EVALI (Electronic Cigarette or Vaping Product Use–Associated Lung Injury): Comprehensive Expert Review

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EVALI Lung Injury: Pathophysiology, Imaging Diagnosis, Treatment, and Prognosis of Electronic Cigarette–Associated Lung Disease

Introduction

Electronic cigarettes and vaping devices have transformed nicotine and cannabis consumption worldwide. However, this transformation has come with a significant public health cost: EVALI (Electronic cigarette or vaping product use–associated lung injury). Since the 2019 outbreak in the United States, EVALI has become a globally recognized clinical-radiologic entity. It represents a complex inflammatory lung injury syndrome linked primarily to vaping products, especially THC-containing cartridges adulterated with vitamin E acetate.

EVALI lung injury is now considered a distinct clinicopathologic syndrome characterized by acute lung injury, systemic inflammation, and characteristic radiologic patterns. Understanding its pathophysiology, epidemiology, clinical presentation, imaging features, differential diagnosis, diagnostic criteria, treatment strategies, and prognosis is essential for clinicians, radiologists, pulmonologists, emergency physicians, and medical students.

This expert-level column provides a comprehensive, literature-based, world-class analysis of EVALI using the attached clinical case and imaging as a foundation.

Pathophysiology of EVALI

The pathophysiology of EVALI is multifactorial and toxic-inflammatory in nature. The strongest mechanistic evidence implicates vitamin E acetate (tocopherol acetate), widely used as a thickening agent in illicit THC vaping cartridges.

Mechanisms of Lung Injury

  1. Surfactant Disruption: Vitamin E acetate interferes with alveolar surfactant, increasing surface tension and causing alveolar collapse.

  2. Direct Chemical Toxicity: Heating vitamin E acetate generates ketene gas, a highly reactive pulmonary toxin.

  3. Oxidative Stress: Aerosolized lipid compounds induce reactive oxygen species and alveolar epithelial injury.

  4. Immune Activation: Macrophage activation and cytokine release cause diffuse inflammatory lung injury.

  5. Lipid-Laden Macrophages: Accumulation within alveoli contributes to impaired gas exchange.

Histopathology demonstrates:

  • Diffuse alveolar damage (DAD)

  • Acute fibrinous organizing pneumonia (AFOP)

  • Organizing pneumonia (OP)

  • Bronchiolocentric inflammation

  • Alveolar edema

These findings align with the imaging patterns seen on HRCT.

Epidemiology

  • First outbreak: June 2019, USA

  • Peak incidence: September 2019

  • CDC-reported cases (Jan 2020): 2,602 cases, 57 deaths

  • Strong association with THC vaping products

  • The majority of patients: young to middle-aged adults

  • Increasing global recognition due to international vaping markets

Clinical Presentation

EVALI presents as a subacute inflammatory syndrome:

Respiratory symptoms

  • Dyspnea

  • Cough

  • Chest pain

  • Hypoxemia

Systemic symptoms

  • Fever

  • Fatigue

  • Weight loss

Gastrointestinal symptoms

  • Nausea

  • Vomiting

  • Diarrhea

Laboratory findings often include:

  • Leukocytosis

  • Elevated CRP/ESR

  • Negative infectious workup

Imaging Features

Figure 1. Chest X-ray at Presentation (AP Semi-erect)

Initial AP chest radiograph showing bilateral lower lung predominant airspace opacities.


Figure 2. Chest X-ray after 2 Days (AP Semi-erect)

Rapid progression of bilateral airspace opacities indicates evolving inflammatory lung injury.


Figure 3. Chest CT (HRCT Multiplanar)

A: Centrilobular ground-glass opacities with mild septal thickening (apical regions)

B: Geographic bilateral ground-glass opacities with subpleural sparing

C: Lower-lobe predominant ground-glass opacities with lobular preservation

D: Mild hilar lymphadenopathy and trace bilateral pleural effusions

Classic EVALI pattern with lobular and subpleural sparing, diffuse GGO, septal thickening, and inflammatory distribution.


Figure 4. Chest X-ray 3 Days After CT

Marked improvement of parenchymal opacities following steroid therapy.

Differential Diagnosis

  • Atypical pneumonia (including COVID-19)

  • Cryptogenic organizing pneumonia (COP)

  • Pulmonary vasculitis (e.g., EGPA, MPA)

  • Alveolar hemorrhage

  • Eosinophilic pneumonia

  • Acute interstitial pneumonia

  • Diffuse alveolar damage

Diagnosis

Diagnosis of EVALI is clinical-radiologic-exclusionary:

Diagnostic Criteria

  1. Vaping exposure within 90 days

  2. Pulmonary infiltrates on imaging

  3. Negative infectious workup

  4. No alternative plausible diagnosis

This case fulfills all CDC diagnostic criteria.

Treatment

Core Management

  • Immediate cessation of vaping

  • Systemic corticosteroids

  • Oxygen therapy

  • Supportive care

  • Monitoring for respiratory failure

Most patients show rapid radiologic and clinical improvement with steroid therapy.

Prognosis

Short-term

  • High recovery rate with early treatment

  • Rapid imaging resolution

Long-term

  • Potential fibrosis

  • Reduced DLCO

  • Chronic dyspnea

  • Risk of relapse with re-exposure

Prognosis is excellent with early recognition and treatment.

Quiz

Question 1. A patient with recent THC vaping presents with dyspnea, fever, bilateral ground-glass opacities, and a negative infection workup. Most likely diagnosis?

A. COVID-19 pneumonia
B. EVALI
C. Pulmonary embolism
D. Sarcoidosis

Answer: B. Explanation: Vaping history + GGO + negative infection = EVALI.

Question 2. Which imaging feature is most characteristic of EVALI?

A. Upper lobe cavitation
B. Subpleural sparing with diffuse GGO
C. Tree-in-bud nodules
D. Honeycombing fibrosis

Answer: B. Explanation: Subpleural sparing + diffuse GGO is classic EVALI pattern.

Question 3. Primary toxic agent strongly linked to EVALI?

A. Nicotine sulfate
B. Propylene glycol
C. Vitamin E acetate
D. Formaldehyde

Answer: C. Explanation: Vitamin E acetate detected in BAL fluid in most EVALI cases.

References

  1. Layden JE et al., “Pulmonary illness related to e-cigarette use in Illinois and Wisconsin,” NEJM, 2020.

  2. Blount BC et al., “Vitamin E acetate in BAL fluid associated with EVALI,” NEJM, 2020.

  3. Kligerman S et al., “Radiologic features of EVALI,” Radiology, 2020.

  4. Henry TS et al., “Imaging of vaping-associated lung disease,” AJR, 2020.

  5. Butt YM et al., “Pathology of vaping-associated lung injury,” AJSP, 2019.

  6. CDC, “Outbreak of lung injury associated with vaping,” 2020.

  7. Maddock SD et al., “Pulmonary lipid-laden macrophages in EVALI,” AJRCCM, 2019.

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