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A Vaporizing Revelation

Unexplained Hemoptysis
      A 21-year-old man presented to the ED via ambulance for unresponsiveness. The patient’s girlfriend had called emergency medical services to the patient’s home after finding him unconscious. On arrival of emergency medical services, the patient was found to be cyanotic with miosis. Initial peripheral capillary oxygen saturation was 78%. He was placed on 10 L/min of oxygen by nasal cannula and given 1 mg of naloxone intravenously. Emergency medical services reported improvement in mental status with these combined interventions; however, bright red hemoptysis had developed in route. In the ED, further history revealed that the patient had a history of using a vaporizer with a frequency of 1 pod per day. He admitted to inhaled marijuana earlier that day as well but denied using THC-containing vaping products for more than a month. He was asymptomatic the day before symptom onset.
      On physical examination, the patient was afebrile (36.8 ° C ) with a heart rate of 117 beats per minute and a BP of 134/57 mm Hg. He was tachypneic with 28 respirations per minute with increased work of breathing. Lung auscultation revealed coarse breath sounds without overt wheezing. Although the patient initially denied cough, he continued to have hemoptysis in the ED. Initial laboratory values were notable for leukocytosis, elevated lactate, and normal hemoglobin, prothrombin time, and international normalized ratio.
      Despite a nasal cannula and nonrebreather set to 15 L/min of oxygen, the patient remained hypoxic at 91% with increased work of breathing. He was transitioned to heated high-flow nasal cannula with improvement of his oxygen saturation to 98% but continued to exhibit increased work of breathing. Given the patient's worsening respiratory status despite noninvasive interventions, the decision was made, in conjunction with the pulmonology service, to intubate the patient with a plan to perform emergent bronchoscopy. A focused cardiac and lung ultrasound scan were performed at the bedside. The cardiac ultrasound scan was unremarkable, which included a normal ejection fraction. The lung protocol included bilateral anterior and posterolateral zones of the lung. Lung ultrasound images were obtained (Video 1).

       Question

      What is the differential diagnosis for this patient based on clinical history and imaging findings and what is the next step in diagnosis?

       Answer

      Answer: The differential would include electronic vaping associated lung injury (EVALI), ARDS, pulmonary contusion, pneumonia, or cardiogenic pulmonary edema. The next step in diagnosis is chest radiography, CT scanning, or bronchoscopy.
      The POCUS images performed by the emergency physician showed normal lung sliding in anterior lung fields, with bilateral B-lines in the posterolateral lungs without pleural effusion (Fig 1, Narration Video). There were no secondary findings of pneumoma, such as obvious consolidation or dynamic air bronchograms. A chest radiography showed confluent small nodular opacities favored to reflect extensive airspace disease, with a symmetric basilar predominance (Fig 2). Subsequent CT pulmonary angiography of the chest also showed extensive symmetric multifocal airspace disease (Fig 3).
      Figure thumbnail gr1
      Figure 1Point-of-care ultrasound image shows diffuse B-lines bilaterally consistent with interstitial edema. The A, right lung base and B, left lung base are seen cephalad to the diaphragm.
      Figure thumbnail gr2
      Figure 2Anteroposterior radiograph of the chest shows confluent small nodular opacities favored to reflect extensive airspace disease, with a symmetric basilar predominance. L = left.
      Figure thumbnail gr3
      Figure 3CT image of the chest shows extensive symmetric multifocal airspace disease.
      The patient was started on empiric antibiotics for community-acquired pneumonia with ceftriaxone and azithromycin. Methylprednisolone was administered after consultation with pulmonary medicine. On admission to the ICU, the patient underwent bedside bronchoscopy that demonstrated diffuse alveolar hemorrhage. Cultures from BAL washings did not result in subsequent bacterial or fungal growth. Blood cultures likewise showed no growth, and the respiratory viral panel was negative for common viral pathogens. The echocardiogram was read as normal without evidence of systolic or diastolic dysfunction. Autoimmune serology specimens were negative for anti-neutrophil cytoplasmic antibody, anti-myeloperoxidase antibody, anti-proteinase 3 antibody, and anti-glomerular basement membrane antibody. The patient was weaned gradually from the ventilator and extubated on hospital day 3. His work up for cardiac, infectious, and rheumatologic causes was negative, and he subsequently was discharged home. On follow up 14 days after admission and after abstinence from smoking and vaping, the patient underwent repeat CT scanning of his chest that showed complete resolution of previously noted lung changes. He continued to experience dyspnea with significant exertion but was generally asymptomatic and able to perform daily activities without difficulty.

