Hypersensitivity Pneumonitis andCasey G. Sommerfeld, Acute MD, Daniel Respiratory J. Weiner, MD, Andrew Nowalk, MD, PhD, Distress Allyson Larkin, MD

Syndrome“ From” E-Cigaretteabstract Use Electronic cigarette (e-cigarette) use, or vaping,​ is gaining widespread popularity as an alternative to conventional cigarettes among adolescents. Little is known of the health risks of e-cigarette use, especially in children and adolescents. We present a Case Report of a previously healthy 18-year- old woman who presented with dyspnea, cough, and pleuritic chest pain Department of Pediatrics, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, after e-cigarette use. She developed respiratory failure with hypoxia and Pennsylvania was intubated, and ultimately met diagnostic criteria for acute respiratory Dr Sommerfeld cared for the patient as a resident distress syndrome. Chest tubes were placed to drain worsening pleural on the Infectious Disease service, drafted the effusions. Computed tomography of the chest revealed dependent opacities initial manuscript, and critically reviewed the in both lung bases, superimposed smooth interlobular septal thickening, manuscript; Dr Nowalk was the Infectious Disease attending who was consulted on this patient, and he and pleural effusions. Bronchoalveolar lavage revealed cellular debris assisted in the interpretation of data, contributed and reactive mononuclear cells, and cell counts were remarkable for his expertise toward the patient’s care, and elevated mononuclear cells and eosinophilia. After the results of a workup critically reviewed and revised the manuscript for important intellectual content; Dr Weiner was the for an infectious etiology came back negative, the patient was diagnosed Pulmonology attending who was consulted on this with hypersensitivity pneumonitis and intravenous methylprednisolone patient, and he assisted in the interpretation of therapy was initiated. After this the patient rapidly improved, was weaned data, contributed his expertise toward the patient’s off vasopressor support, and was extubated. This is the first reported care, and critically reviewed and revised the manuscript for important intellectual content; case of hypersensitivity pneumonitis and acute respiratory distress Dr Larkin was the Allergy and Immunology attending syndrome as a risk of e-cigarette use in an adolescent, and it should prompt who was consulted on this patient, and she assisted pediatricians to discuss the potential harms of vaping with their patients. in the interpretation of data, contributed her expertise toward the patient’s care, and critically Hypersensitivity pneumonitis, lipid pneumonia, and eosinophilic pneumonia reviewed and revised the manuscript for important should be included in the differential diagnosis of patients who exhibit intellectual content; and all authors approved the respiratory symptoms after the use of an e-cigarette. final manuscript as submitted and agree to be accountable for all aspects of the work. DOI: https://​doi.​org/​10.​1542/​peds.​2016-​3927 Tobacco use remains a significant reports researchers have documented Accepted for publication Jun 28, 2017 public health issue in pediatric respiratory consequences mostly in Address correspondence to Casey G. Sommerfeld, “ ” patients. The use of electronic the adult population. The youngest MD, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave, AOB Suite 5400, cigarettes (e-cigarettes), or vaping,​ patient so far described is a 20-year- Pittsburgh, PA 15224. E-mail: Casey.Sommerfeld@ is gaining widespread popularity as an old man diagnosed with acute choa.org alternative to conventional cigarettes. eosinophilic pneumonitis immediately PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, Recent data from the National Youth after smoking an e-cigarette. Although 1098-4275). Tobacco survey revealed a threefold he presented with respiratory Copyright © 2018 by the American Academy of increase in e-cigarette use between the symptoms, his oxygen saturations Pediatrics years 2011 and 2013 in adolescents remained at 100% on room air without a1 previous history of and he did not require respiratory2 To cite: Sommerfeld CG, Weiner DJ, Nowalk A, smoking. support during his admission. In et al. Hypersensitivity Pneumonitis and Acute another report of a 60-year-old man Respiratory Distress Syndrome From E-Cigarette Currently there are limited data on with a presumptive diagnosis of Use. Pediatrics. 