EVALI: Vaping-Associated Lung Injury

Introduction

• "Vaping" heats a liquid or wax to create an aerosol, containing nicotine, cannabinoids, flavorings, and additives.
• Devices include electronic cigarettes, vape pens, and vape mods.
• EVALI, originally termed vaping-associated pulmonary injury, emerged in 2019.
• It presents as an acute or subacute respiratory illness, potentially severe and life-threatening.

Epidemiology

• EVALI was first recognized in the summer of 2019.
• Over 2800 hospitalized cases of EVALI reported to the CDC by February 18, 2020.
• 68 deaths were reported
• Data collection ceased in February 2020.
• 66% of reported cases were male, and nearly 80% were under 35, ranging from 13 to 85 years old.
• 22% of patients had underlying asthma.
• Emergency department visits, Google searches, and case reports confirmed similar trends, peaking between June and September 2019.
• Sporadic EVALI cases were reported in Europe and among travelers from the United States to Europe.

Pathogenesis and Risk Factors

• The exact pathogenesis of EVALI is not known
• It manifests as acute lung injury with acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia.
• It is usually bronchiolocentric and accompanied by bronchiolitis.
• It possibly reflects a spectrum of disease processes
• Vaping-associated lung diseases include acute eosinophilic pneumonia, diffuse alveolar hemorrhage, and lipoid pneumonia.
• Respiratory-bronchiolitis interstitial lung disease has also been reported as a potential manifestation
• No infectious etiology or bacterial contamination in e-cigarette fluids has been identified.
• Key risk factor is e-cigarette or similar product usage
• Bronchoalveolar lavage fluid (BAL) samples revealed tetrahydrocannabinol (THC) and/or vitamin E acetate in most cases.
• Nicotine, cannabinoid (CBD) oils, coconut oil, and limonene might also be involved.

THC

• 75 to 80% of EVALI patients reported using THC-containing products
• THC or its metabolites were found in 94% of EVALI patients versus none in healthy individuals.

Vitamin E Acetate

• Synthetic vitamin E acetate was initially identified in BAL samples from 29 EVALI patients across 10 states.
• 94% of EVALI patients had vitamin E acetate, compared to none in healthy individuals.
• The toxicity mechanism is unknown but linked to pyrolysis byproducts.

Nicotine

• 13 to 58% of EVALI patients used nicotine-containing products with or without THC in the 90 days before symptom onset.
• Nicotine or its metabolites were found in 64% of EVALI patients' BAL fluid versus none in healthy individuals.
• Nicotine was also found in BAL samples from asymptomatic tobacco or e-cigarette smokers.

Other Oils

• Other oils like CBD, plant oils, medium-chain triglycerides, petroleum distillates, and terpenes haven't been consistently found in products used by or BAL fluid from EVALI patients.

Devices

• Majority of affected individuals (among 573) obtained products from illicit or informal sources.
• Other patients reported using commercially available e-cigarette products or adding homemade liquids to cartridges or pods.
• Some dripped substances onto the heating element ("dripping"), while others used concentrated nicotine or THC in a waxlike substance ("dabbing").
• Mixing and heating active and inactive components may produce toxic new agents.

Comorbidities

• Unclear if comorbidities increase risk
• 68% had at least one comorbidity
• Asthma may be a risk factor

Animal Models

• An animal model of EVALI has been described and may shed light on the pathogenesis of the disease

Clinical Features

• Clinical data is based on a case series of 98 patients meeting EVALI criteria, with similar symptoms in other series, including adolescents.
• The median patient age was 21; 78% were male, and 68% had at least one comorbidity.
• No patients died during the initial hospital admission.
• Respiratory symptoms: shortness of breath (85%), cough (85%), chest pain (52%), pleuritic chest pain (36%), hemoptysis (8%).
• Constitutional symptoms: fever(84%) and chills (60%).
• Gastrointestinal symptoms: nausea (66%), vomiting (61%), diarrhea (44%), abdominal pain (34%)
• Rarely, gastrointestinal symptoms are the main symptom
• On examination: fever (33%), tachycardia (63%), tachypnea (43%).
• 58% were hypoxemic, with ≤88% oxygen saturation in 25%.
• Progression to respiratory failure is common

Presentation

• A cross-sectional study of 360 adolescents (13-17 years, 68% male), 859 young adults (18-24 years, 72% male), and 936 adults (25-49 years, 66% male) showed variations
• Over 90% of all patients had respiratory symptoms
• Gastrointestinal symptoms are more prevalent among adolescents (91%) and young adults (89%) than in adults (75.3%)
• Asthma history was more common in adolescents and young adults than adults: (44 and 41% versus 28%).

