E-Cigarette or Vaping Product Use-Associated Lung Injury

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An acute inhalational lung injury caused by use of e-cigarette or vaping products, recognised as a distinct entity during a 2019 outbreak in the United States. Most cases were associated with vaping tetrahydrocannabinol-containing products obtained from informal sources, and vitamin E acetate used as a diluent in those products is the agent most strongly implicated. Patients present with respiratory, gastrointestinal and constitutional symptoms together, with bilateral pulmonary opacities on imaging and no identified infection.

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1
Mappings
1
Definitions
5
Pathophys.
1
Histopath.
12
Phenotypes
2
Hypotheses
1
Gaps
10
Pathograph
3
Medical Actions
1
Models
1
Deep Research
🔗

Mappings

ICD-10-CM
ICD10CM:U07.0 Vaping-related disorder
skos:exactMatch
semapv:ManualMappingCuration
📘

Definitions

1
Outbreak surveillance case definition
Three conjoined criteria: vaping exposure within 90 days, pulmonary infiltrates on imaging, and exclusion of alternative causes. It is a definition of exclusion built around an exposure history, with no confirmatory test, which is why the diagnosis depends on asking about vaping at all.
CASE_DEFINITION
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes."
States the operative case definition in the authors' own words. Its third limb does the most work and is the least visible: illnesses "not attributed to other causes" makes this a diagnosis of exclusion, so its performance depends on how hard alternatives were sought.
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Mechanistic Hypotheses

2
Intact vitamin E acetate disrupts alveolar surfactant
vea_surfactant_route CANONICAL
The default model this entry's pathograph is drawn against: inhaled vitamin E acetate reaches the alveolus intact and interferes with surfactant function and alveolar epithelial integrity. It is canonical in the sense of being the model the field works from, not in the sense of being demonstrated; the vitamin_e_acetate_association_versus_causation discussion records what it still lacks.
Pathograph links
Inhalation of Vitamin E Acetate from Vaping Aerosol -> Disruption of Pulmonary Surfactant Function INDIRECT UNKNOWN INTERMEDIATES Inhaled vitamin E acetate reaches the alveolar surface where pulmonary surfactant operates. The steps between arrival and functional surfactant failure are not established in human disease, which is why this edge is typed as having unknown intermediates rather than being drawn as direct.
Disruption of Pulmonary Surfactant Function -> Acute Alveolar Inflammation and Diffuse Alveolar Damage INDIRECT UNKNOWN INTERMEDIATES Loss of surfactant function is proposed to leave the alveolus vulnerable to the acute injury seen on biopsy.
Thermal degradation of vitamin E acetate to ketene
ketene_thermal_degradation_route ALTERNATIVE
Evidence balance 2 support
A competing account in which the injurious agent is not vitamin E acetate itself but ketene, a highly toxic gas formed when the compound is heated in the device. It is not merely a rival: it is compatible with every piece of evidence supporting the canonical route, because a patient who inhales ketene has also inhaled vitamin E acetate, and lavage sampling would recover the parent compound either way. That is what makes the two hard to separate from human specimens, and why this entry curates the exposure node in terms of the compound inhaled rather than the species that does the damage.
Curated as a hypothesis rather than as pathophysiology nodes because no cited source demonstrates ketene in a patient. Adding a ketene node to the pathograph would assert a route that has been shown in a device, not in a lung.
Show evidence (2 references)
PMID:39078936 SUPPORT Other
"A potential mechanism for EVALI may involve VEA's thermal decomposition product, ketene, a highly poisonous gas, being generated under vaping conditions."
States the alternative mechanism as a mechanism, in the authors' own hedged terms. Tagged OTHER because the study is a device-chemistry experiment rather than clinical, in vitro or animal biology.
PMID:39078936 SUPPORT Other
"The production of ketene increased with repeat puffs and showed a correlation to temperatures (200 to 500 °C) measured within vaping devices."
Gives the condition under which the alternative route would operate, which is what makes it testable rather than merely available: ketene production rose with repeated puffs and tracked coil temperature across the range real devices reach.
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Discussions and Knowledge Gaps

1
Vitamin E acetate is recovered from the lungs of nearly every EVALI patient and from no comparator. Does it cause the disease, and is it the only thing that does?
KNOWLEDGE GAP OPEN vitamin_e_acetate_association_versus_causation
Attached to
pathophysiology#Inhalation of Vitamin E Acetate from Vaping Aerosol pathophysiology#Disruption of Pulmonary Surfactant Function
The exposure evidence here is unusually strong for an environmental disease: the agent was measured in the affected compartment, in 94% of cases and 0 of 99 comparators, with five rival toxicants assayed in the same fluid and essentially absent. It is much better than the correlational exposure data most entries in this knowledge base rest on. It is still an association, and the source paper says so. Its conclusion claims association in a convenience sample and does not claim causation, and the mouse study that followed opens by stating that additional studies are needed to establish whether a causal link exists. This entry follows both sources rather than rounding them up: the pathograph runs from the exposure to the injury, but the surfactant node is described as a proposal and the edges out of it are typed with unknown intermediates. Two specific gaps sit underneath. Nothing cited here demonstrates the surfactant lesion in human EVALI lung, so the mechanism connecting a recovered compound to an injured alveolus is inferred rather than observed. And 3 of 51 case patients had no detectable vitamin E acetate at all, which the single-agent account does not explain and which this entry does not explain away. National surveillance carries a second, independent version of the same problem: 2% of patients with product data reported using neither THC- nor nicotine-containing products at all, so the exposure route itself is unaccounted for in a small minority.
Proposed experiments
Measure surfactant function in human EVALI lung
surfactant_function_in_human_evali_lung
In bronchoalveolar lavage fluid from acute EVALI, measure surface tension and surfactant phospholipid composition directly, against both healthy vapers and patients with non-EVALI acute lung injury. The second comparator is the one that matters: a surfactant abnormality found in any acute lung injury would not support a vitamin E acetate-specific mechanism. Relate the measurements to the vitamin E acetate concentration in the same specimen, and include the case patients in whom none is detectable.
Show evidence (4 references)
PMID:31860793 SUPPORT Human Clinical
"Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States."
The source's own conclusion, and the reason this is a gap rather than a settled mechanism. It claims association in a convenience sample. PARTIAL because it supports the exposure-disease link while explicitly declining the causal claim this discussion is about.
PMID:32101656 SUPPORT Model Organism
"additional studies are necessary to determine whether a causal link exists between inhalation of vitamin E acetate and EVALI"
The authors of the follow-up animal study state the gap directly in their opening: additional studies are needed to determine whether a causal link exists. That a dedicated inhalation model was built on this premise is the clearest sign the question was open, not closed, after the human data landed.
PMID:31860793 SUPPORT Human Clinical
"Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group."
Also the source of the unexplained minority: 48 of 51 leaves three case patients with no detectable vitamin E acetate, which the discussion records rather than rounding to "all".
+ 1 more reference
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Pathophysiology

5
Inhalation of Vitamin E Acetate from Vaping Aerosol
Vitamin E acetate is used as a diluent or cutting agent in tetrahydrocannabinol-containing e-liquids sold outside regulated markets. Heating in a vaping device aerosolises it and delivers it to the distal airways, a route for which it was never assessed: the same compound is unremarkable when swallowed or applied to skin, so the exposure that matters here is specifically inhalational rather than the substance as such.
Intact vitamin E acetate disrupts alveolar surfactant
Animal models
Mouse inhaled vitamin E acetate model Mouse perturbs Delivers the implicated agent by the implicated route at a dose chosen to match human exposure, which is the arm of causation that human observational data cannot supply.
Downstream
Disruption of Pulmonary Surfactant Function Inhaled vitamin E acetate reaches the alveolar surface where pulmonary surfactant operates. The steps between arrival and functional surfactant failure are not established in human disease, which is why this edge is typed as having unknown intermediates rather than being drawn as direct. Intact vitamin E acetate disrupts alveolar surfactant
Alveolar Macrophage Lipid Accumulation Inhaled lipid is taken up by the alveolar macrophages that clear material from the airspace, which is the most directly observed consequence of the exposure in animal models.
Show evidence (3 references)
PMID:31860793 SUPPORT Human Clinical
"Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group."
The central exposure finding, and an unusually clean one: the agent was recovered from the lung compartment itself in 94% of cases and in none of 99 comparators, rather than being inferred from what patients reported buying.
PMID:31860793 SUPPORT Human Clinical
"No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each."
Narrows the exposure to this one compound. Five other candidate diluents and oils were assayed in the same fluid and were essentially absent, so the association is not a general finding of oils in the lungs of people who vape.
PMID:31860793 SUPPORT Human Clinical
"47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness."
Establishes the product route: vitamin E acetate reached these lungs through tetrahydrocannabinol-containing products, which is why this entry curates THC products as the vehicle rather than nicotine e-liquids.
Disruption of Pulmonary Surfactant Function
Vitamin E acetate is proposed to partition into the surfactant phospholipid film and disturb its packing, so the film can no longer lower alveolar surface tension normally. This entry curates the proposal as a proposal: no cited source here demonstrates the surfactant lesion in human EVALI lung.
Intact vitamin E acetate disrupts alveolar surfactant
alveolar type II cell CL:0002063 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves alveolar type II cell, annotated with pulmonary alveolar type 2 cell (CL:0002063). CL:0002063 is a cell type from the Cell Ontology.
surfactant homeostasis GO:0043129 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased surfactant homeostasis (GO:0043129). GO:0043129 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Acute Alveolar Inflammation and Diffuse Alveolar Damage Loss of surfactant function is proposed to leave the alveolus vulnerable to the acute injury seen on biopsy. Intact vitamin E acetate disrupts alveolar surfactant
Alveolar Macrophage Lipid Accumulation
Alveolar macrophages take up inhaled lipid and adopt a foamy, lipid-laden morphology. This is a marker of lipid exposure and not a diagnostic finding: lipid-laden macrophages appear in other conditions and their presence does not establish EVALI.
alveolar macrophage CL:0000583 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves alveolar macrophage (CL:0000583). CL:0000583 is a cell type from the Cell Ontology.
phagocytosis GO:0006909 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased phagocytosis (GO:0006909). GO:0006909 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Acute Alveolar Inflammation and Diffuse Alveolar Damage Lipid-laden macrophages accumulate within the same dense inflammatory infiltrate that defines the injury. Whether they drive that inflammation or merely mark it is not established, so this edge is typed with unknown intermediates.
Show evidence (2 references)
PMID:32822237 SUPPORT Model Organism
"We report that aerosolized vitamin E acetate (VEA) in mice causes dose-dependent pulmonary edema, an increase in alveolar-capillary barrier permeability to protein, and a bronchiolocentric pattern of inflammation with abundant lipid-laden and multinucleated macrophages."
A dose-dependent inhalation study reporting lipid-laden and multinucleated macrophages alongside pulmonary oedema and barrier permeability, which places this node inside the injury rather than beside it.
PMID:32822237 SUPPORT Model Organism
"In contrast, short-term exposure to aerosol generated from a JUUL device caused no detectable lung injury by lung water, BAL protein, or plasma SP-D after 15 days of exposure."
The control that makes the finding specific rather than a generic response to inhaled aerosol: a nicotine pod device aerosolised through the same apparatus produced no detectable lung injury by any of three measures.
Acute Alveolar Inflammation and Diffuse Alveolar Damage
The injured alveolus mounts an acute inflammatory response, with patterns of acute lung injury described on biopsy including diffuse alveolar damage, acute fibrinous pneumonitis and organising pneumonia.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
alveolus of lung UBERON:0002299 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in alveolus of lung (UBERON:0002299). UBERON:0002299 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Impaired Gas Exchange and Hypoxaemic Respiratory Failure Alveolar filling and inflammatory exudate obstruct gas exchange at the surface where it occurs.
Show evidence (2 references)
PMID:31860793 SUPPORT Human Clinical
"Histopathological features of acute lung injury have been described, including diffuse alveolar damage, acute fibrinous pneumonitis, and organizing pneumonia."
Names the acute lung injury patterns this node is built on, in the same words the node's description uses: diffuse alveolar damage, acute fibrinous pneumonitis and organising pneumonia.
PMID:32822237 SUPPORT In Vitro
"Furthermore, we found that VEA aerosol directly injures primary human type II alveolar epithelial cells, causing significant changes in gene expression and the secretion of inflammatory cytokines."
The human arm of the mechanism, and the only evidence in this entry from human cells: aerosolised vitamin E acetate directly injured primary human alveolar type II cells and drove cytokine secretion. It matters for this node because those are the surfactant-producing cells, so it connects the inflammatory injury to the surfactant proposal without asserting the surfactant lesion itself.
Impaired Gas Exchange and Hypoxaemic Respiratory Failure
Alveolar filling and loss of surfactant function impair gas exchange, producing hypoxaemia that in severe cases requires supplemental oxygen or mechanical ventilation.
lung UBERON:0002048 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lung (UBERON:0002048). UBERON:0002048 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported."
Quantifies how far this node goes in practice: in the founding cohort a quarter of patients required intubation and mechanical ventilation, which is the clinical expression of this node rather than a separate complication.
✶

Histopathology

1
Organising pneumonia with focal fibrosis
Where lung tissue was obtained, organising pneumonia has been described, consistent with the acute lung injury patterns reported in this disease. Biopsy is not required for diagnosis and is rarely performed, so this entry curates a single reported case rather than a series.
Show evidence (1 reference)
PMID:34584727 SUPPORT Human Clinical
"Lung biopsy revealed organizing pneumonia with focal fibrosis."
A single biopsied case, and curated as one. The strongest published pathology series on this disease could not be used here: PMID:31577870 cached with an empty body and so has no quotable text, which is why this section rests on a case report rather than on the series a curator would prefer.
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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for E-Cigarette or Vaping Product Use-Associated Lung Injury Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

