Vaping-associated lung disease

Vaping-associated lung disease, or EVALI (e-cigarette or vaping product use-associated lung injury), consists of patterns of inhalational pulmonary injury induced by electronic cigarettes (also known as e-cigarettes, e-vaporizers, e-hookahs, vapes, vape pens). These products heat up a liquid containing nicotine (in which case the device is formally also called an electronic nicotine delivery system (ENDS)) or cannabinoids (such as tetrahydrocannabinol or cannabidiol, in which case the process is also colloquially called "dabbing"). The user then inhales the aerosol generated.

Epidemiology

The incidence of lung illness among electronic cigarette users is unclear, but almost 3,000 hospitalized cases have been reported in the United States as of early 2020, with multiple deaths (67 had been confirmed in 29 of the states) ¹. Most cases involved use of both nicotine and cannabinoid products ². Most patients report last vaping in the week before symptom onset ³. A majority of affected patients are young (teens and 20s) and male ³.

Clinical presentation

Case series describe non-specific clinical features that include ^3-7,19,20:

• respiratory symptoms
  • shortness of breath
  • cough
  • chest pain
• constitutional symptoms
  • subjective fever and chills
  • fatigue
• gastrointestinal symptoms
  • nausea and vomiting
  • diarrhea
  • abdominal pain

These symptoms occur days to weeks prior to hospitalization, which is usually prompted by hypoxemia and, sometimes, progression to respiratory failure and acute respiratory distress syndrome ⁸.

Laboratory evaluation typically demonstrates leukocytosis with a neutrophilic predominance ³.

Pulmonary function tests (PFTs) are often consistent with an overall decrease in airflow and diffusing capacity. Airflow tends to improve post-recovery whereas diffusing capacity does not ²⁰.

Proposed surveillance case definitions from American public health authorities require the following criteria ⁸:

• use of an e-cigarette (vaping) or dabbing within 90 days prior to symptom onset
• pulmonary opacities on radiography or CT
• absence of pulmonary infection (demonstrated by locally appropriate and clinically indicated testing such as respiratory viral panel, influenza polymerase chain reaction or rapid test, urine antigens of Streptococcus pneumoniae and Legionella spp., sputum culture, bronchoalveolar lavage, blood culture, human immunodeficiency virus-related opportunistic infections)
• no evidence of other plausible diagnoses (e.g. cardiac, rheumatologic, or neoplastic process)

Pathology

Several pathologic patterns of lung injury have been reported in the setting of vaping ²:

• lipoid pneumonia (exogenous) ^4,7,13,14
• diffuse alveolar damage ^5,15​
• acute eosinophilic pneumonia ^5,11,12
• organizing pneumonia ¹⁰
• diffuse alveolar hemorrhage ⁶
• respiratory bronchiolitis interstitial lung disease ^9​
• ​hypersensitivity pneumonitis
• giant cell interstitial pneumonia ⁵

Etiology

The entity is likely caused by a chemical exposure (rather than an infectious agent), and the vast majority of cases have involved vaping products containing vitamin E acetate, which has been used as a thickening agent in the manufacture of illegal tetrahydrocannabinol-containing vapes ^1,21. 

Microscopic appearance

A frequent finding on bronchoalveolar lavage fluid is the presence of lipid-laden macrophages seen with oil red O staining ^4,7,13,15,16.

Radiographic features

Plain radiograph

The vast majority of patients have pulmonary opacities on chest radiograph ^3,8,18.

CT

The most common finding is diffuse bilateral ground glass opacities ^3,8,18, with a basilar predominance and sometimes subpleural or lobular sparing ^5,20. Specific patterns with radiologic-pathologic correlation are described separately:

• lipoid pneumonia ^4,7,13,14
  • basilar predominant ground glass opacities, nodular or tree-in-bud opacities, crazy paving
• diffuse alveolar damage ^5,15
  • dependent ground glass opacities and consolidation (acute/exudative phase), followed by reticulation and traction bronchiectasis (organizing/proliferative phase)
• acute eosinophilic pneumonia ^5,11,12
  • ground glass opacities and consolidation, often with pleural effusions and septal thickening
• organizing pneumonia ^10,20
  • peripheral or perilobular ground glass opacities and/or consolidation, sometimes with the atoll/reverse halo sign ¹⁸
• diffuse alveolar hemorrhage ⁶
  • ​centrilobular ground glass opacities, nodules, and/or consolidation with subpleural sparing, followed by septal thickening (reflecting lymphatic engorgement with blood products)
• respiratory bronchiolitis interstitial lung disease ⁹
  • ^​upper lobe predominant centrilobular ground glass nodules
• hypersensitivity pneumonitis ^5,20
  • ^​centrilobular ground glass nodules anteriorly, dependent confluent ground glass opacity and mosaic attenuation
• giant cell interstitial pneumonia ⁵
  • ^​fibrosis seen as peripheral reticulation, ground glass opacity, and traction bronchiectasis

Treatment and prognosis

Many patients treated with systemic corticosteroids show clinical improvement ^7,8.

History and etymology

Electronic nicotine delivery systems (ENDS) have been available in the USA since 2007, however the first case report was not published until 2013 ²⁰.

See also

• drug-induced lung disease
• recreational drug use (radiological manifestations)