E-cigarette or vaping product use–associated lung injury (EVALI) is defined as a rapidly developing inhalation-related pneumonitis associated with the use of electronic cigarettes. It was first described in the United States in 2019 following numerous outbreak-like episodes depicted mainly by acute respiratory failure associated with vaping use.1 It is characterized by a wide spectrum of radiologic and histologic patterns, most notably lipoid pneumonitis, organizing pneumonia, eosinophilic pneumonitis, hypersensitivity pneumonitis, diffuse alveolar damage, and acute respiratory distress syndrome (ARDS).2 Clinical presentation is nonspecific and similar to a respiratory infection, and the diagnosis is currently one of exclusion. This makes obtaining a thorough medical history essential to ensure a broad differential diagnosis that allows other causes to be ruled out.3 According to the U.S. Centers for Disease Control and Prevention (CDC), three criteria must be met4:

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  A history of vaping within 90 days prior to symptom onset.

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  Ground-glass opacities on chest computed tomography (CT) or chest radiograph.

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  Respiratory symptoms in the absence of pulmonary infection or an alternative diagnosis explaining lung injury.

Electronic cigarettes or vape devices emerged in China in 2003 with the aim of reducing tobacco consumption—one of the most important modifiable risk factors and a major threat to public health.5 The device heats a liquid stored in a tank using an electrical resistance, converting it into vapor. It reached the European market in 2006 and, one year later, the U.S. market. During the early years, regulation of its manufacture and commercialization was inadequate,6 which resulted in exponential market growth, with millions of units sold within a few years7 and more than 41 million users in 2018.8 The dramatic rise in popularity among adolescents was particularly striking, many of whom had never smoked before.9

According to the 2018 National Youth Tobacco Survey conducted in the U.S., 4.9% of students aged 11–14 years and 20.8% of those aged 15–18 years had used an electronic cigarette at least once in the previous 30 days.10 In Spain, according to the 2023 State Survey on Drug Use in Secondary Education (ESTUDES),11 54.6% of students aged 14–18 years had used a vape device at least once.

The substances contained in e-cigarette liquids cause toxicity in various organs, although pulmonary toxicity is the most evident.12 From 2019 through February 2020, a total of 2807 cases of EVALI were diagnosed in the United States, 75% of them in individuals younger than 35 years.4 This condition is more common in young people, with a mean age of 24 years. Mortality is scare (2.42% in the U.S. up to February 2020) but higher in older patients, with a mean age of 49.5 years among those who died.4 A total of 60 deaths have been confirmed across 27 states and the District of Columbia.4

Due to its recent emergence, information about vaping-related toxicity is still limited, especially in the context of critically ill patients. Its widespread use in the general population, particularly among young people, underscores the importance of conducting this article to summarize current knowledge on EVALI and the health consequences of vaping.

The aim of this narrative review is to summarize the available literature on EVALI—its pathophysiology and clinical syndrome—as well as diagnostic and therapeutic options, with a focus on critically ill patients.

We conducted a narrative review of the scientific literature with the objective of describing current knowledge regarding EVALI. Although methodological guidelines specific to systematic reviews (such as PRISMA) were not strictly followed, strategies were adopted to ensure breadth and relevance in the selection of the literature.

After applying the selection criteria, of the total number of records identified (n = 298), 75 articles were eventually included in the final review, the oldest being from 2010 and the most recent from 2023. The types of studies analyzed were as follows: one systematic review (1.33%), two randomized crossover clinical trials (2.66%), two prospective observational studies (2.66%), five retrospective observational studies (6.66%), five cross-sectional studies (6.66%), one case–control study (1.33%), six in vitro experimental studies (8%), six case series (8%), two single case reports (2.66%), 15 narrative reviews (20%), and one editorial (1.33%). Notably, 29 studies are currently ongoing (38.66%). Most were conducted in the United States. The main articles used for this review are summarized in Table 1.

The included studies were thematically grouped into 5 categories: systemic toxicity, clinical features of EVALI, diagnosis, treatment, and ongoing studies.

• 1

  Pulmonary and systemic toxicity due to electronic cigarettes. Pathogenesis of EVALI

  • a

    Main components of electronic cigarettes

The main components of electronic cigarettes are solvents such as propylene glycol and vegetable glycerin, psychoactive compounds—predominantly nicotine and delta-9-tetrahydrocannabinol (THC)—as well as various flavoring agents.