2018;141(6):e20163927 the health risks of e-cigarettes in acute hypersensitivity pneumonitis, pediatric patients because in previous this disorder is connected to the Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 141, number 6, June 2018:e20163927 CASE REPORT use of e-cigarettes. This patient Her lung examination was notable The results of a respiratory viral required oxygen supplementation for use of accessory muscles and panel were negative. Bronchoalveolar for hypoxemia but, again,3 no further diminished but clear breath sounds lavage (BAL) revealed cellular debris respiratory support. In 2 further bilaterally at the bases. There was and reactive mononuclear cells. BAL reports, researchers describe lipid no hepatosplenomegaly or digital cell counts were notable for a 900 pneumonia secondary to e-cigarette clubbing. red blood cell count and a 340 white use, and 1 patient required blood cell count (differential of 26% An initial complete blood cell count intubation for acute respiratory × neutrophils, 13% lymphocytes, 14% 4,5​ revealed an elevated white blood distress syndrome. ‍ There are no 3 monocytes, 25% mononuclear cells, cell count of 35.9 ( 10 /mL), with Mycoplasma case reports in the literature in which and 22% eosinophils). The results 93% neutrophils, 4% bands, 1% Legionella researchers describe respiratory of BAL testing for lymphocytes, and 2% monocytes. failure secondary to hypersensitivity polymerase chain reaction, Her hemoglobin level was 13.5 gm/dL, pneumonitis as a consequence of direct fluorescent antibody, and with a platelet count of 309000/mL. e-cigarette use in the pediatric aerobic and fungal cultures were Erythrocyte sedimentation rate Pneumocystis population. all negative. BAL cytology revealed was normal, with an elevated CASE REPORT no but abundant C-reactive protein level of 17.4 mg/L. lipid-laden macrophages on an Electrolytes and transaminases Oil Red O stain. The patient was were normal. Urinalysis and started on 40 mg of intravenous An 18-year-old woman presented urine drug screen results were methylprednisolone twice daily. After to the emergency department both negative. A chest radiograph steroid initiation, she was quickly with a chief complaint of 2 days of revealed patchy bilateral pulmonary weaned from vasopressor support progressive dyspnea, cough, and infiltrates. Computed tomography and was extubated 5 days after initial pleuritic chest pain. She was afebrile (CT) angiography of the chest was presentation. She was eventually during this time and without any negative for pulmonary emboli discharged from the hospital on a upper respiratory symptoms. Her but did reveal dependent opacities prednisone taper with a diagnosis of past medical history was significant in both lung bases, superimposed hypersensitivity pneumonitis, likely for mild intermittent exertional smooth interlobular septal thickening secondary to e-cigarette exposure. asthma, with only rare use of inhaled in the dependent areas of the lungs, albuterol. Recently the patient had and bilateral, small-to-moderate DISCUSSION a reaction (hives and lip swelling) pleural effusions. Brain natriuretic to a Brazil nut that resolved with peptide and cortisol levels were both diphenhydramine. She had not been normal. An echocardiogram revealed Hypersensitivity pneumonitis is an evaluated for nut allergies, but she normal left ventricle systolic function inflammatory disease of the lung had tolerated other nuts without with no valvular dysfunction. parenchyma that is the result of reaction. an immune response to inhaled The patient was admitted to the The patient lived in a rural town and antigens. Typically, hypersensitivity PICU and started on broad-spectrum had no recent bird or farm animal pneumonitis is associated with antibiotics. Her respiratory distress ’ exposure. She had no recent travel, antigens from microbial agents, such rapidly worsened, and she was reverse travel, or close contact with as moldy hay or grains (farmer s intubated for respiratory failure. ’ incarcerated individuals. The patient lung), or with animal proteins in She met diagnostic criteria for acute recently started to use e-cigarettes avian droppings (bird fancier s lung). respiratory distress syndrome, over the last 2 to 3 weeks and had In the acute setting, hypersensitivity requiring a >90% fraction of been using them 1 to 2 days before ∼ o pneumonitis can be secondary to inspired oxygen with a Pa 2 of the onset of symptoms. She was chemical exposure, some of which 70 mmHg. She was ventilated 6 employed as a hostess in a local can be found in e-cigarettes. with a peak inspiratory pressure of restaurant. ’ up to 36 cmH2O and positive end- Hypersensitivity pneumonitis can be On presentation, the patient s vital expiratory pressure of 12 cmH2O. categorized by the duration of illness ° signs were as follows: temperature Norepinephrine therapy was as an acute, subacute, or chronic of 36.8 C, heart rate of 130 beats initiated for poor perfusion, and process. The typical manifestations per minute, respiratory rate of 32 bilateral chest tubes were placed of acute or subacute hypersensitivity breaths per minute, and oxygen for worsening pleural effusions. pneumonitis can mimic a viral saturation of 84% on room air. Her Bronchoscopy revealed normal illness, with symptoms including