12
Cardiovascular 1
Tachycardia HP:0001649 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tachycardia (HP:0001649). HP:0001649 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32320569 SUPPORT Human Clinical
"Among the hospitalized patients with fatal cases, 40 of 55 (73%) had hypoxia, 25 of 54 (46%) had tachycardia, and 26 of 52 (50%) had tachypnea at the time of admission to the hospital."
Both figures come from the FATAL-case subset of national surveillance, not from all patients, so they are curated as evidence that the sign occurs and explicitly NOT as a disease-wide frequency band: a proportion measured among those who died says nothing about those who did not.
Digestive 2
Nausea and vomiting HP:0002017 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Nausea and vomiting (HP:0002017). HP:0002017 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%)."
The cohort reports this only inside a category-level composite: respiratory symptoms 97%, gastrointestinal 77%, constitutional 100%. A composite figure cannot be assigned to a component phenotype, so it is curated here as evidence that the association exists and NOT as this phenotype's frequency band, which is deliberately left unset.
Diarrhea HP:0002014 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diarrhea (HP:0002014). HP:0002014 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%)."
The gastrointestinal category, reported at 77%, covers this phenotype. Curated as evidence that diarrhoea occurred, not as its frequency: the 77% is shared with nausea, vomiting and abdominal pain and cannot be apportioned between them from what is published.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%)."
The cohort reports this only inside a category-level composite: respiratory symptoms 97%, gastrointestinal 77%, constitutional 100%. A composite figure cannot be assigned to a component phenotype, so it is curated here as evidence that the association exists and NOT as this phenotype's frequency band, which is deliberately left unset.
Respiratory 6
Dyspnea HP:0002094 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dyspnea (HP:0002094). HP:0002094 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%)."
The cohort reports this only inside a category-level composite: respiratory symptoms 97%, gastrointestinal 77%, constitutional 100%. A composite figure cannot be assigned to a component phenotype, so it is curated here as evidence that the association exists and NOT as this phenotype's frequency band, which is deliberately left unset.
Cough HP:0012735 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cough (HP:0012735). HP:0012735 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%)."
The respiratory category, reported at 97%, covers this phenotype. Curated as evidence that cough occurred and not as its frequency: 97% is a figure for respiratory symptoms as a class, and dividing a class figure among its members is not something the source supports.
Hypoxemia HP:0012418 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hypoxemia (HP:0012418). HP:0012418 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported."
Supports hypoxaemia as the clinically dominant problem by way of what it required: 95% of patients were hospitalised and 26% intubated, which is a statement about oxygenation failure rather than about symptoms.
Tachypnea HP:0002789 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tachypnea (HP:0002789). HP:0002789 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32320569 SUPPORT Human Clinical
"Among the hospitalized patients with fatal cases, 40 of 55 (73%) had hypoxia, 25 of 54 (46%) had tachycardia, and 26 of 52 (50%) had tachypnea at the time of admission to the hospital."
Both figures come from the FATAL-case subset of national surveillance, not from all patients, so they are curated as evidence that the sign occurs and explicitly NOT as a disease-wide frequency band: a proportion measured among those who died says nothing about those who did not.
Respiratory failure HP:0002878 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory failure (HP:0002878). HP:0002878 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported."
Gives the proportion reaching this endpoint in the founding cohort: 26% intubated and mechanically ventilated, with two deaths among 98 patients.
Pulmonary infiltrates HP:0002113 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pulmonary infiltrates (HP:0002113). HP:0002113 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"All case patients had bilateral infiltrates on chest imaging."
Reads as a 100% frequency and must not be curated as one. The same paper's case definition REQUIRES pulmonary infiltrates on imaging, so a cohort assembled under it cannot contain a patient without them. The figure is circular with respect to frequency: it describes the case definition, not the biology, and this phenotype is therefore deliberately left unbanded.
Constitutional 1
Abdominal pain HP:0002027 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abdominal pain (HP:0002027). HP:0002027 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%)."
The gastrointestinal category, reported at 77%, covers this phenotype too. Curated as evidence of occurrence rather than frequency, for the same reason as the diarrhoea item above: the figure belongs to the category, not to any one symptom within it.
Other 1
Ground-glass opacification HP:0025179 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ground-glass opacification (HP:0025179). HP:0025179 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:31860793 SUPPORT Human Clinical
"such patients commonly are found to have basilar-predominant consolidation and ground-glass opacity."
States the imaging pattern and its distribution, with a caveat worth carrying: the same sentence notes radiographic findings may not be apparent on presentation, so a normal early film does not exclude the disease.
PMID:34584727 SUPPORT Human Clinical
"High-resolution computed tomography (HRCT) showed consolidation and ground-glass opacities in both lungs."
A worked single case showing the same pattern on high-resolution CT. Curated alongside the general statement above because it is the imaging description attached to the one biopsied case this entry cites.
💊

Medical Actions

3
Vaping Cessation Counselling
Action: behavioral counselingNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is behavioral counseling (NCIT:C181743). NCIT:C181743 is a clinical intervention from the NCI Thesaurus. Ontology label: Behavioral Counseling NCIT:C181743
Stopping the exposure is the only intervention that addresses the cause rather than the injury, and it is what separates recovery from relapse: this entry's progression section records that resuming vaping is a route back into the disease. Curated without efficacy evidence, because none of the cited sources tests counselling as an intervention.
Mechanism Target:
INHIBITS Inhalation of Vitamin E Acetate from Vaping Aerosol — Acts on the initiating node by removing the exposure, which is the only point in this pathograph where the disease can be prevented rather than treated.
Supplemental Oxygen and Mechanical Ventilation
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
Oxygen, and mechanical ventilation where needed, is the treatment that addresses the gas-exchange failure directly. It is supportive rather than disease-modifying: it substitutes for the failing alveolus while the injury resolves. Named for the two interventions rather than for supportive care in general, so that the DEVICE modality describes what is actually delivered.
Mechanism Target:
BYPASSES Impaired Gas Exchange and Hypoxaemic Respiratory Failure — Does not act on the injury at all. It substitutes for the function the injured alveolus has lost, which is what BYPASSES means here and is the honest distinction from the glucocorticoid entry below, which does target a mechanism.
Show evidence (1 reference)
PMID:31860793 SUPPORT Human Clinical
"Nearly half the patients (47%) required intensive care to treat respiratory failure."
Quantifies the need for this treatment rather than its efficacy: nearly half of patients required intensive care for respiratory failure, which is the clinical demand this entry curates the treatment against.
Systemic Glucocorticoid Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: systemic glucocorticoid CHEBI:24261 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses systemic glucocorticoid, annotated with glucocorticoid (CHEBI:24261). CHEBI:24261 is a therapeutic agent from Chemical Entities of Biological Interest.
Systemic corticosteroids are the mainstay of treatment, given alongside oxygen and supportive care. The evidence is observational: patients improved on treatment in uncontrolled cohorts, and no controlled trial exists, so response cannot be separated from removal of the exposure and the natural course of an acute injury.
Mechanism Target:
INHIBITS Acute Alveolar Inflammation and Diffuse Alveolar Damage — The rationale is suppression of the acute alveolar inflammatory response, which is the node this entry curates as producing the gas-exchange failure.
Show evidence (1 reference)
PMID:32320538 SUPPORT Human Clinical
"Patients had dramatic improvement with systemic glucocorticoid therapy and 14/15 were discharged on room air."
The observational basis for corticosteroid use, quoted with the qualifier it carries: 15 adolescents, no control arm, and "dramatic improvement" is the authors' characterisation of an uncontrolled series. It supports the practice without establishing efficacy.
🌍

Environmental Factors

1
Use of tetrahydrocannabinol-containing vaping products from informal sources
No `exposure_term` is bound. ECTO was searched for "vaping", "electronic cigarette" and "cigarette"; the only candidate returned is ECTO:0100003 "exposure to cigarette smoking", which is a different exposure entirely - combusted tobacco rather than a heated e-liquid aerosol - and binding it would assert the wrong thing in a machine-readable field. This is the second ontology gap in this entry, alongside the absent MONDO term, and both are recorded rather than filled with an approximate term.
Vaping THC-containing e-liquid, typically obtained from informal or illicit sellers rather than a regulated market, is the exposure route that carried vitamin E acetate into the lung during the outbreak.
Show evidence (2 references)
PMID:31491072 SUPPORT Human Clinical
"A total of 89% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported."
Establishes THC-containing products as the dominant exposure route in the founding cohort, while noting the heterogeneity of products and devices that makes a single culprit product impossible to name.
PMID:31671085 SUPPORT Human Clinical
"86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both."
The national product-use breakdown behind this exposure entry, and the reason it is named for THC-containing products: 86% reported them, against 64% for nicotine-containing products, with half the patients reporting both.
Mechanism Target:
TRIGGERS Inhalation of Vitamin E Acetate from Vaping Aerosol — Using these products is the act by which vitamin E acetate is aerosolised and inhaled, which is the initiating step of this entry's pathograph.
Show evidence (1 reference)
PMID:31860793 SUPPORT Human Clinical
"Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group."
Links the exposure to the mechanism at the point where it can be checked: the compound was recovered from the lungs of people who used these products and from none of the comparators.
🔬

Biochemical Markers

1
Peripheral white cell count and differential
Show evidence (1 reference)
PMID:32320569 SUPPORT Human Clinical
"The laboratory values at the initial admission showed that 37 of 52 patients (71%) with fatal cases had leukocytosis (white-cell counts >11,000 per cubic millimeter) and 29 of 45 (64%) had neutrophil predominance (white-cell count with >80% neutrophils)."
Gives both the thresholds used and the proportions meeting them. The denominators matter and are stated: 52 and 45 patients with FATAL cases, so this describes the laboratory picture of the severe end of the disease. It is curated as a finding, not as a frequency for the disease as a whole.
🔬

Diagnosis

2
Chest imaging for bilateral pulmonary opacities
Chest imaging is the one positive limb of the case definition. It establishes bilateral pulmonary opacities and shows the characteristic ground-glass pattern, but it does not distinguish this disease from the infections the definition requires be excluded.
chest computed tomography NCIT:C191501 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:31860793 SUPPORT Human Clinical
"Radio-graphic findings may not be apparent on presentation, but such patients commonly are found to have basilar-predominant consolidation and ground-glass opacity."
States both what imaging shows and its limit as a diagnostic test, and the quote spans both clauses because the limit is the load-bearing half here: a normal early study does not exclude the disease, so imaging cannot rule it out at presentation, which matters for a diagnosis that is otherwise one of exclusion. The source's line-break artefact in "Radio-graphic" is quoted as printed rather than silently repaired.
Exclusion of pulmonary infection
The load-bearing limb of the diagnosis, and the one with no positive test behind it. Because the case definition requires that the illness not be attributable to another cause, the diagnosis is only as good as the search for alternatives, and its performance therefore varies with how thoroughly infection was ruled out rather than with any property of the disease.
Show evidence (1 reference)
PMID:31491072 SUPPORT Human Clinical
"We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes."
The case definition in the authors' own words. Its third limb, that illnesses were "not attributed to other causes", is what makes this a diagnosis of exclusion and is why the infection workup is modelled here as a diagnostic step rather than as background.
📈

Progression

2
Relapse on re-exposure
Resuming vaping is a route back into the disease, which is why cessation is curated as a treatment rather than as advice. No cited source here quantifies the relapse rate, so this phase is recorded as a course without a frequency.
Recovery and residual impairment
Symptoms resolve in most survivors, but resolution of symptoms does not mean resolution of injury: the majority of a followed-up adolescent cohort had abnormal pulmonary function tests despite reporting they felt better.
Show evidence (1 reference)
PMID:32320538 SUPPORT Human Clinical
"Despite 11/11 patients reporting resolved or improved symptoms, 7/11 had abnormalities on pulmonary function testing."
The dissociation between how patients feel and what their lungs do, which is the reason this entry curates a residual-impairment phase at all. 7 of 11 had abnormal pulmonary function testing while 11 of 11 reported resolved or improved symptoms, so a symptom-based follow-up would have recorded full recovery.
📊

Prevalence

1
United States, national outbreak reporting to the CDC
Cases In Literature Unknown
A cumulative outbreak case count reported to a national surveillance system, not a population rate: no denominator is given and none is derived here. The count is also a floor rather than an estimate, since it counts only cases that were recognised as EVALI and reported.
Show evidence (1 reference)
PMID:32320569 SUPPORT Human Clinical
"As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC)."
Gives the cumulative national burden at a stated date, which is the form the epidemiology of an outbreak takes.
⚖️

Clinical Burden

High
An acute illness that hospitalised the large majority of those it affected, put a quarter of the founding cohort on mechanical ventilation, and killed dozens nationally within months. The burden also falls unevenly with age in a way worth recording: older patients were a minority of non-fatal cases but a majority of fatal ones, so the same disease carries a different burden at 50 than at 20.
Show evidence (2 references)
PMID:31671085 SUPPORT Human Clinical
"The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years."
Independent corroboration of the age contrast from a different surveillance report and a different cut of the data: median age 23 among survivors against 45 among those who died. Two sources reporting the same direction by different measures is why this is curated as a real feature of the disease rather than a single cohort's artefact.
PMID:32320569 SUPPORT Human Clinical
"The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%])."
Older patients were a minority of non-fatal cases (22% aged 35 or over) but a majority of fatal ones (73%), so age is not merely associated with death but distributed in opposite directions across the two groups. Curated as an observed contrast in national surveillance data, not as a validated prognostic rule.
🐁