Propylene glycol and vegetable glycerin act as irritants when heated and inhaled. They increase the risk of respiratory infections and worsen pre-existing conditions such as asthma or chronic obstructive pulmonary disease.13 Both can alter pulmonary surfactant and induce an inflammatory response.14

Vitamin E acetate, a synthetic form of this compound,15 is considered one of the main agents responsible for EVALI.16 It causes pulmonary inflammation, and its combustion produces other irritating and toxic compounds such as carbonyls and quinones.17

Nicotine, a psychoactive compound, causesan obstructive effect on the airways18 and acts on dopamine-releasing centers, generating a potent addictive effect19 whichis stronger in younger individuals.20

Moreover, heating vaping liquids generates toxic substances classified as carcinogenic, such as nitrosamines, certain heavy metals, polycyclic aromatic hydrocarbons, and formaldehyde.21

Two flavoring agents—diacetyl and 2,3-pentanedione—alter gene-expression pathways related to cilia and the cytoskeleton in normal human bronchial epithelial cells.22

• • b

    Systemic toxicity of vaping

A possible association has been described between inhaled nicotine consumption and seizures in adolescents and young adults,23 as well as memory or behavioral disturbances.12

From a cardiovascular standpoint, vaping has been associated with palpitations, chest pain, various arrhythmias, and coronary artery disease.24 There is emerging evidence of increased cardiovascular risk associated with chronic vaping; however, evidence remains limited and is based mainly on preclinical studies, as no study with adequate long-term follow-up has yet been published.25 Moreover, preclinical studies25 suggest an increased risk of angina and acute myocardial infarction. Mohammadi et al.26 analyzed endothelial function in non-users, tobacco smokers, and e-cigarette users, concluding that e-cigarettes and tobacco smoking trigger different molecular responses. The study established an association between chronic e-cigarette use and increased inflammation and oxidative damage, leading to endothelial dysfunction and increased microvascular permeability, thereby raising cardiovascular risk similarly to tobacco smoking.26

Currently, a wide variety of studies are underway to evaluate long-term toxicity, particularly at the cardiopulmonary level (Table 2).

Vaping compounds act as irritants or toxins in the airway, generating an inhalation pneumonitis. Its use has been associated with various respiratory diseases,27 including asthma in previously non-smokers.28

• • c

    Pathogenesis of EVALI

EVALI is a syndrome caused by an acute pulmonary inflammatory reaction in response to toxic substances contained in e-cigarette liquids. It involves damage to the alveolar–capillary membrane, resulting in increased permeability, recruitment of inflammatory cells, and alveolar collapse.29

The cause of the syndrome is still unclear. Vitamin E acetate has been linked to the formation of lipid-laden “foamy” macrophages that cause inflammatory lung injury; it is also associated with surfactant dysfunction.30 Toxic effects on alveolar macrophages lead to increased reactive oxygen species and inflammatory cytokines, as well as enhanced apoptosis and necrosis.31 Furthermore, severe inflammatory responses and edema may result from the pyrolysis products of vitamin E acetate rather than the original compound per se.2

Similarly, other components have been associated with changes at cellular level, such as impaired protein synthesis, gene expression, and mitochondrial function. In the bronchial epithelium, ciliary function is altered.32

The use of vitamins as ingredients or additives is prohibited in Europe,33 which may explain the lower prevalence of EVALI in European countries vs the United States. Only 1 case originating in Europe has been documented—in Belgium in 2019—which resulted in death.34 However, the cellular and molecular mechanisms involved in the pathogenesis of EVALI remain incompletely understood.15

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  Clinical syndrome in patients with EVALI

• a

  Clinical signs

As with the underlying pathophysiology, the clinical course of the disease remains uncertain. This syndrome typically presents with respiratory, constitutional, and GI symptoms, with a mean duration of seven days. The most common respiratory symptoms are cough, dyspnea, chest pain, and occasionally hemoptysis. GI symptoms include nausea, vomiting, abdominal pain, and diarrhea. Fever, weight loss, headache, myalgias, or fatigue may also occur.27,35 Among patients requiring admission to the Intensive Care Unit (ICU), initial symptoms were gastrointestinal in 76.1%, respiratory in 96.8%, and constitutional in 92%.36

Over the course of the disease, a high percentage of patients develop respiratory failure. Severe cases progress similarly to ARDS, requiring ICU admission and invasive mechanical ventilation (IMV).27

Less common presentations include acute eosinophilic pneumonia and diffuse alveolar hemorrhage.8 Among complications, the most notable is the air-leak syndrome, which may manifest as pneumothorax or pneumomediastinum.37

• b

  Additional tests

Diagnosing EVALI is challenging. Symptoms are highly nonspecific, necessitating a broad differential diagnosis for respiratory failure. Laboratory findings and imaging studies are heterogeneous and resemble other diseases with similar clinical features. This requires a high index of suspicion and a diagnosis of exclusion, including a history of vaping use in clinical assessment. At present, no specific or pathognomonic signs are known.

