not have eosinophilic pneumonia on pathology. Six of eight patients underwent bronchoscopy. Histopathologic characteristics included organizing pneumonia in four of six cases and in one case, diffuse alveolar damage and capillaritis. All patients received empiric antibiotics, one-half received steroids, and one received a single dose of rituximab due to suspicion for vasculitis, which was discontinued following a negative rheumatologic evaluation. All patients symptomatically improved within a short amount of time following cessation of vaping. Median time to discharge was 7.5 days (range, 4-19 days). One patient had follow-up imaging with complete resolution at 2 weeks. All patients reported improvement in respiratory symptoms. Long-term follow-up data are not yet available. This case series highlights common clinical features as well as radiographic and histopathologic findings of ARF associated with vaping predominantly marijuana-based products. Although these products could not be assessed for species subtype or potency, the lung injury pattern is characterized by a marked inflammatory response. The pathophysiological mechanism remains unclear. The presence of subpleural sparing suggests inhalational injury. Alternative mechanisms may include direct thermal injury from high wattage e-cigarettes and chemical injury from additive agents such as propylene glycol and glycerol.6Chaumont M. Bernard A. Pochet S. et al.High-wattage E-cigarettes induce tissue hypoxia and lower airway injury: a randomized clinical trial.Am J Respir Crit Care Med. 2018; 198: 123-126Crossref PubMed Scopus (20) Google Scholar Further investigation is warranted regarding the respective merit of cessation of exposure and steroid use. Moreover, the diagnostic roles of bronchoscopy and biopsy have yet to be established. This case series illustrates that vaping contributes to lung injury in otherwise healthy individuals and must be considered in patients who present with acute respiratory illness and endorse vaping.Table 1Patient DataCase No.Age (y)SexUnderlying Lung DiseaseVaping SubstanceDurationFrequency129MaleNoMarijuana + nicotineUnknownMarijuana weeklyNicotine daily234MaleNoMarijuanaSeveral yearsUnknown324FemaleNoMarijuanaUnknownDaily454MaleNoMarijuanaUnknownTwice weekly527FemaleNoMarijuana2 monthsEvery other day625MaleNoMarijuanaUnknownSeveral times per week762FemaleAsthmaNicotine6 monthsUnknown835MaleNoMarijuanaUnknownWeekly Open table in a new tab Table 2Radiographic FindingsCase No.Dominant PatternDistributionSubpleural SparingAdditional Characteristics1ReticularGround-glassLower lobeBilateralYesPeribronchovascular distribution2Ground-glassConsolidationDiffuseBilateralNoGround-glass predominates in upper lobesConsolidation predominates in lower lobe3Ground-glassConsolidationLower lobeBilateralYesGround-glass predominates in upper lobesConsolidation predominates in lower lobes4NodularConsolidationDiffuseBilateralNoCentrilobular nodules5Ground-glassDiffuseBilateralNoPatchy distribution6Ground-glassDiffuseBilateralYesPeribronchovascular distribution7NodularConsolidationDiffuseBilateralNoPeribronchovascular distribution8Ground-glassConsolidationDiffuseBilateralYes… Open table in a new tab Financial/nonfinancial disclosures: None declared. Other contributions: The authors thank Michael Esposito, MD, for his assistance and providing pathology slides for the manuscript." @default.
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• W3009987924 title "Acute Respiratory Failure Associated With Vaping" @default.
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