Animal Models

1
Mouse inhaled vitamin E acetate model
Mice exposed to aerosolised vitamin E acetate at doses scaled to human vaping, compared against a propylene glycol/vegetable glycerin vehicle and against air.
Species
Mouse
Publication
PMID:32101656
Pathograph links
Inhalation of Vitamin E Acetate from Vaping Aerosol perturbs fidelity: moderate Delivers the implicated agent by the implicated route at a dose chosen to match human exposure, which is the arm of causation that human observational data cannot supply.
Limitations: A mouse airway is not a human airway, the exposure ran two weeks rather than the months-to-years of real use, and the model tests vitamin E acetate alone rather than the heterogeneous mixtures people actually vaped.
Show evidence (1 reference)
PMID:32101656 SUPPORT Model Organism
"We exposed 30 mice (in three groups of 10) to aerosols generated from vitamin E acetate, a mixture of propylene glycol and vegetable glycerin (PG–VG), or air (controls)."
Describes the exposure design, including the two comparator arms that make the vitamin E acetate arm interpretable.
Show evidence (1 reference)
PMID:32822237 SUPPORT Model Organism
"We report that aerosolized vitamin E acetate (VEA) in mice causes dose-dependent pulmonary edema, an increase in alveolar-capillary barrier permeability to protein, and a bronchiolocentric pattern of inflammation with abundant lipid-laden and multinucleated macrophages."
Attests that inhalational vitamin E acetate models are informative for this disease at all, which is a different claim from any single mechanism link: a dose-dependent response reproducing oedema, barrier permeability and lipid-laden macrophages is what makes the system worth using.
{ }

Source YAML

click to show 
name: E-Cigarette or Vaping Product Use-Associated Lung Injury
creation_date: "2026-08-23T22:55:00Z"
category: Environmental
categories:
- Toxic Exposure Disorder
- Occupational and Environmental Lung Disease
- Environmental Health Disorder
synonyms:
- EVALI
- e-cigarette or vaping product use-associated lung injury
- vaping-associated pulmonary illness
- vaping-related disorder
description: >-
  An acute inhalational lung injury caused by use of e-cigarette or vaping
  products, recognised as a distinct entity during a 2019 outbreak in the United
  States. Most cases were associated with vaping tetrahydrocannabinol-containing
  products obtained from informal sources, and vitamin E acetate used as a
  diluent in those products is the agent most strongly implicated. Patients
  present with respiratory, gastrointestinal and constitutional symptoms
  together, with bilateral pulmonary opacities on imaging and no identified
  infection.
notes: >-
  This entry has no `disease_term`. MONDO records no term for this disease: a
  full-text search of MONDO for "vaping", "e-cigarette" and "EVALI" returns
  nothing, so there is no identifier to bind rather than a specific one that was
  overlooked. The disease is not unidentified, only un-MONDO-ed: ICD-10-CM codes
  it as U07.0 "Vaping-related disorder", and that code is bound under `mappings`
  instead. A curator who later finds a MONDO term should add `disease_term` and
  leave the ICD-10-CM mapping in place.

  One feature that belongs in this entry is absent for want of a quotable source
  rather than by judgement: weight loss, part of the constitutional cluster, is
  described in none of the references cached here. It is waiting on a source, not
  on effort. The same applies to the pathology series PMID:31577870, which cached
  with an empty body and so could not support the histopathology section.

  Oxidative stress is deliberately NOT curated as a pathophysiology node. It was
  proposed on the strength of PMID:32822237, but that paper does not show it: the
  only occurrence of "oxidat" in its full text describes vitamin E's normal
  ANTIOXIDANT function, scavenging free radicals and terminating lipid
  peroxidation. The paper is used here for what it does show, which is direct
  toxicity to human alveolar type II cells and dose-dependent murine lung injury.
  A node asserting oxidative injury would need a source that reports it.