Laboratory testing typically shows nonspecific inflammatory markers. Microbiological studies are negative. Bronchoalveolar lavage reveals inflammation with increased neutrophils and macrophages and, in a high percentage of cases, vitamin E acetate is detected in the sample.27,35

Lung biopsy is not required for diagnosis. Findings are heterogeneous and may be influenced by prior treatments. Common findings include diffuse nonspecific inflammation, lipid-laden macrophage infiltrates, diffuse alveolar damage with bronchiolocentric distribution, and interstitial granulomatous pneumonitis. Small-airway injury with bronchiolitis may also be observed.38,39

Radiologic imaging in EVALI—both chest X-ray and CT—is variable. The most common pattern is organizing pneumonia with diffuse bilateral ground-glass opacities predominantly in the basal regions and patchy areas of consolidation. Subpleural, peribronchovascular, and lobular parenchyma are often preserved. A small proportion of patients may show nodules, mainly in the upper lobes.40,41

The most severe lesion described—associated with the highest mortality rate40—is diffuse alveolar damage with ground-glass opacities, consolidation with volume loss, and alveolar collapse with bronchial dilation. Histology shows alveolar edema, hyaline membranes, and interstitial proliferation or fibrosis.40

Other possible findings include interlobular septal thickening with a “crazy-paving” pattern, reversed halo sign, bilateral pleural effusion, mediastinal or hilar lymphadenopathy, pulmonary edema, and areas of fibrosis.27,40

Fig. 1 illustrates a diagnostic algorithm for EVALI.

Figure 1.

Diagram representing an algorithm of the diagnostic process for e-cigarette or vaping-associated lung injury (EVALI).

PE: physical examination; BAL: bronchoalveolar lavage; CRP: C-reactive protein; AT: additional tests; CT: computed axial tomography.

Table 3 summarizes ongoing studies investigating the diagnosis of EVALI.

• 2

  Treatment of EVALI

Initial treatment is empirical, including even empirical antibiotic therapy until infectious causes are excluded, and is fundamentally based on supportive measures.

Corticosteroids may be beneficial due to their anti-inflammatory effect. Among the 140 cases reported to the CDC in 2019 that received corticosteroids, 82% improved.42 The dose and duration of treatment are not established; no clinical trials have compared different dosing regimens, and they vary across case series. In the report of a 23-year-old patient with EVALI requiring high-flow nasal cannula (HFNC), 60 mg of prednisone per day followed by a taper over 2 weeks was administered.43 In another observational study, prednisone doses ranged from 40 to 60 mg for five to ten days.1 This regimen is heterogeneous even within the same department; in a retrospective study carried out in a pediatric ICU in Philadelphia,44 corticosteroid doses ranged from 30 to 60 mg with administration schedules between six and 24 h. Total treatment duration ranged between five and 21 days. In general, dosing is individualized according to severity, in collaboration with other services such as pulmonology.42,45 In some cases, delaying initiation until infectious disease has been excluded is advisable. Their use is based on observational studies with high heterogeneity; no clinical trial has demonstrated efficacy and since the natural progression of the syndrome is unknown, the improvement attributed to steroids may be related to other measures such as cessation of e-cigarette use.42,45 No ongoing study registered on clinicaltrials.gov is evaluating the role of corticosteroids or their dosing.

In cases of severe respiratory failure, IMV may be necessary and even veno-venous extracorporeal membrane oxygenation (V-V ECMO).27,42 A case of an adolescent requiring lung transplantation has been described.46 In the study by Layden et al.,27 98 patients with EVALI were followed, of whom 25 required IMV and 2 died. Blagev et al.⁴⁷ followed 60 patients, of whom 10 required IMV and 2 died.

In a retrospective observational study conducted by the CDC across 50 states, the District of Columbia, Puerto Rico, and the United States Virgin Islands from August 2019 to January 2020, health records of hospitalized patients with confirmed or probable EVALI were analyzed.36 A total of 2708 patients were included, of whom 705 (44%) required ICU admission. Of these, 97.7% showed bilateral parenchymal involvement on CT. Among ICU patients, 41.4% received non-invasive ventilation or HFNC, and more than one-third required advanced respiratory support: 36.1% were placed on IMV and 6.7% required V-V ECMO. Survival data were available for only 656 patients, of whom 7% died. In this study, 99.2% of ICU patients received antibiotics and 6.1% antivirals. Almost all (91.6%) received corticosteroids. No data were collected on causes of death or presence of non-respiratory organ failure.

