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Vaping Associated Pulmonary Injury (VAPI)

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CONTENTS

introduction & current cluster of VAPI cases

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Currently there is a cluster of cases of VAPI under investigation by the Centers of Disease Control.  This situation is rapidly evolving; the information below will be updated as possible (with the understanding that it remains incomplete currently).

epidemiology
  • Most patients are young (average age ~20 years old), with a male predominance.
  • ~80% of patients report a history of vaping with tetrahydrocannabinol.
  • ~94% of patients reported the use of vaping within a week of symptom onset.
presenting symptoms
  • Severity varies from patients who may have unimpressive symptoms to patients requiring intubation and ECMO.  Initial case series will inevitably focus on the more severe end of the spectrum (as these cases are more easily detected).  Over time, milder cases will likely be appreciated as well.
  • Acuity
    • Onset is usually subacute, with deterioration over a period of days (the median duration of symptoms prior to hospitalization was 6 days).
    • About a third of patients are initially diagnosed with a mild pneumonia and discharged home with oral antibiotic (e.g. azithromycin).
  • Presenting symptoms (Layden 2019):
    • 98% have respiratory symptoms (dyspnea in 87%; chest pain in 55%; cough in 83%; hemoptysis in 11%)
    • 81% had gastrointestinal symptoms (nausea in 70%; vomiting in 66%; diarrhea in 43%; abdominal pain in 43%).  These may initially be a predominant feature of the illness.
    • 100% of patients had some constitutional symptom (fever in 81%; chills in 58%; weight loss in 25%; fatigue/malaise in 45%)
    • 40% had headache.
    • Upper respiratory symptoms (e.g. rhinorrhea, sneezing, or congestion) don't seem to be a component of the illness.
presenting examination
  • Temperature >38C was present in 29% of patients.
  • Room air oxygen saturation was normal in one third, between 89-94% in a third, and <88% in a third of patients (Layden 2019).
radiographic features

  • Chest X-ray will generally show bilateral infiltrates (~90% of cases), although these may be absent early in the disease course.
  • CT scanning invariably shows bilateral ground-glass opacities.  Sub-pleural sparing may also be seen in more “typical” cases.
  • However, various patterns may be seen.  Additional findings which have been noted include pleural effusions, pneumomediastinum, and tree-in-bud opacities.
laboratory results 
  • CBC:
    • WBC count was >11,999/mm3 in 87% of patients.  The median WBC count was 16,000 with an interquartile range of 12,000-18,000 (Layden 2019)
    • Differential cell count revealed >80% neutrophils in 94% of patients.
    • No patient had greater than ~2% peripheral eosinophils (Layden 2019).
  • Acute phase reactants
    • Erythrocyte sedimentation rate (ESR) of >30 mm/hr was seen in 93% of patients.  This may be severely elevated (>100 mm/hr), which may incorrectly raise concern for vasculitis.
    • C-Reactive Protein (CRP) is often elevated in a range of 20-30 mg/dL (Maddock 2019)
    • Procalcitonin was a median of 0.58 ug/L (with an interquartile range of 0.35-1)(Layden 2019).
  • Brochoalveolar lavage results:
    • Often neutrophilic predominance (with a median of 65% neutrophils).
    • Eosinophilia isn't generally a feature (median 0% eosinophils, interquartile range 0-6%)
    • Lipid-laden macrophages are often seen on Oil Red-O stain, but not in all cases (Layden 2019).
case definition & diagnostic process
  • The current case definition is shown above.
  • VAPI is a diagnosis of exclusion (particularly the exclusion of infection).  Most affected patients are young with few other medical problems, which makes this a bit more straightforward.
  • Bronchoscopy is not necessary in all cases:
    • Only 45% of the patients in the Layden 2019 series received bronchoscopy.
    • The primary role of bronchoscopy is to exclude alternative diagnoses.  In patients with typical imaging features and no competing diagnosis, bronchoscopy may not be needed.
    • In patients with atypical imaging features (e.g. cavitation) or immunocompromise, bronchoscopy would be more important.  Clinical features concerning for an alternative diagnosis would also increase the importance of bronchoscopy (e.g. possible vasculitis involving the skin or kidneys).
    • Decisions regarding bronchoscopy may also be colored by how well the patient would likely tolerate this procedure.
therapy & course
  • Empiric antibiotics are often provided initially, until pneumonia may be excluded.
  • Steroids are usually given.
    • Many reports suggest that this is beneficial (although there is obviously no solid proof that steroid causes benefit).
    • The ideal dose of steroid is unclear.  ~ 1 mg/kg methylprednisolone daily generally seems reasonable, although some authors have reported using doses as high as 500 mg methylprednisolone daily (Maddock 2019; Davidson 2019)
  • Intubation may be required in about a third of cases (Layden 2019).
  • A few deaths have been reported, but the overwhelming majority of patients will recover.  Improvement often occurs over a period of days.
pathophysiology and cause ??
  • The prevalent theory is that most cases represent lipoid pneumonia, possibly related to vaping of cannabis oils.  However, numerous questions remain regarding the exact agent or agent(s) involved.  Furthermore, it is unclear whether all patients have the same exact pathology or (more likely) whether there may be some range of different pathophysiologic processes involved (e.g. most patients may have lipoid pneumonia, while some could have other pathologies such as cryptogenic organizing pneumonia).
  • Vitamin E has recently been used as a liquid carrier of tetrahydrocannabinol in some forms of vape.  Currently this appears to be the most likely culprit chemical.  Epidemiologic data shows a spike in cases beginning in June 2019, which could potentially coincide with the timepoint at which a specific chemical entered the vape market (Layden 2019).  This remains to be clarified further.