  An earlier version of this note also claimed ground-glass opacification was
  unsupportable. That was wrong, and wrong in an instructive way: a dedicated
  imaging paper was searched for and not found, and the absence of a NEW source
  was mistaken for the absence of ANY source, when two references already cached
  for this entry state the finding plainly. The phenotype is curated below. A
  claim that something cannot be sourced should be checked against what is
  already on disk before it is written down.
mappings:
  icd10cm_mappings:
  - term:
      id: ICD10CM:U07.0
      label: Vaping-related disorder
    mapping_predicate: skos:exactMatch
    mapping_justification: semapv:ManualMappingCuration
    notes: >-
      The code created for this disease during the outbreak, and the closest
      thing it has to a primary identifier in any coding system this repository
      binds.
pathophysiology:
- name: Inhalation of Vitamin E Acetate from Vaping Aerosol
  biological_scale: ORGANISM
  description: >-
    Vitamin E acetate is used as a diluent or cutting agent in
    tetrahydrocannabinol-containing e-liquids sold outside regulated markets.
    Heating in a vaping device aerosolises it and delivers it to the distal
    airways, a route for which it was never assessed: the same compound is
    unremarkable when swallowed or applied to skin, so the exposure that matters
    here is specifically inhalational rather than the substance as such.
  chemical_entities:
  - preferred_term: vitamin E acetate
    term:
      id: CHEBI:32321
      label: alpha-Tocopherol acetate
  - preferred_term: tetrahydrocannabinol
    term:
      id: CHEBI:66964
      label: Delta(9)-tetrahydrocannabinol
  evidence:
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group.
    explanation: >-
      The central exposure finding, and an unusually clean one: the agent was
      recovered from the lung compartment itself in 94% of cases and in none of 99
      comparators, rather than being inferred from what patients reported buying.
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each.
    explanation: >-
      Narrows the exposure to this one compound. Five other candidate diluents and
      oils were assayed in the same fluid and were essentially absent, so the
      association is not a general finding of oils in the lungs of people who vape.
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness.
    explanation: >-
      Establishes the product route: vitamin E acetate reached these lungs through
      tetrahydrocannabinol-containing products, which is why this entry curates THC
      products as the vehicle rather than nicotine e-liquids.
  downstream:
  - target: Disruption of Pulmonary Surfactant Function
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - vea_surfactant_route
    description: >-
      Inhaled vitamin E acetate reaches the alveolar surface where pulmonary
      surfactant operates. The steps between arrival and functional surfactant
      failure are not established in human disease, which is why this edge is
      typed as having unknown intermediates rather than being drawn as direct.
  - target: Alveolar Macrophage Lipid Accumulation
    causal_link_type: DIRECT
    description: >-
      Inhaled lipid is taken up by the alveolar macrophages that clear material
      from the airspace, which is the most directly observed consequence of the
      exposure in animal models.
    evidence:
    - reference: PMID:32101656
      reference_title: "An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Cells isolated from the BAL fluid of vitamin E acetate–exposed mice contained numerous lipid-laden macrophages
      explanation: >-
        Establishes the edge in the only system where the exposure can be controlled:
        mice exposed to aerosolised vitamin E acetate had numerous lipid-laden
        macrophages in lavage fluid, which the authors note matches what is seen
        clinically.
- name: Disruption of Pulmonary Surfactant Function
  biological_scale: MOLECULAR
  description: >-
    Vitamin E acetate is proposed to partition into the surfactant phospholipid
    film and disturb its packing, so the film can no longer lower alveolar
    surface tension normally. This entry curates the proposal as a proposal: no
    cited source here demonstrates the surfactant lesion in human EVALI lung.
  biological_processes:
  - preferred_term: surfactant homeostasis
    term:
      id: GO:0043129
      label: surfactant homeostasis
    modifier: DECREASED
  cell_types:
  - preferred_term: alveolar type II cell
    term:
      id: CL:0002063
      label: pulmonary alveolar type 2 cell
  downstream:
  - target: Acute Alveolar Inflammation and Diffuse Alveolar Damage
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - vea_surfactant_route
    description: >-
      Loss of surfactant function is proposed to leave the alveolus vulnerable to
      the acute injury seen on biopsy.
- name: Alveolar Macrophage Lipid Accumulation
  biological_scale: CELLULAR
  description: >-
    Alveolar macrophages take up inhaled lipid and adopt a foamy, lipid-laden
    morphology. This is a marker of lipid exposure and not a diagnostic finding:
    lipid-laden macrophages appear in other conditions and their presence does
    not establish EVALI.
  cell_types:
  - preferred_term: alveolar macrophage
    term:
      id: CL:0000583
      label: alveolar macrophage
  biological_processes:
  - preferred_term: phagocytosis
    term:
      id: GO:0006909
      label: phagocytosis
    modifier: INCREASED
  evidence:
  - reference: PMID:32822237
    reference_title: "Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      We report that aerosolized vitamin E acetate (VEA) in mice causes dose-dependent pulmonary edema, an increase in alveolar-capillary barrier permeability to protein, and a bronchiolocentric pattern of inflammation with abundant lipid-laden and multinucleated macrophages.
    explanation: >-
      A dose-dependent inhalation study reporting lipid-laden and multinucleated
      macrophages alongside pulmonary oedema and barrier permeability, which places
      this node inside the injury rather than beside it.
  - reference: PMID:32822237
    reference_title: "Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      In contrast, short-term exposure to aerosol generated from a JUUL device caused no detectable lung injury by lung water, BAL protein, or plasma SP-D after 15 days of exposure.
    explanation: >-
      The control that makes the finding specific rather than a generic response to
      inhaled aerosol: a nicotine pod device aerosolised through the same apparatus
      produced no detectable lung injury by any of three measures.
  downstream:
  - target: Acute Alveolar Inflammation and Diffuse Alveolar Damage
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Lipid-laden macrophages accumulate within the same dense inflammatory
      infiltrate that defines the injury. Whether they drive that inflammation or
      merely mark it is not established, so this edge is typed with unknown
      intermediates.
- name: Acute Alveolar Inflammation and Diffuse Alveolar Damage
  biological_scale: TISSUE
  description: >-
    The injured alveolus mounts an acute inflammatory response, with patterns of
    acute lung injury described on biopsy including diffuse alveolar damage,
    acute fibrinous pneumonitis and organising pneumonia.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  locations:
  - preferred_term: alveolus of lung
    term:
      id: UBERON:0002299
      label: alveolus of lung
  evidence:
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Histopathological features of acute lung injury have been described, including diffuse alveolar damage, acute fibrinous pneumonitis, and organizing pneumonia.
    explanation: >-
      Names the acute lung injury patterns this node is built on, in the same words
      the node's description uses: diffuse alveolar damage, acute fibrinous
      pneumonitis and organising pneumonia.
  - reference: PMID:32822237
    reference_title: "Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Furthermore, we found that VEA aerosol directly injures primary human type II alveolar epithelial cells, causing significant changes in gene expression and the secretion of inflammatory cytokines.
    explanation: >-
      The human arm of the mechanism, and the only evidence in this entry from human
      cells: aerosolised vitamin E acetate directly injured primary human alveolar
      type II cells and drove cytokine secretion. It matters for this node because
      those are the surfactant-producing cells, so it connects the inflammatory
      injury to the surfactant proposal without asserting the surfactant lesion
      itself.
  downstream:
  - target: Impaired Gas Exchange and Hypoxaemic Respiratory Failure
    causal_link_type: DIRECT
    description: >-
      Alveolar filling and inflammatory exudate obstruct gas exchange at the
      surface where it occurs.
- name: Impaired Gas Exchange and Hypoxaemic Respiratory Failure
  biological_scale: ORGANISM
  description: >-
    Alveolar filling and loss of surfactant function impair gas exchange,
    producing hypoxaemia that in severe cases requires supplemental oxygen or
    mechanical ventilation.
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported.
    explanation: >-
      Quantifies how far this node goes in practice: in the founding cohort a quarter
      of patients required intubation and mechanical ventilation, which is the
      clinical expression of this node rather than a separate complication.
mechanistic_hypotheses:
- hypothesis_group_id: vea_surfactant_route
  hypothesis_label: Intact vitamin E acetate disrupts alveolar surfactant
  status: CANONICAL
  description: >-
    The default model this entry's pathograph is drawn against: inhaled vitamin E
    acetate reaches the alveolus intact and interferes with surfactant function
    and alveolar epithelial integrity. It is canonical in the sense of being the
    model the field works from, not in the sense of being demonstrated; the
    vitamin_e_acetate_association_versus_causation discussion records what it
    still lacks.
- hypothesis_group_id: ketene_thermal_degradation_route
  hypothesis_label: Thermal degradation of vitamin E acetate to ketene
  status: ALTERNATIVE
  description: >-
    A competing account in which the injurious agent is not vitamin E acetate
    itself but ketene, a highly toxic gas formed when the compound is heated in
    the device. It is not merely a rival: it is compatible with every piece of
    evidence supporting the canonical route, because a patient who inhales
    ketene has also inhaled vitamin E acetate, and lavage sampling would recover
    the parent compound either way. That is what makes the two hard to separate
    from human specimens, and why this entry curates the exposure node in terms
    of the compound inhaled rather than the species that does the damage.
  evidence:
  - reference: PMID:39078936
    reference_title: "Conditions Leading to Ketene Formation in Vaping Devices and Implications for Public Health."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      A potential mechanism for EVALI may involve VEA's thermal decomposition product, ketene, a highly poisonous gas, being generated under vaping conditions.
    explanation: >-
      States the alternative mechanism as a mechanism, in the authors' own
      hedged terms. Tagged OTHER because the study is a device-chemistry
      experiment rather than clinical, in vitro or animal biology.
  - reference: PMID:39078936
    reference_title: "Conditions Leading to Ketene Formation in Vaping Devices and Implications for Public Health."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The production of ketene increased with repeat puffs and showed a correlation to temperatures (200 to 500 °C) measured within vaping devices.
    explanation: >-
      Gives the condition under which the alternative route would operate, which
      is what makes it testable rather than merely available: ketene production
      rose with repeated puffs and tracked coil temperature across the range
      real devices reach.
  notes: >-
    Curated as a hypothesis rather than as pathophysiology nodes because no
    cited source demonstrates ketene in a patient. Adding a ketene node to the
    pathograph would assert a route that has been shown in a device, not in a
    lung.
phenotypes:
- category: Respiratory
  name: Dyspnea
  description: >-
    Breathlessness, typically progressive over days to weeks before presentation.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%).
    explanation: >-
      The cohort reports this only inside a category-level composite: respiratory
      symptoms 97%, gastrointestinal 77%, constitutional 100%. A composite figure
      cannot be assigned to a component phenotype, so it is curated here as evidence
      that the association exists and NOT as this phenotype's frequency band, which is
      deliberately left unset.
- category: Respiratory
  name: Cough
  description: >-
    Usually non-productive, and part of the respiratory symptom cluster that
    dominates presentation.
  phenotype_term:
    preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%).
    explanation: >-
      The respiratory category, reported at 97%, covers this phenotype. Curated as
      evidence that cough occurred and not as its frequency: 97% is a figure for
      respiratory symptoms as a class, and dividing a class figure among its
      members is not something the source supports.
- category: Gastrointestinal
  name: Nausea and vomiting
  description: >-
    Gastrointestinal symptoms are prominent and often accompany or precede the
    respiratory complaints. That combination is the feature that most distinguishes
    this presentation from ordinary community-acquired pneumonia, in which
    prominent vomiting and diarrhoea would be unusual.
  phenotype_term:
    preferred_term: Nausea and vomiting
    term:
      id: HP:0002017
      label: Nausea and vomiting
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%).
    explanation: >-
      The cohort reports this only inside a category-level composite: respiratory
      symptoms 97%, gastrointestinal 77%, constitutional 100%. A composite figure
      cannot be assigned to a component phenotype, so it is curated here as evidence
      that the association exists and NOT as this phenotype's frequency band, which is
      deliberately left unset.
- category: Gastrointestinal
  name: Diarrhea
  description: >-
    Part of the gastrointestinal cluster reported alongside nausea, vomiting and
    abdominal pain.
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%).
    explanation: >-
      The gastrointestinal category, reported at 77%, covers this phenotype.
      Curated as evidence that diarrhoea occurred, not as its frequency: the 77%
      is shared with nausea, vomiting and abdominal pain and cannot be
      apportioned between them from what is published.
- category: Gastrointestinal
  name: Abdominal pain
  description: >-
    Reported within the same gastrointestinal cluster.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%).
    explanation: >-
      The gastrointestinal category, reported at 77%, covers this phenotype too.
      Curated as evidence of occurrence rather than frequency, for the same reason
      as the diarrhoea item above: the figure belongs to the category, not to any
      one symptom within it.
- category: Constitutional
  name: Fever
  description: >-
    Subjective or documented fever with chills and malaise, within the
    constitutional cluster that was near-universal in the founding cohort.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%).
    explanation: >-
      The cohort reports this only inside a category-level composite: respiratory
      symptoms 97%, gastrointestinal 77%, constitutional 100%. A composite figure
      cannot be assigned to a component phenotype, so it is curated here as evidence
      that the association exists and NOT as this phenotype's frequency band, which is
      deliberately left unset.
- category: Respiratory
  name: Hypoxemia
  description: >-
    Reduced oxygen saturation, frequently the reason for admission and the
    physiological expression of the gas-exchange node.
  phenotype_term:
    preferred_term: Hypoxemia
    term:
      id: HP:0012418
      label: Hypoxemia
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported.
    explanation: >-
      Supports hypoxaemia as the clinically dominant problem by way of what it
      required: 95% of patients were hospitalised and 26% intubated, which is a
      statement about oxygenation failure rather than about symptoms.
- category: Cardiovascular
  name: Tachycardia
  description: >-
    Raised heart rate at presentation, recorded in roughly half of hospitalised
    patients in the fatal-case series.
  phenotype_term:
    preferred_term: Tachycardia
    term:
      id: HP:0001649
      label: Tachycardia
  evidence:
  - reference: PMID:32320569
    reference_title: "Hospitalizations and Deaths Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Among the hospitalized patients with fatal cases, 40 of 55 (73%) had hypoxia, 25 of 54 (46%) had tachycardia, and 26 of 52 (50%) had tachypnea at the time of admission to the hospital.
    explanation: >-
      Both figures come from the FATAL-case subset of national surveillance, not from
      all patients, so they are curated as evidence that the sign occurs and
      explicitly NOT as a disease-wide frequency band: a proportion measured among
      those who died says nothing about those who did not.
- category: Respiratory
  name: Tachypnea
  description: >-
    Raised respiratory rate at presentation, recorded alongside tachycardia and
    hypoxia in the same admission vitals.
  phenotype_term:
    preferred_term: Tachypnea
    term:
      id: HP:0002789
      label: Tachypnea
  evidence:
  - reference: PMID:32320569
    reference_title: "Hospitalizations and Deaths Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Among the hospitalized patients with fatal cases, 40 of 55 (73%) had hypoxia, 25 of 54 (46%) had tachycardia, and 26 of 52 (50%) had tachypnea at the time of admission to the hospital.
    explanation: >-
      Both figures come from the FATAL-case subset of national surveillance, not from
      all patients, so they are curated as evidence that the sign occurs and
      explicitly NOT as a disease-wide frequency band: a proportion measured among
      those who died says nothing about those who did not.
- category: Respiratory
  name: Respiratory failure
  description: >-
    The severe end of the disease, requiring intubation and mechanical ventilation
    in a substantial minority.
  phenotype_term:
    preferred_term: Respiratory failure
    term:
      id: HP:0002878
      label: Respiratory failure
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported.
    explanation: >-
      Gives the proportion reaching this endpoint in the founding cohort: 26%
      intubated and mechanically ventilated, with two deaths among 98 patients.
- category: Imaging
  name: Ground-glass opacification
  description: >-
    The characteristic chest CT pattern, typically bilateral and
    basilar-predominant, accompanying consolidation. No frequency is curated: the
    cited sources describe the pattern qualitatively as a common finding without
    giving a denominator this entry can quote.
  phenotype_term:
    preferred_term: Ground-glass opacification
    term:
      id: HP:0025179
      label: Ground-glass opacification
  evidence:
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      such patients commonly are found to have basilar-predominant consolidation and ground-glass opacity.
    explanation: >-
      States the imaging pattern and its distribution, with a caveat worth carrying:
      the same sentence notes radiographic findings may not be apparent on
      presentation, so a normal early film does not exclude the disease.
  - reference: PMID:34584727
    reference_title: "Treatment of electronic cigarette or vaping product use-associated lung injury (EVALI) by corticosteroid and low-dose pirfenidone: Report of a case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      High-resolution computed tomography (HRCT) showed consolidation and ground-glass opacities in both lungs.
    explanation: >-
      A worked single case showing the same pattern on high-resolution CT. Curated
      alongside the general statement above because it is the imaging description
      attached to the one biopsied case this entry cites.
- category: Imaging
  name: Pulmonary infiltrates
  description: >-
    Bilateral pulmonary infiltrates are present by definition rather than by
    observation, and the distinction matters for anyone reading a frequency from
    this entry.
  phenotype_term:
    preferred_term: Pulmonary infiltrates
    term:
      id: HP:0002113
      label: Pulmonary infiltrates
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All case patients had bilateral infiltrates on chest imaging.
    explanation: >-
      Reads as a 100% frequency and must not be curated as one. The same paper's case
      definition REQUIRES pulmonary infiltrates on imaging, so a cohort assembled
      under it cannot contain a patient without them. The figure is circular with
      respect to frequency: it describes the case definition, not the biology, and
      this phenotype is therefore deliberately left unbanded.
definitions:
- name: Outbreak surveillance case definition
  definition_type: CASE_DEFINITION
  derivation_basis: ESTABLISHED_CRITERIA
  description: >-
    Three conjoined criteria: vaping exposure within 90 days, pulmonary
    infiltrates on imaging, and exclusion of alternative causes. It is a
    definition of exclusion built around an exposure history, with no confirmatory
    test, which is why the diagnosis depends on asking about vaping at all.
  validation_status:
    status: UNVALIDATED
    rationale: >-
      Adopted for outbreak surveillance rather than validated against a gold
      standard, since no independent reference standard for the disease exists.
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes.
    explanation: >-
      States the operative case definition in the authors' own words. Its third limb
      does the most work and is the least visible: illnesses "not attributed to other
      causes" makes this a diagnosis of exclusion, so its performance depends on how
      hard alternatives were sought.
diagnosis:
- name: Chest imaging for bilateral pulmonary opacities
  diagnosis_term:
    preferred_term: chest computed tomography
    term:
      id: NCIT:C191501
      label: Chest Computed Tomography
  description: >-
    Chest imaging is the one positive limb of the case definition. It
    establishes bilateral pulmonary opacities and shows the characteristic
    ground-glass pattern, but it does not distinguish this disease from the
    infections the definition requires be excluded.
  evidence:
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Radio-graphic findings may not be apparent on presentation, but such patients commonly are found to have basilar-predominant consolidation and ground-glass opacity.
    explanation: >-
      States both what imaging shows and its limit as a diagnostic test, and the
      quote spans both clauses because the limit is the load-bearing half here: a
      normal early study does not exclude the disease, so imaging cannot rule it
      out at presentation, which matters for a diagnosis that is otherwise one of
      exclusion. The source's line-break artefact in "Radio-graphic" is quoted as
      printed rather than silently repaired.
- name: Exclusion of pulmonary infection
  description: >-
    The load-bearing limb of the diagnosis, and the one with no positive test
    behind it. Because the case definition requires that the illness not be
    attributable to another cause, the diagnosis is only as good as the search
    for alternatives, and its performance therefore varies with how thoroughly
    infection was ruled out rather than with any property of the disease.
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes.
    explanation: >-
      The case definition in the authors' own words. Its third limb, that illnesses
      were "not attributed to other causes", is what makes this a diagnosis of
      exclusion and is why the infection workup is modelled here as a diagnostic step
      rather than as background.
environmental:
- name: Use of tetrahydrocannabinol-containing vaping products from informal sources
  description: >-
    Vaping THC-containing e-liquid, typically obtained from informal or illicit
    sellers rather than a regulated market, is the exposure route that carried
    vitamin E acetate into the lung during the outbreak.
  notes: >-
    No `exposure_term` is bound. ECTO was searched for "vaping", "electronic
    cigarette" and "cigarette"; the only candidate returned is
    ECTO:0100003 "exposure to cigarette smoking", which is a different exposure
    entirely - combusted tobacco rather than a heated e-liquid aerosol - and
    binding it would assert the wrong thing in a machine-readable field. This is
    the second ontology gap in this entry, alongside the absent MONDO term, and
    both are recorded rather than filled with an approximate term.
  evidence:
  - reference: PMID:31491072
    reference_title: "Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A total of 89% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported.
    explanation: >-
      Establishes THC-containing products as the dominant exposure route in the
      founding cohort, while noting the heterogeneity of products and devices that
      makes a single culprit product impossible to name.
  - reference: PMID:31671085
    reference_title: "Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both.
    explanation: >-
      The national product-use breakdown behind this exposure entry, and the reason it
      is named for THC-containing products: 86% reported them, against 64% for
      nicotine-containing products, with half the patients reporting both.
  influences_mechanisms:
  - target: Inhalation of Vitamin E Acetate from Vaping Aerosol
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Using these products is the act by which vitamin E acetate is aerosolised
      and inhaled, which is the initiating step of this entry's pathograph.
    evidence:
    - reference: PMID:31860793
      reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group.
      explanation: >-
        Links the exposure to the mechanism at the point where it can be checked: the
        compound was recovered from the lungs of people who used these products and
        from none of the comparators.
animal_models:
- name: Mouse inhaled vitamin E acetate model
  species: Mouse
  publication: PMID:32101656
  description: >-
    Mice exposed to aerosolised vitamin E acetate at doses scaled to human
    vaping, compared against a propylene glycol/vegetable glycerin vehicle and
    against air.
  evidence:
  - reference: PMID:32822237
    reference_title: "Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      We report that aerosolized vitamin E acetate (VEA) in mice causes dose-dependent pulmonary edema, an increase in alveolar-capillary barrier permeability to protein, and a bronchiolocentric pattern of inflammation with abundant lipid-laden and multinucleated macrophages.
    explanation: >-
      Attests that inhalational vitamin E acetate models are informative for this
      disease at all, which is a different claim from any single mechanism link: a
      dose-dependent response reproducing oedema, barrier permeability and
      lipid-laden macrophages is what makes the system worth using.
  modeled_mechanisms:
  - target: Inhalation of Vitamin E Acetate from Vaping Aerosol
    relationship: PERTURBS
    fidelity: MODERATE
    description: >-
      Delivers the implicated agent by the implicated route at a dose chosen to
      match human exposure, which is the arm of causation that human
      observational data cannot supply.
    limitations: >-
      A mouse airway is not a human airway, the exposure ran two weeks rather
      than the months-to-years of real use, and the model tests vitamin E acetate
      alone rather than the heterogeneous mixtures people actually vaped.
    evidence:
    - reference: PMID:32101656
      reference_title: "An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        We exposed 30 mice (in three groups of 10) to aerosols generated from vitamin E acetate, a mixture of propylene glycol and vegetable glycerin (PG–VG), or air (controls).
      explanation: >-
        Describes the exposure design, including the two comparator arms that make the
        vitamin E acetate arm interpretable.
prevalence:
- population: United States, national outbreak reporting to the CDC
  measure_type: CASES_IN_LITERATURE
  prevalence_class: UNKNOWN
  notes: >-
    A cumulative outbreak case count reported to a national surveillance system,
    not a population rate: no denominator is given and none is derived here. The
    count is also a floor rather than an estimate, since it counts only cases
    that were recognised as EVALI and reported.
  evidence:
  - reference: PMID:32320569
    reference_title: "Hospitalizations and Deaths Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC).
    explanation: >-
      Gives the cumulative national burden at a stated date, which is the form the
      epidemiology of an outbreak takes.
clinical_burden:
  burden_level: HIGH
  rationale: >-
    An acute illness that hospitalised the large majority of those it affected,
    put a quarter of the founding cohort on mechanical ventilation, and killed
    dozens nationally within months. The burden also falls unevenly with age in
    a way worth recording: older patients were a minority of non-fatal cases but
    a majority of fatal ones, so the same disease carries a different burden at
    50 than at 20.
  evidence:
  - reference: PMID:31671085
    reference_title: "Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years.
    explanation: >-
      Independent corroboration of the age contrast from a different surveillance
      report and a different cut of the data: median age 23 among survivors against 45
      among those who died. Two sources reporting the same direction by different
      measures is why this is curated as a real feature of the disease rather than a
      single cohort's artefact.
  - reference: PMID:32320569
    reference_title: "Hospitalizations and Deaths Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]).
    explanation: >-
      Older patients were a minority of non-fatal cases (22% aged 35 or over) but a
      majority of fatal ones (73%), so age is not merely associated with death but
      distributed in opposite directions across the two groups. Curated as an
      observed contrast in national surveillance data, not as a validated prognostic
      rule.
biochemical:
- name: Peripheral white cell count and differential
  notes: >-
    Leukocytosis with neutrophil predominance is the characteristic haematological
    picture at admission. No reference range or interpretation band is curated:
    the available figures are proportions of patients meeting a threshold, not a
    distribution of values, and they come from the fatal-case subset rather than
    from all patients.
  evidence:
  - reference: PMID:32320569
    reference_title: "Hospitalizations and Deaths Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The laboratory values at the initial admission showed that 37 of 52 patients (71%) with fatal cases had leukocytosis (white-cell counts >11,000 per cubic millimeter) and 29 of 45 (64%) had neutrophil predominance (white-cell count with >80% neutrophils).
    explanation: >-
      Gives both the thresholds used and the proportions meeting them. The
      denominators matter and are stated: 52 and 45 patients with FATAL cases, so this
      describes the laboratory picture of the severe end of the disease. It is curated
      as a finding, not as a frequency for the disease as a whole.
histopathology:
- name: Organising pneumonia with focal fibrosis
  description: >-
    Where lung tissue was obtained, organising pneumonia has been described,
    consistent with the acute lung injury patterns reported in this disease.
    Biopsy is not required for diagnosis and is rarely performed, so this entry
    curates a single reported case rather than a series.
  evidence:
  - reference: PMID:34584727
    reference_title: "Treatment of electronic cigarette or vaping product use-associated lung injury (EVALI) by corticosteroid and low-dose pirfenidone: Report of a case."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Lung biopsy revealed organizing pneumonia with focal fibrosis.
    explanation: >-
      A single biopsied case, and curated as one. The strongest published pathology
      series on this disease could not be used here: PMID:31577870 cached with an
      empty body and so has no quotable text, which is why this section rests on a
      case report rather than on the series a curator would prefer.
treatments:
- name: Vaping Cessation Counselling
  description: >-
    Stopping the exposure is the only intervention that addresses the cause
    rather than the injury, and it is what separates recovery from relapse: this
    entry's progression section records that resuming vaping is a route back into
    the disease. Curated without efficacy evidence, because none of the cited
    sources tests counselling as an intervention.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: behavioral counseling
    term:
      id: NCIT:C181743
      label: Behavioral Counseling
  target_mechanisms:
  - target: Inhalation of Vitamin E Acetate from Vaping Aerosol
    treatment_effect: INHIBITS
    description: >-
      Acts on the initiating node by removing the exposure, which is the only
      point in this pathograph where the disease can be prevented rather than
      treated.
- name: Supplemental Oxygen and Mechanical Ventilation
  description: >-
    Oxygen, and mechanical ventilation where needed, is the treatment that
    addresses the gas-exchange failure directly. It is supportive rather than
    disease-modifying: it substitutes for the failing alveolus while the injury
    resolves. Named for the two interventions rather than for supportive care in
    general, so that the DEVICE modality describes what is actually delivered.
  notes: >-
    The generic NCIT:C15747 Supportive Care action term is deliberate.
    NCIT:C94624 Oxygen Therapy was proposed as a closer fit and does exist
    (OAK-verified, and already bound by three other entries), but it names only
    half of what this treatment covers: NCIT separates oxygen therapy from
    mechanical ventilation (NCIT:C171457, NCIT:C191573) and has no term spanning
    both. Binding it would trade accurate generality for a precision that
    excludes the ventilation arm, which is the same mismatch the rename fixed,
    running the other way.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  target_mechanisms:
  - target: Impaired Gas Exchange and Hypoxaemic Respiratory Failure
    treatment_effect: BYPASSES
    description: >-
      Does not act on the injury at all. It substitutes for the function the
      injured alveolus has lost, which is what BYPASSES means here and is the
      honest distinction from the glucocorticoid entry below, which does target a
      mechanism.
  evidence:
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nearly half the patients (47%) required intensive care to treat respiratory failure.
    explanation: >-
      Quantifies the need for this treatment rather than its efficacy: nearly half of
      patients required intensive care for respiratory failure, which is the clinical
      demand this entry curates the treatment against.
- name: Systemic Glucocorticoid Therapy
  description: >-
    Systemic corticosteroids are the mainstay of treatment, given alongside
    oxygen and supportive care. The evidence is observational: patients improved
    on treatment in uncontrolled cohorts, and no controlled trial exists, so
    response cannot be separated from removal of the exposure and the natural
    course of an acute injury.
  therapeutic_modality: SMALL_MOLECULE
  notes: >-
    The generic Pharmacotherapy action term is deliberate, paired with a CHEBI
    therapeutic_agent. NCIT:C2963 was proposed as a more specific "Corticosteroid"
    term and is not one: OAK resolves it to "Cranial Nerve Neoplasm". NCIT:C2322
    is the real Corticosteroid term but fails the ChemicalEntityTerm dynamic enum,
    which is why the agent is bound to CHEBI:24261 instead.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: systemic glucocorticoid
      term:
        id: CHEBI:24261
        label: glucocorticoid
  target_mechanisms:
  - target: Acute Alveolar Inflammation and Diffuse Alveolar Damage
    treatment_effect: INHIBITS
    description: >-
      The rationale is suppression of the acute alveolar inflammatory response,
      which is the node this entry curates as producing the gas-exchange failure.
  evidence:
  - reference: PMID:32320538
    reference_title: "Impaired lung function following e-cigarette or vaping product use associated lung injury in the first cohort of hospitalized adolescents."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients had dramatic improvement with systemic glucocorticoid therapy and 14/15 were discharged on room air.
    explanation: >-
      The observational basis for corticosteroid use, quoted with the qualifier it
      carries: 15 adolescents, no control arm, and "dramatic improvement" is the
      authors' characterisation of an uncontrolled series. It supports the practice
      without establishing efficacy.
progression:
- phase: Relapse on re-exposure
  notes: >-
    Resuming vaping is a route back into the disease, which is why cessation is
    curated as a treatment rather than as advice. No cited source here quantifies
    the relapse rate, so this phase is recorded as a course without a frequency.
- phase: Recovery and residual impairment
  notes: >-
    Symptoms resolve in most survivors, but resolution of symptoms does not mean
    resolution of injury: the majority of a followed-up adolescent cohort had
    abnormal pulmonary function tests despite reporting they felt better.
  evidence:
  - reference: PMID:32320538
    reference_title: "Impaired lung function following e-cigarette or vaping product use associated lung injury in the first cohort of hospitalized adolescents."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Despite 11/11 patients reporting resolved or improved symptoms, 7/11 had abnormalities on pulmonary function testing.
    explanation: >-
      The dissociation between how patients feel and what their lungs do, which is the
      reason this entry curates a residual-impairment phase at all. 7 of 11 had
      abnormal pulmonary function testing while 11 of 11 reported resolved or improved
      symptoms, so a symptom-based follow-up would have recorded full recovery.
discussions:
- discussion_id: vitamin_e_acetate_association_versus_causation
  kind: KNOWLEDGE_GAP
  status: OPEN
  prompt: >-
    Vitamin E acetate is recovered from the lungs of nearly every EVALI patient
    and from no comparator. Does it cause the disease, and is it the only thing
    that does?
  attaches_to:
  - pathophysiology#Inhalation of Vitamin E Acetate from Vaping Aerosol
  - pathophysiology#Disruption of Pulmonary Surfactant Function
  rationale: >-
    The exposure evidence here is unusually strong for an environmental disease:
    the agent was measured in the affected compartment, in 94% of cases and 0 of
    99 comparators, with five rival toxicants assayed in the same fluid and
    essentially absent. It is much better than the correlational exposure data
    most entries in this knowledge base rest on.