      Discussion

      EVALI is a relatively recently described phenomenon with high morbidity. As of February 18, 2020, the United States’ Centers for Disease Control and Prevention (CDC) has reported a total of 2,807 hospitalized EVALI cases in the United States, including 68 confirmed deaths with an age range of 15 to 75 years. Components found in electronic cigarettes, vaporizers, electronic hookahs, and electronic nicotine delivery systems are listed as potential causative agents.
      Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products
      Centers for Disease Control and Prevention. Accessed March 25, 2020.
      The CDC defines EVALI as a pulmonary infiltrate seen on chest radiography or CT scanning with e-cigarette use within 90 days prior to onset of symptoms. At present, EVALI remains a diagnosis of exclusion because no specific test or marker currently exists for its diagnosis. Respiratory, GI, and constitutional symptoms in combination with a history of recent e-cigarette use should raise clinical suspicion for possible EVALI.
      For Healthcare Providers
      Centers for Disease Control and Prevention. Accessed March 25, 2020.
      Vaping-associated lung injuries have demonstrated a wide range of lung patterns on radiography and CT scanning. Henry et al
      • Henry T.S.
      • Kligerman S.J.
      • Raptis C.A.
      • Mann H.
      • Sechrist J.W.
      • Kanne J.P.
      Imaging findings of vaping-associated lung injury.
      summarized the imaging findings that included hypersensitivity pneumonitis, diffuse alveolar hemorrhage, acute eosinophilic pneumonia, organizing pneumonia, lipoid pneumonia, and giant cell interstitial pneumonia. A case series presented by Kaliniskiy et al
      • Kalininskiy A.
      • Bach C.T.
      • Nacca N.E.
      • et al.
      E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach.
      suggested a diagnostic approach that included radiography and CT scanning for initial evaluation of EVALI. To date, however, there have been no documented cases that included the use of ultrasound scanning as an initial modality for evaluation. Ultrasound scanning continues to be recognized as an essential modality to the provision of high-quality, timely and cost-effective patient care, especially in the emergency setting.
      Beginning with the BLUE protocol described by Lichenstein,
      • Lichtenstein D.A.
      BLUE-protocol and FALLS-protocol: two applications of lung ultrasound in the critically ill.
      many lung ultrasound protocols have been described in the acute care setting. In our case, we evaluated the anterior and posterolateral lungs bilaterally. Additional views were not feasible in the ED, given the patient’s high acuity; however, more views generally increase the sensitivity for pathologic evaluation. At a minimum, a lung protocol should include an evaluation of the least dependent part of the lung (anterior chest in a supine patient) and the most dependent part of the lung (posterior chest in a supine patient) bilaterally. It should be noted that, in this case, a low frequency curvilinear transducer was used primarily, which allowed for a broad field of view over multiple rib spaces. Tissue harmonic imaging and other artifact-reducing technologies should be turned off to allow for best visualization of the pathologic lung artifacts. A high-frequency linear probe can be useful for further characterizing the pleural line. In this case, detailed evaluation of the pleural line was limited because of the use of a low-frequency probe. From what could be observed, the pleural line was regular and continuous without overt subpleural consolidations. It has been suggested that pleural abnormalities are more indicative of an inflammatory or infectious cause of pulmonary edema as opposed to cardiogenic pulmonary edema, but these findings were not readily apparent in our case.
      • Copetti R.
      • Soldati G.
      • Copetti P.
      Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome.
