Vaping-Associated Pulmonary Injury

Etiology

Although the etiology remains unclear, several causes are under investigation. Of these, vitamin E acetate is the most recognized agent associated with an e-cigarette or vaping product use-associated lung injury (EVALI). Supporting this is that a recent study identified vitamin E acetate in bronchoalveolar lavage (BAL) fluid samples of 48 out of the 51 patients with EVALI as opposed to none in the liquid samples obtained from the healthy control group.[2] Vitamin E acetate was illegally used as a diluent in multiple counterfeit, low-cost tetrahydrocannabinol (THC) containing cartridges. Its use as a diluent in THC-based cartridges became common in 2019, coinciding with the EVALI outbreak.[3] However, the possibility of other agents, including chemicals in either THC or non-THC products, implicated in disease causation cannot be ruled out.

Epidemiology

The outbreak started in March 2019 when a cluster of cases emerged in the USA of patients who had developed lung injuries associated with using e-cigarettes. As of February 2020, more than 2800 patients had been admitted to various hospitals in the US due to an e-cigarette or vaping product use-associated lung injury (EVALI), with 68 deaths reported so far. Outside the US, Canada has reported a handful of cases.[4] 

Europe reported its first fatal EVALI case in March 2020.[5] Moreover, sporadic cases have been reported in travelers from the US to other countries.[6] The number of new cases has significantly declined in the US due to the banning of various vaping products and the emergence of the coronavirus 2019 (COVID-19) pandemic.[7] In the pediatric population, the occurrence of EVALI has been reported in patients as young as 13 years of age.[8]

Pathophysiology

The pathology of the disease is still poorly understood. A comprehensive pathophysiological basis for the lung injury seen in these patients is yet to be established. Butt et al., in a recent study, described a wide spectrum of histopathological findings seen in EVALI, including acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia, usually bronchiolocentric and accompanied by bronchiolitis.[9]

Previously, studies had suggested that EVALI may represent a form of exogenous lipoid pneumonia.[10] However, a recent literature review concluded that no histologic evidence of exogenous lipoid pneumonia was seen in the tissue samples. The histological findings are more likely suggestive of airway-centered chemical pneumonitis from one or more inhaled toxic substances found in the vapes. Testing for lipid-laden macrophages in bronchoalveolar lavage fluid samples using oil red O staining was previously thought to be a valuable marker of the disease process. However, the current consensus is that although common, this is an essentially non-specific finding.[11]

History and Physical

Patients with EVALI can present with a wide variety of symptoms within 90 days of using e-cigarette devices and related products and whose illnesses were not attributed to other causes. The constellation of symptoms ranges from respiratory such as cough, chest pain, and shortness of breath, which are most common, to gastrointestinal such as abdominal pain, nausea, vomiting, and diarrhea, to general symptoms, such as fever, chills, or weight loss. The main clinical manifestations are derived from 98 case-patients reported in 2020, predominantly men (79%) with a median age of 21 years.[12] A thorough history is crucial to establishing the diagnosis focusing on the acuity of symptoms. The CDC recommends obtaining detailed information during the patient interview regarding the type of vaping device used, type of substance used, frequency of vaping, and where the e-cigarette or vaping products were obtained.[13]

Most patients report using products from informal sources, including friends, family, and online or in-person dealers. Knowing the particular substance used is noteworthy, as most EVALI patients report using THC-containing products before the onset of symptoms. Maintaining confidentiality and a non-judgmental attitude are paramount in conducting a successful patient interview. Some patients may not be comfortable talking about their vaping product use, especially those who use THC or CBD products. On examination, the patient can present with fever (33%), tachycardia in (63%), and tachypnea (43%).[12] In addition, the patient's oxygenation is impaired, and 1:4 patients could have a pulse oxygen saturation of ≤88%. Physical examination should focus on vital signs, pulse oximetry, and a detailed chest examination, including auscultation for any added breath sounds. In addition, EVALI and COVID-19 signs and symptoms can be similar; therefore, clinical suspicion of EVALI is recommended during the COVID-19 pandemic.

Evaluation

Evaluation of patients is guided by the clinical presentation and severity of the patient's symptoms. All patients with a history of vaping product use in the last 90 days should at least get a chest X-ray, even if the symptoms are mild. Those having significant respiratory distress and low oxygen saturation (less than 95%) should be evaluated with a chest computed tomography (CT) scan if the suspicion of e-cigarette or vaping product use associated with lung injury (EVALI) is high. It is important to note that EVALI is a diagnosis of exclusion. Therefore it is necessary to rule out other possible causes of lung injury, such as viral pneumonia, community-acquired pneumonia, and any ongoing chronic inflammatory process that might affect the lungs.