cardiac examination did not reveal mucosa of the trachea and mainstem fever, cough, dyspnea, myalgias, and any rubs, gallops, or murmurs. bronchi, with clear frothy secretions. arthralgias. In an acute presentation, Downloaded from www.aappublications.org/news by guest on September 26, 2021 2 SOMMERFELD et al symptoms will often begin hours reveal lymphocytosis. Neutrophil agents. In more severely ill patients, after antigen exposure. In a subacute predominance can also be seen in intravenous corticosteroids have or chronic presentation, the either the acute phase with recent been shown9,12​ to accelerate lung symptoms tend to be prolonged and exposures or with more advanced recovery. ‍ Because this is an less severe. With repetitive antigen disease. Increased eosinophil inflammatory response, antibiotics exposure, patients may develop a numbers8 can also be seen in BAL are not useful unless bacterial progressive chronic respiratory samples. superinfection is suspected. disease secondary to pulmonary CONCLUSIONS fibrosis. BAL eosinophilia is also present in acute eosinophilic pneumonia, The diagnosis of hypersensitivity which may present similarly to With this case, we highlight pneumonitis is made by a hypersensitivity pneumonitis. combination of laboratory studies, hypersensitivity pneumonitis as a life- Typical symptoms include fever, threatening health risk of e-cigarette imaging, BAL, and histologic findings. nonproductive cough, dyspnea, If possible, serum immunoglobulin G 9 use in an adolescent patient. Although myalgias, and malaise. A majority little is known of e-cigarette health antibodies to specific antigens should of patients do not have peripheral be obtained. A positive serology risks, especially in children and blood eosinophilia at the time of adolescents, their use in the pediatric result is suggestive but not diagnostic presentation. A complete blood of hypersensitivity pneumonitis, and population is growing rapidly. cell count differential reveals a This should prompt pediatricians the absence of specific antibodies neutrophilic leukocytosis early in (especially in acute presentations) to discuss the potential harms of the course, followed by an eosinophil e-cigarette use with their patients. does not rule out this condition. predominance with disease 10 Hypersensitivity pneumonitis, Chest CT in the acute and subacute progression. Chest CT will reveal setting may reveal nodular, ground lipid pneumonia, and eosinophilic patchy ground glass opacities, usually pneumonia should be included in the glass, or airspace opacities. There located along bronchovascular 11 differential diagnosis of patients who may be small nodules present,7 bundles. The diagnosis of acute which represent granulomas. exhibit respiratory symptoms after eosinophilic pneumonia can be made the use of e-cigarettes. The use of pulmonary function on the basis of clinical features, CT tests can be used to support the findings, and a BAL sample with ABBREVIATIONS diagnosis of hypersensitivity >25% eosinophilia. pneumonitis, typically revealing a reduced diffusing capacity of the The treatment of both BAL: bronchoalveolar lavage lung for carbon monoxide. BAL fluid hypersensitivity pneumonitis and CT: computed tomography is helpful in diagnosis, in which acute eosinophilic pneumonia is e-cigarette: electronic cigarette the leukocyte differential may centered on avoidance of inciting FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 141, number 6, June 2018 3 pneumonitis-​extrinsic-​allergic-​ 10. Allen JN, Pacht ER, Gadek JE, Davis thin-section CT findings in 29 patients. alveolitis. Accessed February 2, 2017 WB. Acute eosinophilic pneumonia as Eur J Radiol. 2008;65(3):462–467 9. Rhee CK, Min KH, Yim NY, et al. a reversible cause of noninfectious 12. Kokkarinen JI, Tukiainen HO, Terho EO. Clinical characteristics and respiratory failure. N Engl J Med. Effect of corticosteroid treatment on corticosteroid treatment of acute 1989;321(9):569–574 the recovery of pulmonary function eosinophilic pneumonia. Eur Respir J. 11. Daimon T, Johkoh T, Sumikawa H, in farmer’s lung. Am Rev Respir Dis. 2013;41(2):402–409 et al. Acute eosinophilic pneumonia: 1992;145(1):3–5

Downloaded from www.aappublications.org/news by guest on September 26, 2021 4 SOMMERFELD et al Hypersensitivity Pneumonitis and Acute Respiratory Distress Syndrome From E-Cigarette Use Casey G. Sommerfeld, Daniel J. Weiner, Andrew Nowalk and Allyson Larkin Pediatrics originally published online May 17, 2018;

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Downloaded from www.aappublications.org/news by guest on September 26, 2021 Hypersensitivity Pneumonitis and Acute Respiratory Distress Syndrome From E-Cigarette Use Casey G. Sommerfeld, Daniel J. Weiner, Andrew Nowalk and Allyson Larkin Pediatrics originally published online May 17, 2018;

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