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Image from the Centers for Disease Control and Prevention (CDC).

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Over the past decade, electronic cigarettes (e-cigarettes), also known as "e-cigs" and "vapes,"[1] have surged in popularity in the United States.[2] These devices may or may not contain nicotine and typically have less irritants than traditional tobacco products. They are often marketed with flavored e-liquids,[1] which are appealing to younger customers.

Although e-cigarettes have been promoted as a safer alternative to traditional cigarettes, the evidence supporting their use for smoking cessation remains modest.[3] More recent studies have documented the pulmonary toxicity of e-cigarette vapors, which are generally composed of aerosolized nicotine, flavored liquids, other additives, chemicals, heavy metals, and/or volatile organic compounds.[1,4] In fact, use of these devices has been linked to the phenomenon of "e-cigarette or vaping product use-associated lung injury" (EVALI).[5]

An outbreak of EVALI across the United States in the summer-early fall of 2019 prompted the CDC to monitor this condition.[6,7] For example, between April and October 2019, 89% of Utah patients with EVALI were hospitalized, 44% required admission to the intensive care unit (ICU), and 25% were diagnosed with acute respiratory distress syndrome (ARDS).[8]

Image from Flickr | Sarah Johnson (CC by 2.0), www.blacknote.com.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

A 15-year-old female patient presents to your clinic in the summer before her second year of high school with a chief complaint of persistent cough. Her mother accompanies her and expresses concern that her daughter was seen using an e-cigarette in class by her teacher. When asked, the patient says that she was only holding a USB flash drive.

What is the estimated prevalence of e-cigarette use in US high schools?

  1. 1 in 2
  2. 1 in 4
  3. 1 in 20
  4. 1 in 50
  5. 1 in 100
Image from the CDC.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Answer: B. 1 in 4

E-cigarette or vaporizer use has become increasingly common in youth, due to reasons such as high nicotine content, availability of a variety of flavors, and ability for discreet use, given that newer vaporizers can mimic writing tools ("vape pens") and USB flash drives.[9] A 2019 youth survey found that approximately 27.5% of high school students endorsed smoking e-cigarettes.[10] Among middle school students, the prevalence is also rising, with about 4.9% of students reporting e-cigarette use in 2018.[11]

The 2014-2018 National Health Interview Surveys (NHIS) found a disproportionate association between those aged 18-24 years and high daily use of e-cigarettes.[12] By comparison, about 2.8% of US adults use these products.[13]

Image from the CDC.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

After some encouragement, your patient admits to e-cigarette use. She says she smokes during recess and buys e-liquid pods online, choosing those without nicotine. Her favorite flavors are "Electric Lemon" and "Purple Cotton Candy Surprise." She mentions her friends have assured her that "Vaping is not bad for you like smoking."

What is the best next step in management of this patient?

  1. Reassurance
  2. Urine toxicology
  3. Smoking cessation counseling
  4. Contacting child protective services
  5. Referral to pulmonology services
Image from Smokefree Teen, National Cancer Institute (NCI).

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Answer: C. Smoking cessation counseling

Data exist to suggest e-cigarettes may constitute a safer alternative to traditional tobacco products; however, there are currently no longitudinal studies of long-term risks associated with e-cigarette use (eg, cancer risk).[14] Indeed, in a study of 12 brands of e-cigarettes, at least 40 toxic compounds and carcinogens were identified.[15] Moreover, heterogeneity remains in the levels of nicotine exposure via aerosolization in these products.[16] Just 15 puffs may deliver between 0.5 and 15.4 mg of nicotine, with the higher range far greater than that of a conventional cigarette.[16]

E-cigarette use has been linked to cardiotoxicity, periodontal disease, pulmonary dysfunction, and bladder cancer.[17-19] Heating of propylene glycol and glycerol products may also release formaldehyde, a known carcinogen.[20] Thus, non-nicotine vaping products can also produce toxic chemicals, including carcinogens such as formaldehyde. EVALI is an acute complication of e-cigarette use due to direct pulmonary parenchymal inflammation from exposure to irritants in the inhaled vapor.[21]

After discussing the potential risks associated with e-cigarette use with your patient, she agrees that this habit could harm her and assures her mother that she no longer wants to vape.

Table from the authors.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

In September, your now 16-year-old patient and her mother visit your clinic again. The teen complains of shortness of breath as well as chest pain, abdominal pain, and fever. The abdominal pain was present when she woke up this morning to go to school. After gym class, she felt out of breath and requested returning home.

You ask her if she still vapes. She admits that she never stopped using e-cigarettes and still smokes with friends after school. You order a chest radiograph; the findings are nondiagnostic.

What is the next step in your evaluation of this patient?