Locally appropriate and clinically indicated diagnostic evaluation should be performed, including respiratory viral panel, influenza polymerase chain reaction or rapid test, RT-PCR for SARS-COV2, urine antigens of Streptococcus pneumoniae, and Legionella species., sputum culture, bronchoalveolar lavage, blood culture, and testing for HIV-related opportunistic infections.[1][14] 

Diagnostic imaging demonstrates a variety of radiographic presentations. Plain chest radiographs commonly show hazy bilateral opacities with central and peripheral sparing. Likewise, the most common CT finding is diffuse bilateral ground-glass opacities, with a basilar predominance and sometimes subpleural or lobular sparing.[15]

Laboratory evaluation should include a complete blood count with differential liver transaminases and inflammatory markers (e.g., erythrocyte sedimentation rate and C-reactive protein). Moreover, urine toxicology testing, with informed consent, including testing for THC, should be carried out on all patients. The primary role of bronchoscopy is to exclude alternative diagnoses, especially when the imaging findings are atypical and suggestive of an alternate etiology. Other potential candidates for bronchoscopy include patients with a high suspicion of infection, e.g., immunocompromised patients and those on invasive mechanical ventilation.

Treatment / Management

The mainstay of treatment for EVALI is supportive care. Supportive care usually includes supplemental oxygen to maintain oxygen saturation of 88 to 92 % via nasal cannula or high-flow oxygen or high-flow nasal cannula (HFNC). The severity of symptoms serves as a guide to whether the patient needs a hospital admission or can be managed on an outpatient basis. Respiratory distress, comorbidities that compromise pulmonary reserve, or decreased oxygen saturation (less than 95% while breathing room air) are strong indications that the patient will require hospital admission. If hypoxemia is severe, the management may require mechanical ventilation (26%) with a lung protective strategy simial to acute respiratory distress syndrome.[12] Rarely has ECMO been needed.

It is essential to rule out any infectious etiology by maintaining a high clinical suspicion for common respiratory pathogens. Early institution of therapy is key to the management of influenza and other infectious pathologies. Therefore, influenza testing should be strongly considered, particularly during the influenza season. Empiric antiviral or antimicrobial treatment should be considered by local antimicrobial resistance patterns. Patients with severe lung injury without any identifiable cause and a strong suspicion of EVALI have responded well to systemic corticosteroids.[16] However, the efficacy of this therapy has not been formally studied. Therefore, systemic glucocorticoids are recommended only for patients who meet the criteria for EVALI and have progressive symptoms and/or hypoxemia as a short course, starting with the equivalent of methylprednisolone 0.5 to 1 mg/kg per day or 40 to 60 mg of prednisone tapered over no longer than 14 days.[17]

There is limited evidence to support the use of corticosteroids in patients with milder symptoms being managed on an outpatient basis. Corticosteroids can potentially worsen an underlying respiratory infection; therefore, it is important to involve the pulmonologist when starting the patient on corticosteroids. These patients can deteriorate very rapidly and may end up requiring assisted mechanical ventilation.

When discharging patients with EVALI, it is crucial to ascertain the patient's clinical stability as dictated by stable oxygenation and exercise tolerance for 24 to 48 hours before planned discharge. These patients should follow up with their primary care provider or pulmonologist within 48 hours. Furthermore, follow-up testing with spirometry and chest X-ray may be required for some patients, as recommended by the pulmonologist.

Differential Diagnosis

Amid the pandemic caused by the deadly respiratory pathogen SARS-COV2, COVID-19 remains the topmost differential for any patient presenting to the emergency department with respiratory distress having bilateral infiltrates on the chest radiograph. Community-acquired pneumonia is another important consideration when dealing with a patient with significant respiratory symptoms, as it is quite common. EVALI is a relatively new disease, and there is a lot of confusion surrounding the diagnosis since it mimics the clinicopathologic presentation of various other pulmonary ailments. Nevertheless, the following patterns of lung injury have been reported with EVALI:

• Acute eosinophilic pneumonia
• Lipoid pneumonia
• Acute lung injury and acute respiratory distress syndrome
• Acute and subacute hypersensitivity pneumonitis
• Organizing pneumonia
• Acute eosinophilic pneumonia
• Diffuse alveolar hemorrhage
• Respiratory bronchiolitis-associated pneumonitis

It is noteworthy to remember that the pathologies mentioned above can present without a history of e-cigarette use and hence should be considered as a possible differential in the appropriate clinical context.

Prognosis

E-cigarette or vaping product use-associated lung injury (EVALI) is a potentially fatal disease, with 68 deaths reported as of this writing. A significant number of patients may end up requiring non-invasive or invasive mechanical ventilation. A recent study of 98 patients showed that as many as 76% of the cases needed supplemental oxygen, 22% required non-invasive ventilation (NIV), and 26% required intubation and mechanical ventilation.[12] Poor prognostic indicators include a patient age of more than 35 years, comorbidities that compromise pulmonary reserve, and patients presenting with resting oxygen saturation of less than 95%.[18] These patients can rapidly deteriorate and end up developing acute respiratory distress syndrome.

Complications

More than 50% of patients with EVALI require admission to the intensive care unit.[19] The main serious complications of EVALI are:

• Acute respiratory distress syndrome
• Respiratory failure
• Need for intubation and mechanical ventilation
• Death