Evaluation

• Suspect EVALI in patients with a history of vaping or e-cigarette product use presenting with pneumonia-like syndrome, progressive dyspnea, and/or hypoxemia.
• Key questions to ask:
• Type of vaping device used?
• Products vaped (nicotine, THC, cannabidiol, flavored liquid)?
• Cartridge Reuse?
• Was the product concentrated?

Evaluation considerations

• When did vaping start relative to symptom onset?
• How often was the patient vaping?
• Did they perform the Valsalva maneuver?
• Smoking habits?
• Evaluation steps depend on illness acuity, other exposures (influenza, COVID-19), and underlying diseases (heart failure, asthma).

Laboratory Evaluation

• Designed to exclude differential diagnoses such as community-acquired pneumonia and COVID-19
• Typical tests include: complete blood count, blood urea nitrogen, and creatinine.
• Liver function tests if GI symptoms are present
• Microbiologic testing depends on severity of respiratory impairment

Biomarkers

• The utility of biomarkers (C-reactive protein and procalcitonin) is not routinely investigated.
• A single-center study of 24 EVALI patients noted elevated markers of coagulation (INR) and inflammation (CRP, ESR, procalcitonin), although the significance is uncertain.

Imaging

• 83% have abnormal chest radiograph
• Diffuse hazy or consolidative opacities.
• Progressive dyspnea or hypoxemia, consider CT pulmonary angiography
• (CTPA) to exclude pulmonary embolism
• High-resolution CT (HRCT) w/o risk factors of pulmonary embolism

Imaging Results

• Bilateral opacities are typical
• A series of 98 patients, bilateral opacities were noted in 100 percent on radiograph
• The opacities are ground glass
• Subpleural space can be spared
• Pleural effusions were less common (approximately 10%)
• Features consistent with diffuse alveolar damage

Radiographic Patterns

• Diffuse alveolar damage results in Dependent consolidation, diffuse ground glass, air bronchograms.
• Acute eosinophilic pneumonia-Nodular areas of consolidation, diffuse ground glass, septal thickening, small amount of pleural fluid
• Hypersensitivity pneumonitis-Centrilobular ground glass opacities anteriorly and more confluent ground glass opacities in dependent areas, and lobules of mosaic attenuation
• Organizing pneumonia: Diffuse, multifocal discrete and confluent.
• Lipoid Pneumonia: Ground glass and consolidative opacities in dependent portions of the lungs with fat attenuation

Pathogens

• Community-acquired pneumonia (CAP); exclude CAP when evaluating a patient with suspected EVALI because prompt directed antimicrobial.
• Presentation of CAP overlaps with EVALI; ranges from mild pneumonia with fever and productive cough to severe pneumonia with acute respiratory distress syndrome and sepsis.
• COVID-19: COVID-19: cause of CAP has clinical features to EVALI such as cough, dyspnea, fever, and diarrhea

Organizing Pneumonia

• Diffuse interstitial lung disease (ILD) - affects the distal bronchioles, respiratory bronchioles, alveolar duct, and alveolar walls, has been reported in a few patients after use of e-cigarettes
• Hypersensitivity Pneumonitis: Vaping can cause HP if supportive information is limited; in the differential diagnosis of lung zone opacities with centrilobular nodules that are seen in EVALI

Diffuse Alveolar Hemorrhage

• DAH is a consequence of e-cigarettes
• 1 patient developed dyspnea, hemoptysis, and hypopxemia after frequent vaping with solutions and CT revealing patchy areas of consolidation
• Treatment with pulse dose steroids led to radiographic clearing after two weeks

Treatment Considerations

• It is important to ensure to test for community-acquired pneumonia (CAP), including COVID-19, is not overlooked because infectious pneumonias are much more common than EVALI
• Hospitalization is advisable for any patient with suspected EVALI who has respiratory distress, decreased oxygen saturation (<95 percent on room air), significant comorbidity, and/or suboptimal access to follow-up within 24 to 48 hours