  1. Echocardiography
  2. Pulmonary lavage
  3. Pulmonary function testing
  4. Computed tomography (CT) scanning
  5. Magnetic resonance imaging (MRI)
Image from Adapa S, Gayam V, Konala VM, et al. J Investig Med High Impact Case Rep. 2020;8:2324709620947267. [Open access.] PMID: 32755249; PMCID: PMC7543135.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Answer: D. Computed tomography (CT) scanning

This patient has an extensive history of daily e-cigarette use. The CDC recommends obtaining a chest x-ray for all patients with a history of e-cigarette use accompanied by respiratory or gastrointestinal symptoms, especially those with an oxygen saturation below 95%[23] (as in the case of this patient). The most common radiographic findings are ground-glass opacities and infiltrates.[24] However, note that not all patients exhibit signs of EVALI on x-rays.[23]

The patient's chest x-ray was nondiagnostic. If an x-ray does not correlate with clinical findings, obtaining a CT scan is the next step in the clinical evaluation. Ground-glass opacities are the most frequent CT finding in individuals with EVALI (shown).[25]

Table from the authors.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Your patient has confirmed ground-glass opacities on CT scan. After a negative infectious workup, you diagnose her with EVALI on the basis of her history and clinical correlates. Her mother asks whether her daughter will be admitted to the hospital or if she will be able to go home today.

What aspect of this patient's clinical presentation should make you consider hospital admission?

  1. O2 saturation
  2. Fever
  3. Erythrocyte sedimentation rate
  4. Leukocytosis
  5. Blood pressure
Image from the CDC.[22]

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Answer: A. O2 saturation

The CDC recommends strongly considering admitting patients based on an oxygen saturation below 95%, respiratory distress, or select comorbidities.[22] In a 2019 study, the majority of patients with EVALI required hospitalization for respiratory failure, with a median hospital stay of 7 days.[26] Patients with EVALI who have less severe clinical features may be treated on an outpatient basis.[22]

The CDC provides an interim guidance for managing EVALI patients here, as well as an EVALI management algorithm here.

Image from Pexels | Gustavo Fring.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

On the basis of your patient's age, lack of comorbidities, and past medical history, you decide to manage her on an outpatient basis.

What pharmacologic treatment do you administer for EVALI?

  1. Remdesivir
  2. Oseltamivir
  3. Naloxone
  4. Bupropion
  5. Methylprednisolone
  6. Varenicline
Image from Jatlaoui TC, Wiltz JL, Kabbani S, et al. MMWR Morb Mortal Wkly Rep. 2019;68(46):1081-6. [Open access.] PMID: 31751322; PMCID: PMC6871902. CAP = community-acquired pneumonia; CXR = chest x-ray; EVALI = e-cigarette, or vaping, product use-associated lung injury.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Answer: E. Methylprednisolone

Patients diagnosed with EVALI should be given corticosteroid therapy.[22] However, keep in mind that lung injury secondary to e-cigarette use has a high degree of overlap with other lung diseases, particularly those with infectious causes.[27] Therefore, it is necessary to rule out infection and cardiopulmonary dysfunction prior to initiation of corticosteroid therapy.[26] Antibiotics for CAP and antiviral therapy for potential influenza may be considered.[22]

The CDC recommends that patients not admitted to the hospital return for follow-up in 1-2 days.[22]

Image from Wikimedia Commons | Librepath.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

To better understand the pathogenesis of EVALI, your institution conducts a clinical study of bronchoalveolar washings to identify substances that may contribute to lung injury in affected patients. The image shows alveolar macrophages sampled from bronchoalveolar fluid.

Which of the following is a vaping product additive that has been shown to be increased in the bronchoalveolar washings of e-cigarette users?

  1. Vitamin E acetate
  2. Petroleum distillates
  3. Terpenes
  4. Medium-chain triglyceride oils
Left: A laboratory technician pipettes a sample of vitamin E acetate. Top right: Various e-cigarettes undergoing testing. Both images from the CDC | Lauren Bishop.

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

Answer: A. Vitamin E acetate

Vitamin E acetate has been detected in the bronchoalveolar lavage fluid of patients diagnosed with EVALI.[28] Although vitamin E is generally not considered harmful if consumed in foods or applied topically as a cosmetic agent, it may be toxic if inhaled.[7]

In addition to the association between vitamin E acetate and EVALI, numerous toxic substances are under investigation as potential contributors to cases. Other toxic compounds include nicotine, benzene, toluene, carbonyls, trace metals, bacterial endotoxins, and fungal glycans, among others.[29]

Image from the CDC.[7]

E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI): A Case Study

Arif Musa, MS; Elizabeth Warbasse, BA; Lawrence H Warbasse III, MD, FACP | October 26, 2020 | Contributor Information

The CDC does not recommend the use of e-cigarettes or other vaping products.[1,7]

Clinicians should be aware that EVALI remains a diagnosis of exclusion, requiring extensive workup prior to diagnosis. There remains considerable overlap between symptoms associated with EVALI and infectious diseases, including influenza and coronavirus disease 2019 (COVID-19).[30]

Although cases of EVALI have been on the decline since the 2019 summer-early fall outbreak (shown), the CDC and US Food and Drug Administration (FDA) do not recommend informal sharing of e-cigarettes or vaping products, suggest continuous monitoring of outbreak-related symptoms when using such products, and firmly recommend against the use of these devices by groups that may be at increased risk of EVALI, such as youths, young adults, and pregnant women.[1,7]

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