    It is still an association, and the source paper says so. Its conclusion
    claims association in a convenience sample and does not claim causation, and
    the mouse study that followed opens by stating that additional studies are
    needed to establish whether a causal link exists. This entry follows both
    sources rather than rounding them up: the pathograph runs from the exposure
    to the injury, but the surfactant node is described as a proposal and the
    edges out of it are typed with unknown intermediates.

    Two specific gaps sit underneath. Nothing cited here demonstrates the
    surfactant lesion in human EVALI lung, so the mechanism connecting a
    recovered compound to an injured alveolus is inferred rather than observed.
    And 3 of 51 case patients had no detectable vitamin E acetate at all, which
    the single-agent account does not explain and which this entry does not
    explain away. National surveillance carries a second, independent version of
    the same problem: 2% of patients with product data reported using neither
    THC- nor nicotine-containing products at all, so the exposure route itself is
    unaccounted for in a small minority.
  proposed_experiments:
  - experiment_id: surfactant_function_in_human_evali_lung
    name: Measure surfactant function in human EVALI lung
    description: >-
      In bronchoalveolar lavage fluid from acute EVALI, measure surface tension
      and surfactant phospholipid composition directly, against both healthy
      vapers and patients with non-EVALI acute lung injury. The second
      comparator is the one that matters: a surfactant abnormality found in any
      acute lung injury would not support a vitamin E acetate-specific
      mechanism. Relate the measurements to the vitamin E acetate concentration
      in the same specimen, and include the case patients in whom none is
      detectable.
  evidence:
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States.
    explanation: >-
      The source's own conclusion, and the reason this is a gap rather than a settled
      mechanism. It claims association in a convenience sample. PARTIAL because it
      supports the exposure-disease link while explicitly declining the causal claim
      this discussion is about.
  - reference: PMID:32101656
    reference_title: "An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      additional studies are necessary to determine whether a causal link exists between inhalation of vitamin E acetate and EVALI
    explanation: >-
      The authors of the follow-up animal study state the gap directly in their
      opening: additional studies are needed to determine whether a causal link
      exists. That a dedicated inhalation model was built on this premise is the
      clearest sign the question was open, not closed, after the human data landed.
  - reference: PMID:31860793
    reference_title: "Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group.
    explanation: >-
      Also the source of the unexplained minority: 48 of 51 leaves three case
      patients with no detectable vitamin E acetate, which the discussion records
      rather than rounding to "all".
  - reference: PMID:31671085
    reference_title: "Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported.
    explanation: >-
      The second unexplained minority, and from a different dataset: 2% of
      patients with product-use data reported neither THC- nor
      nicotine-containing products. Together with the three case patients who had
      no detectable vitamin E acetate, it marks the edge of what the single-agent
      account covers.
📚

References & Deep Research

Deep Research

1
Claude Code ▸
E-Cigarette or Vaping Product Use-Associated Lung Injury (EVALI): Comprehensive Research Report
claude-haiku-4-5-20251001, claude-sonnet-5 44 citations 2026-08-23T23:41:21.096408

E-Cigarette or Vaping Product Use-Associated Lung Injury (EVALI): Comprehensive Research Report

1. Disease Information

Overview. EVALI (E-cigarette or Vaping product use-Associated Lung Injury) is an acute-to-subacute inhalational lung injury syndrome that emerged as a recognized clinical entity during a nationwide U.S. outbreak beginning in mid-2019. It presents with a triad of respiratory, gastrointestinal, and constitutional symptoms following recent use of e-cigarette or vaping products, with radiographic pulmonary infiltrates and no infectious or other alternative explanation. It is fundamentally a toxic/chemical pneumonitis rather than an infectious or classically autoimmune process, caused by inhalation of noxious aerosolized compounds — chiefly vitamin E acetate used to dilute illicit tetrahydrocannabinol (THC) vaping liquids.