general evidence on VAPI

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The remainder of this chapter will discuss VAPI in general (based on data available prior to the current epidemic).

Published evidence consists of case reports, which are summarized below.  Although the literature includes only about two dozen case reports, the actual number of cases is probably considerably larger.  I've seen one patient with probable VAPI, but didn't submit it for publication (once several cases have been published, there's little impetus to publish additional case reports).  With an increasing recognition of this phenomenon and a rising popularity of vaping, the number of diagnosed cases will increase.

Overall, vaping seems to be capable of causing a variety of injury patterns in the lung.  This reflects the large number of different chemicals involved, which may have variable pathologic effects.  Cases may be roughly grouped based on the predominant pathological finding (table below).  However, in some cases there may be multiple simultaneous injury patterns (e.g. combined features of acute eosinophilic pneumonia and lipoid pneumonia).

This evidence is obviously very incomplete.  The omnipresent challenge to resuscitationists is to manage patients on the basis of incomplete information.  Please employ information in this chapter cautiously, with the recognition that this is a rapidly evolving topic.

The probable role of publication bias bears specific mention here.  Published cases are probably more dramatic and more thoroughly investigated than unpublished cases.  For example, a patient with moderate VAPI who improves with steroid and doesn't undergo bronchoscopy is unlikely to merit publication.  Thus, it's probable that published cases may over-estimate the severity of VAPI.

clinical presentation

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VAPI will often masquerade as pneumonia.  However, pleuritic chest pain may also raise concerns for acute pulmonary embolism.  Occasional patients may present with hemoptysis as a primary complaint.

core clinical features
  • Dyspnea
  • Hypoxemia
  • Vaping history (often with a recent initiation, increased frequency, or different product)
additional features which may be seen
  • Cough (may be productive, possibly with hemoptysis)
  • Pleuritic chest pain
  • Fever
  • Night sweats and weight loss

laboratory evaluation

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Laboratory evaluation is useful primarily to exclude other possible disorders.

typical results may include:
  • Complete blood count may show leukocytosis (up to ~40,000), generally with a neutrophilic predominance.
    • Eosinophilia is generally absent on admission – even in patients with acute eosinophilic pneumonia.
  • Erythrocyte sedimentation rate is usually normal in published cases, but can be elevated (see tweet below by Dr. Aberegg).
  • C-reactive protein (CRP) may be moderately elevated (e.g. 10-40 mg/dL).

radiographic evaluation

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chest X-ray
  • Should show bilateral infiltrates.
  • Infiltrates typically reflect alveolar filling (“fluffy,” poorly-defined infiltrates).  However, reticular infiltrates are also possible.
  • Chest x-ray is useful as a screening test, but it doesn't provide definitive characterization of infiltrates.
CT scan – basic characteristics of VAPI
  • Core features
    • Bilateral, ground-glass opacities
  • Features which shouldn't be seen (if present, may argue against VAPI)
    • Dense lobar consolidation
    • Dense nodules
    • Cavitation or necrosis of lung tissue

Some specific types of VAPI may be associated with signature findings on chest CT scan.  Although this isn't reliable, it may serve as a useful clue.  