      Patchy B-lines, with spared areas of the lung also, would challenge the possibility of a cardiogenic cause. The patient had few B-lines in the anterior right lung field, whereas there were diffuse B-lines in the bilateral bases of the lungs. It is unclear whether this was indicative of basilar predominance of the edema or a patchiness of the lung ultrasound findings. The bedside cardiac ultrasound scan showed a preserved left ventricular ejection fraction and collapsible inferior vena cava that supports a noncardiogenic cause. These sonographic lung findings together suggest a systemic inflammatory process to be causing increased interstitial edema. This is corroborated by the findings on chest CT scanning. In a patient with vaping-associated diffuse alveolar hemorrhage, these sonographic findings would be expected, based on what has been seen on other imaging modalities.
      • Agustin M.
      • Yamamoto M.
      • Cabrera F.
      • Eusebio R.
      Diffuse alveolar hemorrhage induced by vaping.
      ,
      • Edmonds P.J.
      • Copeland C.
      • Conger A.
      • Richmond B.W.
      Vaping-induced diffuse alveolar hemorrhage.
      In previous case reports and case series, chest radiography and CT scanning have been the initial imaging modalities of choice.
      • Kalininskiy A.
      • Bach C.T.
      • Nacca N.E.
      • et al.
      E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach.
      ,
      • Edmonds P.J.
      • Copeland C.
      • Conger A.
      • Richmond B.W.
      Vaping-induced diffuse alveolar hemorrhage.
      This is consistent with the aforementioned diagnostic criteria set by the CDC. We present a case of EVALI during which point-of-care ultrasound scanning (POCUS) was used during initial resuscitation and diagnostic workup in the ED setting. The sonographic features of this case of EVALI included bilateral B-lines representative of interstitial edema. B-lines are a reverberation artifact that originate from the pleural line caused by a thickening of the interstitium; these findings have been described with other pathologic findings that include cardiogenic pulmonary edema, pulmonary contusion, pneumonia, and ARDS.
      • Lichtenstein D.A.
      BLUE-protocol and FALLS-protocol: two applications of lung ultrasound in the critically ill.
      ,
      • Copetti R.
      • Soldati G.
      • Copetti P.
      Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome.
      ,
      • Hosseini M.
      • Ghelichkhani P.
      • Baikpour M.
      • et al.
      Diagnostic accuracy of ultrasonography and radiography in detection of pulmonary contusion; a systematic review and meta-analysis.
      Because this is the first description of lung ultrasound scanning in a patient with EVALI, there are no established guidelines regarding how ultrasound scanning can assist in the diagnostic work up. Given the nonspecific nature of the sonographic findings, we propose that POCUS can be used to increase suspicion for the disease process in a patient with a high pretest probability for EVALI based on history and examination. POCUS has the advantage of being able to be performed rapidly at the bedside of a critically ill patient whose condition may be too unstable to move for CT scanning. In addition, POCUS can be more sensitive for interstitial edema than chest radiography.
      • Danish M.
      • Agarwal A.
      • Goyal P.
      • et al.
      Diagnostic performance of 6-point lung ultrasound in ICU patients: a comparison with chest x-ray and CT thorax.
      Furthermore, POCUS of the heart and lungs effectively can rule out alternate diagnoses such as pneumothorax, pneumonia, pleural effusion, pericardial effusion, and acute heart failure. Therefore, POCUS can be used early in the course of a patient with suspected EVALI to expedite treatment; however, the diagnosis should be confirmed with further diagnostic testing, given that the sonographic findings are not specific.

      Reverberations

      • 1.
        The sonographic lung findings of EVALI are a regular pleural line and bilateral B-lines with basilar predominance reflective of interstitial edema.
      • 2.
        POCUS can be used to increase suspicion for EVALI in a patient with high pretest probability and to evaluate for alternate causes of acute dyspnea.
      • 3.
        POCUS in isolation should not be used to diagnose EVALI. Due to the nonspecific nature of the findings on lung sonography, the diagnosis should be confirmed with additional diagnostic testing.

      Acknowledgments

      Financial/nonfinancial disclosures: None declared.
      Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
      Additional information: To analyze this case with the Videos, see the online version of this article.

      Supplementary Data

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