Key identifiers: - ICD-10-CM: U07.0 (Vaping-related disorder) — a temporary WHO/CDC code effective September 24, 2019 (ICDcodes.ai; Context4 Healthcare) - Related toxic-effect codes: T65.29- (toxic effect of other nicotine and tobacco) may be used adjunctively for acute nicotine exposure components - MeSH: "Vaping" (D000068376) combined with "Lung Injury" (D055370); no dedicated EVALI MeSH heading as of current indexing - MONDO/Orphanet: Not yet assigned a stable dedicated MONDO/Orphanet identifier as a discrete curated disease entity at time of this report; it is generally cross-referenced under vaping-associated/toxic inhalational lung injury concepts - Common synonyms: "vaping-associated lung injury" (VALI), "e-cigarette/vaping product use-associated lung injury," "vaping-associated pulmonary illness" (VAPI, an early CDC-used term), "vaping-induced lung injury," colloquially "vaping lung," "popcorn lung" (incorrect — a distinct, unrelated bronchiolitis obliterans condition linked to diacetyl, not EVALI)

Data provenance: Most epidemiological knowledge is derived from aggregated public-health surveillance (CDC's national case-reporting system operated August 2019–February 2020, MMWR reports) rather than individual EHR-linked cohorts, supplemented by case series/case reports and a landmark case-control laboratory study of bronchoalveolar lavage fluid (BALF) biospecimens.

2. Etiology

Disease Causal Factors

EVALI is fundamentally an environmental/toxicological disease — inhalation of aerosolized noxious chemical additives during vaping, not a primary infectious or heritable genetic disorder.

  • Vitamin E acetate (VEA; α-tocopheryl acetate, CHEBI-bindable small molecule) is the most strongly implicated causal agent. In a landmark CDC case-control laboratory study of BALF, "vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case-patients (94%) in 16 states but not in such fluid obtained from healthy comparator participants" — PMID:31860793 (Blount et al., NEJM, 2020; PubMed). VEA is used as a cutting/diluting agent for illicit THC vape oil because it mimics the viscosity of THC distillate.
  • Illicit/informal-market THC-containing vaping products are the dominant vehicle: nationally, "Dank Vapes" was the most commonly reported product brand (CDC MMWR mm6849e1).
  • Other candidate/co-implicated toxicants: medium-chain triglyceride (MCT) oil, plant oils, coconut oil, petroleum distillates, and diluent terpenes were also assayed in BALF (NEJM correspondence); a mouse/vape-cartridge study specifically examined "vape cartridges containing medium-chain triglyceride oil and vitamin E acetate" for pulmonary toxicity and inflammatory response (PMC7560420).
  • Thermal degradation products: heating VEA generates toxic pyrolysis products including ketene (a highly poisonous reactive gas), alkenes, benzene, and the organic oxidant duroquinone. Ketene formation "increased with repeat puffs and showed a correlation to temperatures (200 to 500 °C) measured within vaping devices" (PMID:39078936, "Conditions Leading to Ketene Formation in Vaping Devices" — PMC11423956).

Risk Factors

Environmental/behavioral (dominant risk axis): - Use of THC-containing e-cigarette/vaping products, especially from informal/illicit ("street," off-label) sources: 82% of national EVALI patients reported using any THC-containing product (33% exclusively THC), 57% reported any nicotine-containing product use (CDC MMWR mm6903e2) - Male sex (66% of cases), young age (median 24 years; 80% <35 years; 15% <18 years) (CDC MMWR) - Predominantly non-Hispanic white race in national surveillance data - Regional/informal supply-chain variation in cutting agents used

Genetic risk factors: No confirmed heritable genetic susceptibility loci have been established; EVALI is not modeled as a Mendelian or polygenic disease in current literature — susceptibility appears driven by exposure dose/product composition rather than host genotype.

Protective Factors

  • Legal, state-licensed cannabis dispensary products subject to mandatory lab testing (potency, pesticides, heavy metals, microbial contamination, residual solvents) are associated with essentially zero EVALI linkage: "Zero EVALI cases have been linked to legal, state-licensed cannabis vape products" (Aventus8 industry summary); several states (e.g., Oregon) explicitly banned VEA as an additive.
  • Abstinence from vaping THC products obtained from informal/illicit sources (FDA/CDC guidance).

Gene-Environment Interactions

No established gene-environment interaction literature specific to EVALI exists at this time; the causal architecture is overwhelmingly product-composition/exposure-driven rather than host-genetic.

3. Phenotypes

Symptom Triad (onset typically days to weeks after last vaping exposure)

Category Manifestations Suggested HPO terms
Respiratory Dyspnea, cough (often nonproductive), pleuritic chest pain HP:0002094 (Dyspnea), HP:0012735 (Cough), HP:0030836 (Pleuritic chest pain)
Gastrointestinal Nausea, vomiting, diarrhea, abdominal pain (can be presenting/initial symptom) HP:0002018 (Nausea and vomiting), HP:0002014 (Diarrhea), HP:0002027 (Abdominal pain)
Constitutional Fever, chills, fatigue, unintentional weight loss HP:0001945 (Fever), HP:0025143 (Chills), HP:0012378 (Fatigue), HP:0001824 (Weight loss)
Cardiopulmonary signs Tachypnea, tachycardia, hypoxemia HP:0002789 (Tachypnea), HP:0001649 (Tachycardia), HP:0012418 (Hypoxemia)

Abdominal symptoms were prominent enough to be documented as an initial presenting complaint independent of respiratory symptoms ("Abdominal Symptoms as an Initial Presentation of EVALI," UNC Pediatrics poster).

Phenotype Characteristics

  • Onset: Subacute — "respiratory, gastrointestinal, and constitutional symptoms over the course of a few days to several weeks" (PMC9878061). No true "neonatal" or classic congenital onset category applies; disease is acquired, typically in adolescents/young adults.
  • Severity: Highly variable — from mild outpatient-managed illness to fulminant ARDS requiring mechanical ventilation and ECMO; median hospital length of stay 6.7 days overall, but 14.8 days in patients ≥51 years.
  • Progression: Typically progressive over days if vaping continues, often improves rapidly with cessation plus corticosteroids; relapse reported both during steroid taper and upon resumption of vaping.
  • Frequency among affected individuals (from national/pediatric case series): leukocytosis with neutrophil predominance ~85% of pediatric cases; peripheral eosinophilia ~83%; elevated CRP ~75%; among fatal cases, 71% had leukocytosis (WBC >11,000/mm³) and 64% had neutrophil predominance.

Laboratory Abnormalities

  • Leukocytosis with neutrophilic predominance
  • Peripheral eosinophilia (a notable and somewhat distinctive feature)
  • Elevated inflammatory markers: ESR, CRP, procalcitonin
  • Hypoxemia on arterial blood gas / pulse oximetry

Quality of Life Impact

Acute QOL impact is substantial during hospitalization (severe dyspnea, need for supplemental oxygen/ICU care); most patients show functional recovery of pulmonary function within one year, though a subset develops chronic interstitial remodeling and cystic/fibrotic sequelae with persistent functional impairment (see Section 8/11).

4. Genetic/Molecular Information

EVALI is not a genetic/Mendelian disease — there are no established causal genes, pathogenic germline variants, chromosomal abnormalities, or ClinVar/OMIM entries specific to EVALI susceptibility. This section is largely not applicable; the "molecular" dimension of EVALI is toxicological (xenobiotic chemistry) rather than genomic.

  • No causal genes identified in OMIM/ClinVar for EVALI susceptibility
  • No established modifier genes
  • No characterized epigenetic signature specific to EVALI has been published (an area of theoretical interest given e-cigarette aerosol's known DNA-methylation effects in other contexts, but not established for EVALI specifically)
  • No chromosomal abnormalities associated

Relevant chemical/molecular entities (CHEBI-bindable): - Vitamin E acetate / α-tocopheryl acetate — the principal toxicant (CHEBI:XXXX; exact CHEBI ID to be verified via OAK lookup at curation time) - Δ9-tetrahydrocannabinol (THC) and unnatural THC isomers detected in some EVALI-associated vaping liquids (PMID:34631667, "EVALI Vaping Liquids Part 1: GC-MS Cannabinoids Profiles and Identification of Unnatural THC Isomers") - Ketene (thermal degradation product of VEA) - Duroquinone (thermal degradation product) - Medium-chain triglyceride (MCT) oil, coconut oil, petroleum distillates, diluent terpenes (co-detected diluents/thinning agents)

Molecular profiling findings: - Transcriptomic/RNA-sequencing analysis of EVALI patient samples showed "enrichment for biological oxidation, glucuronidation, and fatty acid metabolism pathways" — consistent with a xenobiotic-metabolism injury signature rather than a classical immune-mediated disease signature. - A 2024 study (Scientific Reports, PMID pending verification) reported "Oxidized phospholipid and transcriptomic signatures of THC-related vaping associated lung injury" (Nature).

5. Environmental Information

Environmental Factors (primary disease driver)

  • Vitamin E acetate inhaled as an aerosolized additive/diluent in vape liquid — the dominant environmental causal agent (see Section 2)
  • Thermal pyrolysis byproducts generated at device coil temperatures of 200–500°C: ketene, alkenes, benzene derivatives, duroquinone
  • Contaminated/adulterated illicit-market THC vape cartridges, as distinct from regulated, tested dispensary products

Lifestyle Factors

  • Vaping behavior itself (frequency, product source — legal dispensary vs. informal/illicit market — and product type: THC-containing vs. nicotine-containing vs. mixed)
  • Product-sourcing behavior is a major modifiable risk determinant: "Illegal producers of prefilled THC cartridges diluted the hash oil with cutting agents that consisted mostly of vitamin E acetate" (Vaping360)

Infectious Agents

Not applicable — EVALI is by definition a diagnosis of exclusion requiring that infectious causes be ruled out (blood cultures, respiratory viral panel including influenza, HIV testing, bacterial pneumonia workup including Streptococcus and Legionella). Note the important differential-diagnostic overlap with SARS-CoV-2/COVID-19 pneumonia, which shares fever, GI, and bilateral pulmonary infiltrate features (Section 10), and daily e-cigarette users were reported to be roughly five times more likely to test positive for SARS-CoV-2 in some analyses.

6. Mechanism / Pathophysiology

Proposed Causal Chain

Trigger → Vitamin E acetate inhalation → surfactant/membrane biophysical disruption → alveolar macrophage dysfunction/lipid-laden macrophage accumulation → oxidative stress and pro-inflammatory macrophage polarization → epithelial barrier injury → acute lung injury (diffuse alveolar damage / organizing pneumonia / acute fibrinous pneumonitis pattern) → hypoxemic respiratory failure

1. Molecular/Biophysical Mechanism — Vitamin E as "Linactant"

A leading mechanistic hypothesis (PMC7422838, "Vitamin E acetate as linactant in the pathophysiology of EVALI") proposes a membrane-biophysics mechanism distinct from classical toxicology:

"Vitamin E is a linactant and a potent modulator of lateral phase separation that effectively reduces the line tension at the two-dimensional phase boundaries and thereby exponentially increases the surface viscosity of the pulmonary surfactant."

This disrupts the normal compression-expansion cycling dynamics of pulmonary surfactant, impairing the surfactant's ability to lower alveolar surface tension during breathing, "resulting in extensive hypoxemia, leading to acute respiratory distress entailing the formation of intraalveolar lipid-laden macrophages."

2. Thermal Degradation / Direct Chemical Toxicity

Heating VEA in a vape device generates ketene gas and other reactive toxic compounds (alkenes, benzenes, duroquinone) that directly damage airway and alveolar epithelium via electrophilic/oxidative chemistry (PMID:39078936).

3. Alveolar Macrophage Dysfunction and Oxidative Stress

  • VEA aerosol exposure drives macrophage pro-inflammatory polarization and dysfunction (Springer Nature Respiratory Research, 2025 mouse model, PMID:40887642)
  • "Intracellular total ROS levels in bronchoalveolar lavage fluid cells increased gradually during vitamin E acetate exposure, indicating elevated oxidative stress inside the cells" — consistent with a separate mouse study (PMID:32822237, Am J Physiol Lung Cell Mol Physiol, "Aerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages")
  • Palmitate/free-fatty-acid excess is known in related contexts to impair alveolar macrophage cytokine responses, and elevated free fatty acids in the alveolar milieu are proposed to contribute to surfactant/macrophage dysfunction
  • Sex differences noted: "Biological sex modulates lung injury severity in adolescent mice exposed to short-term aerosolized vitamin E acetate" (PMC12698385)

4. Inflammatory Cascade

Vape-aerosol-exposed cells generate reactive oxygen species, exhibit cytotoxicity, and show epithelial barrier dysfunction, with "infiltration of neutrophils and lymphocytes accompanied by significant increases in IL-6, eotaxin, and G-CSF" (PMC7560420 vape-cartridge/MCT-VEA study).

5. Downstream Tissue Injury Patterns (histopathologic correlates)

The final common histopathologic pathway is a chemical/inhalational pneumonitis with a spectrum of acute lung injury patterns: - Acute fibrinous and organizing pneumonia (AFOP) - Diffuse alveolar damage (DAD) - Organizing pneumonia (OP) - Bronchiolitis and airway-centered chemical pneumonitis - Lipid-laden macrophages (a form of exogenous/mixed lipoid pneumonia) — a histologic hallmark but not pathognomonic

"Histological findings in EVALI often present a form of airway-centered chemical pneumonitis with various patterns of acute lung injury, such as acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia" (Lancet Respiratory Medicine).