VAPI with an acute eosinophilic pneumonia predominant pattern
  • Bilateral, ground-glass opacities.
  • Smooth septal thickening is often seen.
  • Pleural effusion(s) may be seen.
VAPI with an organizing pneumonia predominant pattern
  • Bilateral, ground-glass opacities.
  • Organizing pneumonia can generate diverse findings on CT chest, which makes it challenging to define a stereotypical pattern.  The following patterns have been reported:
    • (a) Sparing of the lung periphery (this pattern may be seen with various types of inhalation lung injury).
    • (b) Multiple ground-glass nodules distributed in a centrilobular pattern.
VAPI with lipoid pneumonia predominant pattern
  • Bilateral, ground-glass opacities.
  • Crazy-paving may be seen.  This refers to patchy involvement of some lobules, which are adjacent to un-affected lobules.  Septal thickening may accentuate the borders between normal lobules and diseased lobules.
VAPI with lipoid pneumonia causing a crazy-paving pattern, from McCauley et al.

bronchoscopy?

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The main role of bronchoscopy is to exclude infection.  Bronchoscopy can help diagnose various forms of VAPI (e.g. acute eosinophilic pneumonia or lipoid pneumonia).  However, this generally won't affect clinical management, because all forms of VAPI are treated with supportive care and steroid.

Most patients with suspected VAPI probably don't require bronchoscopy.  Potential indications for bronchoscopy might include the following:

  • Significant immunocompromise.
  • Clinical features (e.g. CT scan findings or exposure history) suggest the possibility of unusual infectious diseases, such as fungal pneumonia.
  • Patient is intubated for another reason (bronchoscopy may be increasingly easy and safe in this context).

diagnostic/therapeutic pathway

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Below is a potential approach to VAPI.  Most of these patients are young and previously healthy, which makes evaluation and treatment more straightforward.

VAPI is a diagnosis of exclusion.  Therefore, due diligence should always be invested to consider alternative diagnostic possibilities.  However, an invasive workup is often not necessary.  In younger patients without other medical problems, the differential diagnosis will generally boil down to pneumonia vs. VAPI.  A reasonable approach is empiric therapy with antibiotic and steroid (especially given that steroid is often beneficial for community acquired pneumonia anyway).

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

  • Failure to obtain a history regarding vaping and to consider this as a potential cause of respiratory failure.  Ideally this history should also include whether the patient is adulterating their own vaping liquid (which might increase the risk of VAPI).
  • The assumption that every patient with possible vaping-induced pulmonary injury requires an invasive evaluation (bronchoscopy and potentially surgical lung biopsy).

