CONTENTS
- Rapid reference 🚀
- Basics
- Epidemiology
- Clinical presentation
- Radiology
- Laboratory testing
- Bronchoscopy
- Diagnostic approach
- Treatment
- Prognosis
- Podcast
- Questions & discussion
- Pitfalls
This section describes an approach to a patient with probable EVALI who doesn't require intubation. The approach to an intubated patient would be similar but with a lower threshold to pursue bronchoscopy. Please note that this is not based on high-level evidence (none exists).
rough criteria for patients with probable EVALI:
- Recent history of vaping (especially concerning if using THC oils or adulterated vape liquids).
- Bilateral ground-glass opacities on CT scan (without atypical features, such as cavitation, large nodules, or lobar consolidation).
- No immunocompromise.
- No exposure to unusual pathogens.
- Medically uncomplicated patient (e.g., no connective tissue or lung disease history).
initial noninvasive diagnostic/therapeutic approach
- Noninvasive diagnostic evaluation:
- ✅ Sputum gram stain and culture (if productive cough).
- ✅ Blood cultures x2.
- ✅ Urine legionella & pneumococcus antigens.
- ✅ Nares PCR for MRSA.
- ✅ Nasopharyngeal swab for viral pathogens (COVID, influenza, and other respiratory viruses).
- ✅ HIV serology.
- ✅ C-reactive protein and procalcitonin.
- ✅ Complete blood cell count with differential (to evaluate for eosinophilia).
- Empiric therapy for community-acquired pneumonia & EVALI:
- Antibiotics (e.g., ceftriaxone plus azithromycin).
- Oxygen support as needed.
- Steroid (e.g., 1 mg/kg prednisone daily).
follow-up
- If clinical improvement & diagnostic evaluation are unremarkable:
- Gradually wean off the steroids.
- Finish a treatment course of antibiotics (although the beta-lactam may be discontinued if the procalcitonin level is low and concern is low for pneumonia).
- If there is no clinical improvement or if laboratory evaluation is worrisome (e.g., HIV-positive):
- Consider bronchoscopy.
- Additional therapies and laboratory studies as clinically warranted.
- There was a large outbreak of EVALI in 2019 due to the use of Vitamin E acetate as a diluent for tetrahydrocannabinol (THC)-containing vaping products. This led to heightened awareness of the possibility of EVALI.
- However, EVALI isn't a single disorder. Instead, vaping has been associated with various forms of lung injury (which shouldn't be surprising, given the broad range of chemicals present in different vapes). Among different patients, vaping can probably lead to various clinicopathological entities (including cryptogenic organizing pneumonia, acute eosinophilic pneumonia, and lipoid pneumonia).
- The tables below review case reports of EVALI tjat occurred before the 2019 outbreak. With improved regulation of vaping products, it's conceivable that future cases might resemble these pre-2019 cases.
epidemiology of the 2019 epidemic
- Most patients are young (average age ~20 years old), with a male predominance.
- ~80% of patients report a history of vaping with tetrahydrocannabinol (THC).
- ~94% of patients reported the use of vaping within a week of symptom onset.
presentation of patients during the 2019 epidemic
- Acuity
- Onset is usually subacute, with deterioration over a period of days (the median duration of symptoms before hospitalization was six days).
- About a third of patients are initially diagnosed with mild pneumonia and discharged home with oral antibiotics (e.g., azithromycin).
- Presenting symptoms:(31491072)
- 98% have respiratory symptoms:
- Dyspnea in 87%.
- Cough in 83%.
- Chest pain in 55%.
- Hemoptysis in 11%.
- 81% had gastrointestinal symptoms (nausea in 70%; vomiting in 66%; diarrhea in 43%; abdominal pain in 43%). These may initially be a predominant feature of the illness.
- 100% of patients had some constitutional symptom (fever in 81%; chills in 58%; weight loss in 25%; fatigue/malaise in 45%).
- 40% had headache.
- Upper respiratory symptoms (e.g., rhinorrhea, sneezing, or congestion) don't seem to be a component of the illness.
- 98% have respiratory symptoms:
EVALI isn't a homogeneous entity. Patients may have a variety of different radiographic findings, although they do have some similarities:
CT scan – general characteristics of EVALI
- Common features:
- Bilateral, ground-glass opacities.
- Often sparing of the subpleural lung periphery.
- Features that shouldn't be seen (if present, these may be a red flag that EVALI isn't the correct diagnosis)
- 🚩 Dense lobar consolidation.
- 🚩 Dense nodules.
- 🚩 Cavitation or necrosis of lung tissue.
radiographic features – 2019 outbreak
- Chest X-ray will generally show bilateral infiltrates (~90% of cases), although these may be absent early in the disease course.
- CT scanning invariably shows bilateral ground-glass opacities. Subpleural sparing may also be seen in more typical cases.
- However, various patterns may be seen. Additional findings that have been noted include pleural effusions, pneumomediastinum, and tree-in-bud opacities.