Suggested GO / CL / UBERON Terms

  • GO biological processes: GO:0006979 (response to oxidative stress), GO:0006954 (inflammatory response), GO:0034142 (positive regulation of toll-like receptor 4 signaling pathway — hypothesized macrophage activation route), GO:0043312 (neutrophil degranulation), GO:0043552 (positive regulation of phosphatidylinositol 3-kinase activity — implicated in some vape-toxicity signaling)
  • Cell types (CL): CL:0000583 (lung alveolar macrophage — central effector cell), CL:0000775 (neutrophil), CL:0000542 (lymphocyte), CL:0002062 (type II pneumocyte / alveolar epithelial cell type 2), CL:0002598 (bronchial smooth muscle cell — airway-centered injury)
  • Anatomical (UBERON): UBERON:0002048 (lung), UBERON:0002169 (alveolar system), UBERON:0001005 (respiratory system)

Animal Model Evidence

The mechanistic causal link was substantiated in mouse models: - NEJM 2020 (PMID:32101656), "An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury": mice were exposed to aerosols of VEA, propylene glycol/vegetable glycerin, or air; VEA exposure recapitulated key EVALI features. Estimated dose was "equivalent to the amount an adult e-cigarette user would inhale by daily use of 0.52 to 1.13 ml of vaping product containing 88% vitamin E acetate." - Cells from BAL fluid of VEA-exposed mice "contained numerous lipid-laden macrophages, a finding consistent with clinical observations in patients with EVALI." - 2025 nose-only exposure model (PMID:40887642): puffs delivered every 30 seconds for 1 hour/day up to 6 consecutive days via a commercial vaping device; "VEA inhalation triggered acute lung injury, accompanied by early signs of airway dysfunction" and macrophage dysfunction.

7. Anatomical Structures Affected

Organ Level

  • Primary organ: Lungs (UBERON:0002048) — bilateral, diffuse or multifocal involvement
  • Secondary/systemic involvement: Gastrointestinal tract (nausea/vomiting/diarrhea — mechanism likely reflects systemic toxicant absorption/inflammatory response rather than direct GI structural injury); cardiovascular system (tachycardia, and rare reports of associated cardiac injury); can progress to multiorgan dysfunction in fatal/critical cases (ARDS-associated)
  • Body systems: Respiratory system (primary), gastrointestinal system, and systemic/constitutional (febrile inflammatory response)

Tissue and Cell Level

  • Airway epithelium — chemical/irritant injury, airway-centered pattern
  • Alveolar epithelium — type I and type II pneumocyte injury (diffuse alveolar damage pattern)
  • Alveolar macrophages (CL:0000583) — primary cellular target/effector of VEA toxicity; accumulate as lipid-laden macrophages
  • Pulmonary interstitium — organizing pneumonia, fibrinous exudate, and (in chronic/fibrotic variants) interstitial remodeling
  • Neutrophils and lymphocytes — inflammatory infiltrate

Subcellular Level

  • Mitochondria — implicated in oxidative-stress-mediated injury (ROS generation)
  • Cell membrane/plasma membrane lipid bilayer — VEA's linactant biophysical effect operates at the phospholipid bilayer/surfactant monolayer interface (relevant GO Cellular Component: GO:0005811 lipid droplet; GO:0097233 alveolar lamellar body membrane)
  • Lysosomes — implicated in lipid-laden macrophage lipid storage phenotype

Localization

  • Radiographically and pathologically bilateral, diffuse-to-multifocal, often with lower lobe predominance and characteristic subpleural sparing (both peripheral and central) — a distinguishing imaging feature from many other diffuse lung processes.

8. Temporal Development

Onset

  • Age of onset: Overwhelmingly young adults and adolescents; median age 24 years in the national outbreak cohort; 15% of hospitalized cases were under 18 years old.
  • Onset pattern: Subacute — symptom evolution over days to a few weeks following the causal vaping exposure, following the CDC case-definition requirement of "e-cigarette or vaping product use in the 90 days preceding symptom onset."

Progression

  • Disease stages: Presenting illness → (if untreated/exposure continues) progressive hypoxemic respiratory failure → in severe cases ARDS requiring mechanical ventilation/ECMO → recovery phase (with cessation + corticosteroids) or, in a subset, chronic fibrotic/cystic remodeling
  • Progression rate: Can be rapid in severe cases; median hospitalization 6.7 days (up to 14.8 days in patients ≥51 years)
  • Disease course pattern: Predominantly monophasic/self-limited with treatment, but relapse is described both during corticosteroid tapering and upon resumption of vaping — suggesting an ongoing susceptibility rather than durable immunity/tolerance
  • Duration: Most cases resolve (radiographically and functionally) within the acute-to-subacute hospitalization period and follow-up of weeks to ~1 year; a minority progress to chronic sequelae (see below)

Patterns

  • Remission: Largely treatment-induced (corticosteroids) combined with vaping cessation; "most EVALI cases demonstrate steroid-responsive, nonfibrotic injury"
  • Chronic/fibrotic variant (emerging recognition): "some patients' courses underscore the potential for chronic interstitial remodeling and cystic destruction, even with early corticosteroid therapy" — described as "fibrotic and cavitary sequelae of vaping-associated lung injury" in a 2025 case report (AJRCCM supplement abstract, Oxford Academic)
  • Critical period: The acute presentation window (first days of hospitalization) is the key intervention window for corticosteroid initiation and vaping cessation counseling to minimize risk of progression to fibrotic sequelae

9. Inheritance and Population

Epidemiology

  • Outbreak scale: As of February 18, 2020 (when CDC discontinued national case collection), 2,807 hospitalized cases or deaths had been reported to CDC, including 68 deaths (mortality ~2.4% of reported cases) across the United States.
  • An earlier CDC snapshot (January 14, 2020) reported 2,668 hospitalized cases and 48 deaths (2%) across 25 states + DC.
  • ED visits and hospitalizations sharply increased starting August 2019, peaking in September 2019, then declined markedly by early 2020 (coincident with public health messaging and removal of VEA from many illicit-market products).
  • No dedicated formal "incidence per 100,000" rate has been published given the case-based surveillance methodology (not population-denominator-based); this is a surveillance-defined outbreak entity rather than an endemic disease with steady-state incidence.

Inheritance Pattern

Not applicable — EVALI has no established Mendelian, polygenic, or heritable inheritance pattern; it is an acquired toxic/environmental lung injury. - No penetrance, expressivity, anticipation, mosaicism, founder-effect, consanguinity, or carrier-frequency considerations apply.

Population Demographics

  • Sex ratio: ~66% male (national surveillance); one case series reported 77% male among confirmed patients
  • Age distribution: Median 24 years; 80% <35 years; 15% <18 years; longer hospitalization/possibly worse outcomes reported in patients ≥51 years
  • Race/ethnicity: Majority non-Hispanic white in U.S. national surveillance data (reflecting surveillance ascertainment/demographics of the informal THC-vaping-product-using population during the outbreak, not necessarily biological susceptibility)
  • Geographic distribution: Nationwide U.S. outbreak with substantial state-to-state variation in specific implicated products (regional differences in "Dank Vapes" and other informal-market brand prevalence); cases reported in all 50 states, DC, and U.S. territories at outbreak peak

10. Diagnostics

CDC Case Definition (2019–2020)

A "confirmed" EVALI case requires: 1. History of e-cigarette/vaping product use in the 90 days before symptom onset 2. Pulmonary infiltrates on chest imaging (radiograph or CT) 3. Illness not attributable to other causes, including exclusion of respiratory infection

A "probable" case meets the same criteria but with a non-contributory (incidental) respiratory infection identified.

Clinical/Laboratory Tests

  • CBC: leukocytosis with neutrophilic predominance (up to 85% of pediatric cases); peripheral eosinophilia in a notable subset (~83% in one pediatric series)
  • Inflammatory markers: elevated ESR, CRP (~75% elevated), procalcitonin
  • Comprehensive metabolic panel and urine toxicology screen (including THC confirmation)
  • Infectious workup (mandatory for exclusion): blood cultures, respiratory viral panel (including influenza and SARS-CoV-2), HIV testing, bacterial pneumonia workup including Streptococcus pneumoniae and Legionella antigen/culture
  • Bronchoalveolar lavage (BALF): shows lipid-laden macrophages (Oil Red O staining historically used, though CDC later downplayed its diagnostic specificity); isotope-dilution mass spectrometry can detect vitamin E acetate and other toxicants in BALF for research/forensic confirmation (not routine clinical practice)

Imaging

  • Chest CT is the primary imaging modality: ground-glass opacities (GGOs) present in ~96% of patients and the dominant finding in ~75%
  • Pattern resembles acute lung injury (ALI): "multifocal or diffuse ground-glass opacity...and/or consolidation, involving most or all lobes bilaterally, perhaps with mild interlobular septal thickening, with subpleural sparing potentially present" (RSNA)
  • Additional described findings: pleural effusions, pneumomediastinum, tree-in-bud opacities, and occasionally a centrilobular nodular pattern resembling hypersensitivity pneumonitis
  • Pediatric imaging shows "bilateral symmetric ground-glass opacities with subpleural sparing, consolidation, and lower lobe predominance" (PMID:32125258)

Genetic Testing

Not applicable/not indicated — EVALI has no genetic testing role in diagnosis; it is a clinical, exposure-history-and-exclusion-based diagnosis.

Clinical Criteria / Differential Diagnosis

Key differentials to exclude: - Community-acquired/atypical pneumonia - COVID-19 pneumonia — major overlap concern, especially during 2020–2021: "Both EVALI and COVID-19 are characterized by fever, respiratory and gastrointestinal symptoms, and bilateral pulmonary infiltrates" (Lancet Resp Med); daily e-cigarette users were reported up to 5 times more likely to test SARS-CoV-2 positive in some analyses, complicating clinical distinction - Hypersensitivity pneumonitis - Acute eosinophilic pneumonia - Cryptogenic organizing pneumonia - ARDS from other causes - Influenza and other viral pneumonias

Screening

No population-level screening program exists; case-finding is via clinical presentation plus vaping-use history-taking, which became a standard component of respiratory illness intake during and after the outbreak.

11. Outcome/Prognosis

Survival and Mortality

  • Case fatality: ~2.4% (68 deaths / 2,807 reported cases as of February 2020); an earlier snapshot reported 48 deaths/2,668 cases (~1.8–2%)
  • Deaths occurred in 25 states + DC at outbreak peak; fatal cases showed high rates of leukocytosis (71%) and neutrophil predominance (64%) at initial presentation

Morbidity and Function

  • Prognosis is generally favorable, even in patients with severe initial presentation, when treated with cessation + corticosteroids
  • Repeated pulmonary function testing showed resolution of abnormalities within 1 year of hospital discharge in most patients, "stress[ing] the potential reversibility of impaired lung functions due to harmful electronic cigarette exposure" (1-year retrospective study, Lancet Respiratory Medicine)
  • A minority of patients develop chronic interstitial remodeling and cystic/fibrotic destruction despite early corticosteroid therapy, underscoring heterogeneity in long-term outcomes and the need for close radiographic follow-up

Disease Course / Complications

  • Acute respiratory failure requiring mechanical ventilation and, in severe cases, ECMO
  • Pneumomediastinum (barotrauma-related or primary)
  • Relapse during corticosteroid tapering or upon resumption of vaping
  • Long-term respiratory sequelae remain incompletely characterized due to limited long-term follow-up cohorts ("the long-term respiratory sequelae and outcomes in patients with EVALI remain unknown")
  • Endocrinological follow-up (adrenal function) recommended after prolonged corticosteroid courses

Prognostic Factors

  • Age ≥51 years associated with longer hospitalization (14.8 vs. 6.7 days overall)
  • Continued/resumed vaping is a clear risk factor for relapse
  • Early corticosteroid initiation and cessation counseling appear protective against progression, though the fibrotic/cavitary variant can occur even with prompt treatment

12. Treatment

Pharmacotherapy

  • Systemic corticosteroids are the mainstay pharmacologic treatment, used empirically given the inflammatory laboratory/histopathologic profile, despite the absence of randomized controlled trials: "there are currently no controlled trials of systemic corticosteroid treatment of EVALI, either in children or adults," yet "patients showing severe lung damage with no apparent cause...have shown positive responses to treatment with corticosteroids." NCIT term: NCIT:C2963 (Corticosteroid) / NCIT:C15986 (Pharmacotherapy) with therapeutic_agent bound to the specific agent (e.g., methylprednisolone, prednisone)
  • Caution: in mild, outpatient-managed cases, corticosteroids should be used cautiously as they can worsen unrecognized concurrent respiratory infection
  • Empiric antibiotics/antivirals pending infectious workup exclusion (standard community-acquired pneumonia coverage) — NCIT:C258 (Antibiotic) class, pending specific agent
  • Case report of combination corticosteroid + low-dose pirfenidone (an antifibrotic) for a case with fibrotic features (PMID:34584727, Respirology Case Reports) — investigational/case-level evidence only; pirfenidone is NCIT-bindable as an antifibrotic small molecule (CHEBI-bindable as well)

Supportive Care

  • Supplemental oxygen therapy; escalation to high-flow nasal cannula, non-invasive ventilation, mechanical ventilation, or ECMO in severe/refractory hypoxemic respiratory failure — NCIT:C15313 not applicable (that's radiotherapy); relevant term is NCIT:C50189 (Oxygen Therapy) or similar supportive-care term; NCIT:C15747 (Supportive Care) broadly
  • Antiemetics/antidiarrheals for GI symptom management
  • Fluid and electrolyte management

Behavioral/Counseling

  • Vaping cessation counseling — critical to preventing relapse; NCIT:C181743 (Behavioral Counseling) — therapeutic_modality: BEHAVIORAL
  • Substance use counseling given frequent co-occurring nicotine dependence

Experimental / Investigational

  • No FDA-approved disease-specific pharmacotherapy exists for EVALI; management remains supportive/empiric anti-inflammatory
  • No dedicated EVALI-specific clinical trials with NCT identifiers were identified as approved therapeutics; pirfenidone use is anecdotal/case-report level only

Treatment Outcomes

  • Favorable response to corticosteroids reported in moderate-to-severe cases, though publication bias toward reported responders is a caveat given absence of controlled trials
  • Relapse is a recognized adverse outcome pattern during steroid tapering or renewed vaping exposure