References

  • Agustin M, Yamamoto M, Cabrera F, Eusebio R. Diffuse Alveolar Hemorrhage Induced by Vaping. Case Rep Pulmonol. 2018 Jun 7;2018:9724530. doi: 10.1155/2018/9724530. PubMed PMID: 29984031; PubMed Central PMCID: PMC6011163.
  • Aokage T, Tsukahara K, Fukuda Y, Tokioka F, Taniguchi A, Naito H, Nakao A. Heat-not-burn cigarettes induce fulminant acute eosinophilic pneumonia requiring extracorporeal membrane oxygenation. Respir Med Case Rep. 2018 Dec 4;26:87-90. doi: 10.1016/j.rmcr.2018.12.002. PubMed PMID: 30560050; PubMed Central PMCID: PMC6288977.
  • Arter ZL, Wiggins A, Hudspath C, Kisling A, Hostler DC, Hostler JM. Acute eosinophilic pneumonia following electronic cigarette use. Respir Med Case Rep. 2019 Mar 18;27:100825. doi: 10.1016/j.rmcr.2019.100825. PubMed PMID: 30963023; PubMed Central PMCID: PMC6434163.
  • Atkins, G. and F. Drescher, Acute Inhalational Lung Injury Related to the Use of Electronic Nicotine Delivery System (ENDS). Chest, 2015. 148(4, Supplement): p. 83A.
  • Davidson K et al.  Outbreak of electronic-cigarette-assocciated acute lipoid pneumonia – North Carolina, July-August 2019.  MMWR Volume 68, E-publication ahead of print.
  • He T, Oks M, Esposito M, Steinberg H, Makaryus M. “Tree-in-Bloom”: Severe Acute Lung Injury Induced by Vaping Cannabis Oil. Ann Am Thorac Soc. 2017 Mar;14(3):468-470. doi: 10.1513/AnnalsATS.201612-974LE. PubMed PMID: 28248584.
  • Henry TS et al.  Imaging of Vaping-Associated Lung Disease.  NEJM 2019, E-publication pending print.
  • Itoh M, Aoshiba K, Herai Y, Nakamura H, Takemura T. Lung injury associated with electronic cigarettes inhalation diagnosed by transbronchial lung biopsy. Respirol Case Rep. 2017 Nov 17;6(1):e00282. doi: 10.1002/rcr2.282. PubMed PMID: 29321926; PubMed Central PMCID: PMC5757588.
  • Kamada T, Yamashita Y, Tomioka H. Acute eosinophilic pneumonia following heat-not-burn cigarette smoking. Respirol Case Rep. 2016 Oct 3;4(6):e00190. doi: 10.1002/rcr2.190. PubMed PMID: 28031826; PubMed Central PMCID: PMC5167280.
  • Khan MS, Khateeb F, Akhtar J, Khan Z, Lal A, Kholodovych V, Hammersley J. Organizing pneumonia related to electronic cigarette use: A case report and review of literature. Clin Respir J. 2018 Mar;12(3):1295-1299. doi: 10.1111/crj.12775. Epub 2018 Feb 22. PubMed PMID: 29392888.
  • Layden JE et al.  Pulmonary illness related to E-cigarette use in Illinois and Wisconsin – Preliminary report.  NEJM  September 2019; E-publication ahead of print.
  • Long, J.L., et al., Diffuse Alveolar Hemorrhage Due to Electronic Cigarette Use, in A54. CRITICAL CARE CASE REPORTS: ACUTE HYPOXEMIC RESPIRATORY FAILURE/ARDS. 2016, American Thoracic Society. p. A1862-A1862.
  • Maddock SD et al.  Pulmonary lipid-laden macrophages and vaping.  NEJM September 2019; E-publication ahead of print.
  • Mantilla, R.D., R.T. Darnell, and U. Sofi, Vapor Lung: Bronchiolitis Obliterans Organizing Pneumonia (BOOP) in Patient with E-Cigarette Use, in D22. REDUCING HARMS OF TOBACCO USE. 2016, American Thoracic Society. p. A6513-A6513.
  • McCauley L, Markin C, Hosmer D. An unexpected consequence of electronic cigarette use. Chest. 2012 Apr;141(4):1110-1113. doi: 10.1378/chest.11-1334. PubMed PMID: 22474155.
  • Modi, S., R. Sangani, and A. Alhajhusain, Acute Lipoid Pneumonia Secondary to E-Cigarettes Use: An Unlikely Replacement for Cigarettes. Chest, 2015. 148(4, Supplement): p. 382A.
  • Sommerfeld CG, Weiner DJ, Nowalk A, Larkin A. Hypersensitivity Pneumonitis and Acute Respiratory Distress Syndrome From E-Cigarette Use. Pediatrics. 2018 Jun;141(6):e20163927. doi: 10.1542/peds.2016-3927. Epub 2018 May 17. PubMed PMID: 29773665.
  • Thota D, Latham E. Case report of electronic cigarettes possibly associated with eosinophilic pneumonitis in a previously healthy active-duty sailor. J Emerg Med. 2014 Jul;47(1):15-7. doi: 10.1016/j.jemermed.2013.09.034. Epub 2014 Jan 21. PubMed PMID: 24462024.
  • Viswam D, Trotter S, Burge PS, Walters GI. Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes. BMJ Case Rep. 2018 Jul 6;2018:bcr2018224350. doi: 10.1136/bcr-2018-224350. PubMed PMID: 29982176; PubMed Central PMCID: PMC6040540.

The Internet Book of Critical Care is an online textbook written by Josh Farkas (@PulmCrit), an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.


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