What is currently known about EVALI pathophysiology indicates that at the pulmonary level there is a significant and specific risk of ventilation-associated lung injury. This results from altered permeability in the distal bronchial tree and surfactant dysfunction. Areas of atelectasis develop that alter ventilation/perfusion ratios and lead to heterogeneous lung parenchyma prone to volutrauma. To avoid this, the use of ultra-protective ventilation strategies is essential in all patients requiring IMV.48 Pressure-controlled modes with low tidal volume (6 mL/kg ideal body weight), maintaining plateau pressure < 28 cmH₂O, and individualized PEEP titration ensuring a driving pressure < 15 cmH₂O are recommended. In patients with PaO₂/FiO₂ <150 mmHg, prone positioning should be considered. In severe ARDS that does not respond to these measures, early consideration of V-V ECMO is necessary, and if lung injury is irreversible due to EVALI, lung transplantation should be considered.36,48 Extracorporeal CO₂ removal systems may be required in certain circumstances.48 The role of V-V ECMO, whether as a bridge to lung transplantation or to recovery, is mainly to prevent IMV-induced lung injury, as it allows the use of ultra-protective ventilation while maintaining adequate gas exchange.49 A case has been described of a 19-year-old with EVALI presenting with a right pneumothorax requiring V-V ECMO to ensure ultra-protective ventilation.49 Cannulation occurred after one day of IMV, with a total IMV duration of eight days and V-V ECMO support for seven days. Length of stay went on for 13 days. Two weeks after discharge, chest X-ray and pulmonary function tests had normalized, with oxygen saturation at 100% without supplemental oxygen.

The importance of cessation of e-cigarette use has been described both for improved recovery and for preventing relapses or associated conditions.42,47

There are insufficient data regarding the syndrome’s prognosis, or whether IMV worsens its clinical course. Diffuse alveolar damage demonstrated on histology and imaging has been associated with mortality.40

Sequelae are uncertain, and long-term vital or functional prognosis is unknown. It has not been studied whether corticosteroid therapy decreases residual abnormalities or improves prognosis.27 In their case series, Aberegg et al.45 describe follow-up 11–28 days after discharge in which all patients improved, though residual symptoms were common. Pulmonary function tests showed mildly reduced predicted diffusing capacity. Between 2019 and 2021, a prospective observational study conducted in Utah, Idaho, and Nevada included a total of 73 patients with EVALI, 41.1% of whom required ICU admission.50 At 12 months, 39.1% had cognitive impairment, 48.4% respiratory impairment, and 59.4% symptoms of anxiety or depression. Post traumatic stress disorder (PTSD) symptoms occurred in 61.9%. No association was found between ICU admission and cognitive impairment, dyspnea, or mood-related symptoms. Severe dyspnea was present in 18.8% at 12 months, with an mMRC score increase from two to four, although pulmonary function tests were normal. After EVALI diagnosis, nicotine e-cigarette use decreased from 61% to 28% and THC vaping from 81% to 18.8%, but only 37.5% discontinued vaping and/or smoking.

Awareness of the harmful effects associated with vaping makes implementation of public health measures essential. Education of at-risk populations is vital. Most ongoing studies evaluate prevention or cessation strategies, mainly targeting adolescents and young adults, considered at-risk populations (Tables 4 and 5). Socially, vaping is more accepted than tobacco use, reinforcing the erroneous view of vaping as a "healthier substitute." Recently, public policies such as increasing taxes on e-liquids have begun, although vaping in enclosed spaces such as bars or nightclubs has not yet been prohibited.51

This review addresses a highly relevant current topic, given the marked increase in e-cigarette use in recent years, especially among young people. It offers a general, integrative overview of updated literature on toxic effects of vaping components, and highlights EVALI as a severe and potentially fatal condition caused by their use.

In addition, it identifies areas of greatest uncertainty, opening paths for future research. There is a need for longitudinal studies assessing chronic vaping’s toxic effects—particularly pulmonary and cardiovascular—as an emerging risk factor. Regarding EVALI, diagnostic performance must be improved and adequate, effective treatment implemented, which requires deepening understanding of underlying pathophysiology. Evaluating the role of corticosteroids in both acute illness and long-term sequelae is essential, as is defining appropriate dosing and duration.

The main limitation of this review derives from the studies included, most of which are observational and retrospective.

E-cigarettes are the main determinant of EVALI, an inhalation pneumonitis causing a severe and potentially fatal respiratory disease. This process has emerged recently, in the context of widespread vaping over the past two decades. There are still no conclusive data; pathophysiology is uncertain, diagnosis is exclusionary, and therapeutic strategies are highly heterogeneous due to lack of standardization and protocols. Prognostic and long-term outcome data remain insufficient.

It is necessary to design longitudinal studies evaluating chronic exposure effects and randomized clinical trials addressing EVALI treatment.

Educational and public health interventions are essential to positively influence vulnerable populations (especially youth), raising awareness of the health risks linked to e-cigarette consumption.

All authors contributed to study conception and design. ACC and ISG jointly conducted updated literature review and manuscript drafting. JMPV and ACCruz conducted the critical revision of the final document.

None declared.

No AI software or tools were used.