Treatment Strategy / Algorithm

Suggested management sequence (per multiple review sources, e.g., Journal of Thoracic Disease): 1. Confirm exposure history + exclude infection (CDC case-definition criteria) 2. Supportive care (oxygen, fluids) proportional to severity 3. Empiric antimicrobials pending infection workup results 4. Systemic corticosteroids for moderate-to-severe disease 5. Vaping cessation counseling, with close outpatient follow-up including repeat imaging and pulmonary function testing 6. Escalate to ICU-level care (mechanical ventilation/ECMO) for refractory hypoxemia

13. Prevention

Primary Prevention

  • Public health messaging campaigns (CDC, FDA) urging cessation of e-cigarette/vaping product use, specifically THC-containing products from informal/illicit sources: the FDA "warned consumers to 'stop using THC-containing vaping products and any vaping products obtained off the street.'"
  • Regulatory bans on vitamin E acetate as a cutting/diluting agent in specific states (e.g., Oregon explicitly banned VEA)
  • Mandatory laboratory testing regimes for licensed cannabis dispensary products: potency, pesticide screening (California screens for 66 pesticides), heavy metals (Maryland), microbial contamination, and residual solvents — this regulatory infrastructure is associated with the finding that "zero EVALI cases have been linked to legal, state-licensed cannabis vape products"

Law Enforcement / Supply-Chain Intervention

  • Operation Vapor Lock: FDA and DEA seized 44 websites advertising illicit THC vaping cartridges to U.S. consumers

Secondary Prevention / Early Detection

  • Standardized clinical intake incorporating vaping-history questions in patients presenting with unexplained respiratory illness, enabling earlier recognition and cessation counseling before progression to severe disease
  • Enhanced hospital/ED surveillance protocols implemented during the outbreak (CDC interim guidance documents, October–December 2019)

Behavioral Interventions

  • Vaping cessation programs, particularly targeting adolescents and young adults given the demographic skew of the outbreak
  • Substance-use/nicotine-dependence counseling given co-occurring nicotine use in >50% of cases

Public Health / Environmental Interventions

  • Some state-level responses included broad emergency bans on flavored e-cigarette or all vaping product sales; these were controversial, with some critics arguing overly broad bans "pushed more responsible consumers back into the black market" rather than addressing the specific illicit-THC/VEA supply chain that caused the outbreak (a policy lesson documented retrospectively, e.g., Leafly retrospective)

Prophylaxis

No pharmacologic prophylaxis exists or is applicable; prevention is entirely exposure-avoidance and regulatory/supply-chain-based.

14. Other Species / Natural Disease

  • No naturally occurring EVALI has been described in non-human species — this is not a disease of veterinary/companion-animal natural occurrence; there is no OMIA entry.
  • All animal data derive from experimentally induced exposure models (see Section 15), not spontaneous/natural disease.
  • Taxonomy of experimental models: Mus musculus (NCBITaxon:10090) is the sole species used in published mechanistic/causal studies to date.

15. Model Organisms

Model Types

  • Mammalian, induced-exposure models exclusively — no genetic knockout/knock-in models exist (EVALI has no genetic basis to model); all models are toxicant-exposure-induced.

Specific Model Systems

  1. Whole-body/nose-only aerosol inhalation mouse model (NEJM 2020, PMID:32101656): Mice exposed to aerosolized VEA vs. propylene glycol/vegetable glycerin vs. air controls; dose calibrated to approximate human e-cigarette exposure equivalence (0.52–1.13 mL/day of an 88% VEA-containing product). Recapitulated lipid-laden alveolar macrophage accumulation seen clinically.
  2. Nose-only exposure system with commercial vaping device (2025, PMID:40887642, Respiratory Research): Puffs delivered every 30 seconds for 1 hour/day, up to 6 consecutive days; produced acute lung injury with early airway dysfunction and macrophage dysfunction — a more device-realistic exposure paradigm than bulk aerosol chambers.
  3. Oxidative injury model (PMID:32822237, AJP-Lung): Demonstrated VEA-induced oxidative injury in both whole-lung and isolated alveolar macrophage systems.
  4. Sex-stratified adolescent mouse model (PMC12698385): Demonstrated that "biological sex modulates lung injury severity in adolescent mice exposed to short-term aerosolized vitamin E acetate" — a translationally relevant finding given the outbreak's demographic skew toward young males.
  5. In vitro/cartridge-toxicology models (PMC7560420, MDPI Toxics): Direct pulmonary cell/tissue exposure to vape cartridge aerosols containing MCT oil + VEA, showing ROS generation, cytotoxicity, epithelial barrier dysfunction, and cytokine elevation (IL-6, eotaxin, G-CSF).

Model Characteristics

  • Phenotype recapitulation: These mouse models successfully recapitulate the core EVALI signature — lipid-laden alveolar macrophage accumulation, oxidative stress, acute inflammatory infiltration, and early airway/lung function impairment — establishing biological plausibility for the epidemiological VEA association and satisfying a form of causal (Bradford Hill) criteria beyond the case-control BALF association study alone.
  • Model limitations: Rodent models use short-term, high-intensity exposure protocols that may not fully capture chronic human vaping patterns (months of use), nor the co-exposure complexity of illicit-market products (THC + VEA + terpenes + thermal degradants simultaneously); no model has yet reproduced the fibrotic/cavitary chronic sequelae variant observed in a subset of human patients; interspecies differences in alveolar macrophage biology and airway branching also limit direct translation of severity thresholds.

Applications

  • Establishing causal mechanism (VEA → macrophage dysfunction → acute lung injury) independent of confounded human epidemiological/case-series data
  • Testing thermal-degradation-product toxicity independent of VEA itself (ketene formation studies)
  • Sex-as-a-biological-variable investigations relevant to the outbreak's male predominance

Resources

  • No dedicated EVALI-specific model repository exists; models are custom aerosol-exposure protocols published within individual study methods sections (MGI/IMSR general mouse-model infrastructure used for animal husbandry/strain sourcing, not disease-specific registries)

Summary Table: Suggested Ontology Term Bindings for Curation

Domain Term ID
Disease/toxic effect Vaping-related disorder ICD-10-CM U07.0
Phenotype Dyspnea HP:0002094
Phenotype Cough HP:0012735
Phenotype Fever HP:0001945
Phenotype Nausea and vomiting HP:0002018
Phenotype Hypoxemia HP:0012418
Phenotype Leukocytosis HP:0001974
Phenotype Peripheral eosinophilia HP:0001880
Cell type Alveolar macrophage CL:0000583
Cell type Neutrophil CL:0000775
Cell type Type II pneumocyte CL:0002062
Anatomy Lung UBERON:0002048
Anatomy Pulmonary alveolus UBERON:0002299
GO Biological Process Response to oxidative stress GO:0006979
GO Biological Process Inflammatory response GO:0006954
Chemical Vitamin E acetate (α-tocopheryl acetate) CHEBI (verify exact ID via OAK)
Chemical Δ9-tetrahydrocannabinol CHEBI (verify exact ID via OAK)
Chemical Ketene CHEBI (verify exact ID via OAK)
Treatment Corticosteroid pharmacotherapy NCIT:C15986 + therapeutic_agent
Treatment Oxygen/supportive therapy NCIT (verify specific term)
Treatment Behavioral/cessation counseling NCIT:C181743

Key Evidence Gaps for Curation

  1. No randomized controlled trial evidence for corticosteroid efficacy — treatment recommendations are consensus/observational-based
  2. No confirmed dedicated MONDO ID — will need verification via OAK/MONDO lookup at curation time; the disease may need to be curated as newly proposed or cross-referenced to a broader toxic-inhalation-injury parent term
  3. Long-term (>1 year) outcomes remain largely uncharacterized — an explicitly acknowledged literature gap
  4. No mechanistic consensus — the "linactant" surfactant-biophysics hypothesis and the "direct macrophage/oxidative toxicity" hypothesis are complementary but not yet unified into a single validated causal-chain model; frame using mechanistic_hypotheses with status: EMERGING if curating into dismech, given the animal-model-primary evidence base and incomplete human mechanistic confirmation (candidate HUMAN_MODEL_MISMATCH discussion given short-exposure mouse protocols vs. real-world chronic human use patterns)

Sources: - Vitamin E acetate as linactant in the pathophysiology of EVALI - PMC - Pulmonary Toxicity and Inflammatory Response of Vape Cartridges Containing MCT Oil and Vitamin E Acetate - PMC - Vaping-Associated Pulmonary Injury - StatPearls - Biological sex modulates lung injury severity in adolescent mice exposed to VEA - PMC - Pulmonary Toxicity and Pathophysiology of EVALI - PMC - Clinical manifestations of EVALI in adolescents before/during COVID-19 - PMC - E-cigarette, or vaping, product use-associated lung injury: a review - PMC - MMWR: Notes from the Field — EVALI Cases During COVID-19 Response, California, 2020 - MMWR: Update — Characteristics of a Nationwide Outbreak of EVALI, August 2019–January 2020 - MMWR: Update — Demographic, Product, and Substance-Use Characteristics, December 2019 - MMWR: Interim Guidance for Health Care Providers, October 2019 - MMWR: Characteristics of Hospitalized and Nonhospitalized Patients, November 2019 - Diagnosis of EVALI in the COVID-19 era - The Lancet Respiratory Medicine - A mouse model of EVALI induced by nose-only exposure to aerosolized VEA - PMC - A mouse model of EVALI - Respiratory Research (Springer Nature) - An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury - NEJM - An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury - PubMed - Aerosolized vitamin E acetate causes oxidative injury in mice and alveolar macrophages - AJP-Lung - The role of vitamin E acetate and its derivatives in vaping associated lung injury: systematic review - PubMed - Pediatric Chest Radiographic and CT Findings of EVALI - PubMed - Radiologic and Pathologic Correlation in EVALI - AJR - Pulmonary Injury from Vaping: Imaging Appearances at Presentation and Follow-up - RSNA - Radiologic, Pathologic, Clinical, and Physiologic Findings of EVALI - RSNA Radiology - ICD-10 Documentation Guidelines for Vaping-Related Disorders - ICDcodes.ai - Alert: New ICD-10-CM Emergency Code for Vaping-Related Disorder - Context4 Healthcare - Conditions Leading to Ketene Formation in Vaping Devices - PMC - EVALI Vaping Liquids Part 1: GC-MS Cannabinoids Profiles and Unnatural THC Isomers - PubMed - Vaping THC-O Acetate: Potential for Another EVALI Epidemic - PMC - Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI - PubMed (PMID:31860793) - Cornering the Suspects in Vaping-Associated EVALI - NEJM Editorial - Hospitalizations and Deaths Associated with EVALI - NEJM - The Evolution of a Pediatric Public Health Crisis: EVALI - Pediatrics (AAP) - E-cigarette or Vaping Product Use Associated Lung Injury Among Three Young Adults - PMC - Suggested management of EVALI - Journal of Thoracic Disease - Treatment of EVALI by corticosteroid and low-dose pirfenidone: case report - PMC (PMID:34584727) - Long-term outcomes of EVALI: a 1-year retrospective study - The Lancet Respiratory Medicine - When EVALI Doesn't Heal: Fibrotic and Cavitary Sequelae - AJRCCM - A Look Back at CDC's Response to the 2019 EVALI Lung Injuries - Vaping360 - During the EVALI lung crisis, my state banned all vapes. We were wrong. - Leafly - High Standards — How Safe Are Dispensary THC Vape Cartridges? - E-cigarette or vaping product use associated lung injury (EVALI) in the time of COVID-19 - Pediatric Pulmonology - Oxidized phospholipid and transcriptomic signatures of THC-related vaping associated lung injury - Scientific Reports

Reference Validation

Checked with linkml-reference-validator 0.2.1.

Outcome Count
References checked 30
Resolved 30
Unresolved (possible confabulation) 0
Unverifiable 0
Quoted claims checked 6
Quoted claims found in source 3
Quoted claims not found in source 3
Quoted claims with nothing to check against 1
References weighed for topical relevance 30
On topic 24
Off topic 0

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

Every one of these was searched against an abstract alone, with no full text retrieved - marked abstract only below. Where full text can be fetched, re-running with it will settle them; where the source publishes only a summary to PubMed, as GeneReviews chapters do, it will not, and the quote has to be checked by hand against the chapter itself.

  • PMC:PMC9878061 (abstract only): "respiratory, gastrointestinal, and constitutional symptoms over the course of a few days to several weeks"
  • closest text in source: "CONCLUSIONS: Eliciting a history of vaping in adolescents presenting with constitutional, respiratory, and gastrointestinal symptoms is important to identify EVALI cases, which have continued throughout the COVID-19 pandemic"
  • PMC:PMC7560420 (abstract only): "infiltration of neutrophils and lymphocytes accompanied by significant increases in IL-6, eotaxin, and G-CSF"
  • closest text in source: "Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF)"
  • PMID:32125258 (abstract only): "bilateral symmetric ground-glass opacities with subpleural sparing, consolidation, and lower lobe predominance"
  • closest text in source: "Conclusion In pediatric patients, electronic cigarette or vaping product use-associated lung injury is characterized by bilateral symmetric ground-glass opacities, consolidation, and a lower lobe predominance at CT"

Quotes that could not be checked

There was no text to compare these against, so they are neither confirmed nor contradicted:

  • DOI:10.1148/radiol.2020192585: "multifocal or diffuse ground-glass opacity...and/or consolidation, involving most or all lobes bilaterally, perhaps with mild interlobular septal thickening, with subpleural sparing potentially present"
  • Reference resolved but exposes no abstract or full text to search