EVALI with AEP (acute eosinophilic pneumonia) predominant pattern
- Bilateral, ground-glass opacities.
- Smooth septal thickening is often seen.
- Pleural effusion(s) may be seen.

EVALI with an organizing pneumonia (OP) predominant pattern
- Bilateral, ground-glass opacities.
- Organizing pneumonia can generate diverse findings on the chest CT, making defining a stereotypical pattern challenging. The following patterns have been reported:
- (a) Sparing of the lung periphery (this pattern may be seen with various types of inhalation lung injury).
- (b) Multiple ground-glass nodules distributed in a centrilobular pattern.

EVALI with a lipoid pneumonia predominant pattern
- Bilateral, ground-glass opacities.
- Crazy paving may be seen. This refers to the patchy involvement of some lobules, which are adjacent to un-affected lobules. Septal thickening may accentuate the borders between normal lobules and diseased lobules.

Please note that with increasingly diverse vape products, individual patient's laboratory values may vary in the future.
laboratory abnormalities reported in the 2019 outbreak:
- CBC:
- Acute phase reactants
- Erythrocyte sedimentation rate (ESR) of >30 mm/hr was seen in 93% of patients. This may be severely elevated (>100 mm/hr), which may incorrectly raise concern for vasculitis.
- C-reactive protein (CRP) is often elevated at 20-30 mg/dL. (31491073)
- Procalcitonin had a median of 0.58 ug/L (with an interquartile range of 0.35-1). (31491072)
- Bronchoalveolar lavage results:
- There was often a neutrophilic predominance (with a median of 65% neutrophils).
- Eosinophilia generally wasn't a feature (median 0% eosinophils, interquartile range 0-6%)
- Lipid-laden macrophages were often seen on Oil Red-O stain, but not in all cases. (31491072)
bronchoscopy is often unnecessary
- The primary goal of bronchoscopy is to exclude alternative diagnoses (especially infection) rather than to find any specific pathognomonic feature of EVALI.
- Bronchoscopy may not be needed in patients with typical imaging features and no competing diagnosis. Likewise, if the diagnosis can be narrowed down to EVALI versus community-acquired pneumonia, then it's possible to empirically treat both processes (as discussed further in the section below).
- Decisions regarding bronchoscopy may also be influenced by how well the patient would likely tolerate this procedure.
potential indications for bronchoscopy may include
- Substantial immunocompromise.
- Imaging features suggest an alternative diagnosis (e.g., nodular or cavitary lesions on CT scan).
bronchoscopic findings in EVALI
- Bronchoscopic findings may vary, depending on the various types of lung disease that may occur (noting that EVALI isn't a single discrete entity).
- Patients with acute eosinophilic pneumonia may have eosinophilia noted in the bronchoalveolar lavage.
- During the 2019 EVALI outbreak, many patients were found to have lipid-laden macrophages (aka, “foamy macrophages”). These may support a diagnosis of EVALI but aren't entirely specific for it.
- EVALI is a diagnosis of exclusion. Therefore, due diligence should always be invested in considering alternative diagnostic possibilities.
- In younger patients without other medical problems, the differential diagnosis will often boil down to pneumonia vs. EVALI. A reasonable initial approach is often empiric therapy with antibiotics plus steroids (especially given that steroids are often beneficial for community-acquired pneumonia anyway 📖). Antibiotics may often be discontinued with the return of additional test results (e.g., procalcitonin).
antibiotics
- Empiric antibiotics are often provided initially until pneumonia may be excluded.
- (Antibiotics are not indicated if a firm diagnosis of EVALI has been secured.)
steroid
- Many reports suggest that steroid is beneficial (although there is obviously no solid proof that steroid causes benefits).
- The ideal dose of steroids is unclear. ~1 mg/kg/day methylprednisolone generally seems reasonable, although some authors have reported using doses as high as 500 mg/day methylprednisolone. (31491073, 31513559) Patients hospitalized but not critically ill might benefit from lower doses (e.g., 40 mg/day prednisone). (34481602)
respiratory support
- Noninvasive ventilation or high-flow nasal cannula may be used as clinically warranted.
- Intubation may be required in about a third of cases. (31491072)
- A few deaths have been reported, but the overwhelming majority of patients have survived. Improvement often occurs over a period of days.
- If improvement doesn't occur, re-consider the diagnosis.
- The investigation is similar to the approach to non-resolving pneumonia, as explored further here: 📖.
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- Failure to obtain a history regarding vaping and to consider this as a potential cause of respiratory failure. Ideally, this history should also include whether the patient is adulterating their own vaping liquid (which might increase the risk of VAPI).
- The assumption that every patient with possible vaping-induced pulmonary injury requires an invasive evaluation (bronchoscopy and potentially surgical lung biopsy).
Guide to emoji hyperlinks 
= Link to online calculator.
= Link to Medscape monograph about a drug.
= Link to IBCC section about a drug.
= Link to IBCC section covering that topic.
= Link to FOAMed site with related information.
- 📄 = Link to open-access journal article.
= Link to supplemental media.
References
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