Electrotonic-Cigarette or Vaping Product Use Associated Lung Injury: Diagnosis of Exclusion

Ali A. Mahdi MD, Chris Allahverdian MD, Sharareh Shahangian MD

Dignity Health, St Mary Medical Center, Department of Internal Medicine, Long Beach, California 90813, USA

Abstract

The first reports of lung injury attributable to vaping date back to 2012, but the ongoing outbreak of electrotonic-cigarette or vaping product use associated lung injury (EVALI) began in 2019. It is a diagnosis of exclusion. In this case report, we describe a patient with history of excessive vaping for the last 3 weeks who was admitted to the intensive care unit for acute hypoxic respiratory failure. The patient was diagnosed with EVALI given the history of vaping in the setting of negative infectious work-up and radiographic imaging that showed lung opacities.

Case Presentation 

A 37-year-old man with no significant past medical history initially presented to the emergency department (ED) with “chest pain and trouble breathing.” He reported first feeling chest pain localized to the substernal region 5 days prior to presentation; described it as pleuritic in nature; and rated intensity as severe. The patient stated deep breaths and laying flat aggravated his pain, while leaning forward relieved it. He also reported associated subjective fevers, non-productive cough, nausea and diarrhea but denied any lower extremity swelling, calf pain, prolonged immobilization, or history of congestive heart failure (CHF) or venous thromboembolism (VTE).

The patient denied any past medical or surgical history and reported not being on any medications or over-the-counter supplements. He denied any medication, diet, or environmental allergies. He lives in an apartment (built in the 1990s) with his wife, and does not have any pets. Patient works full-time at a box manufacturing facility where he processes shipping labels, reports drinking approximately 5 to 6 beers a day, denies any history of illicit drug use. He smoked one pack per day for the past ten years, but reported to have quit smoking over the last month. 

Due to his significantly worsening shortness of breath and severe chest pain, he was prompted to present to the ED. Upon presentation, he was febrile (38.9 degrees Celsius), hypoxic (saturating at 88%) in the setting of tachypneic (22 breaths per minute), tachycardic (117 beats per minute), and normotensive (systolic of 105 mmHg). Patient was started on supplemental oxygen, 4 Liters (L) nasal cannula (NC), yet had been noted to continue to desaturate in the mid-80's. Despite being transitioned to 11L non-rebreather mask, he remained tachypneic and hypoxic, and was subsequently started on high flow nasal cannula (HFNC), 50L at 0.50 fraction of inspired oxygen (FiO2).

Physical examination was significant for a man who appeared about the stated age in respiratory distress. He was noted to have scleral icterus, yellow skin discoloration, supraclavicular retraction, increased respiratory exertion, and fine bibasilar crackles. S1 & S2 were heard but no additional heart sounds or friction rubs were noted. His abdomen was soft, nondistended, nontender to superficial or deep palpation, without organomegaly, but with normal bowel sounds. No superficial venous dilation or telangiectasia was noted. Upper and lower extremities were without edema or tenderness. Homan’s sign was negative.

Initial laboratory investigations were significant for leukocytosis (white blood cell count of 12.6 K/uL), normocytic anemia (hemoglobin 8.2 g/dl) with an INR of 1.25, D-dimer 415 ng/ml DDU, troponin 0 ng/ml, hyponatremia (serum sodium 130 mmol/L), potassium 3.8 mmol/L, creatinine 0.79 mg/dL, BUN of 7mg/dL, alanine transaminase 21 IU/L, aspartate transaminase 63 IU/L, alkaline phosphatase 178 IU/L, gamma-glutamine transaminase 224 IU/L, total bilirubin 6.9 mg/dL (direct bilirubin 5.9 mg/dL). His lactic acid was elevated at 3.76 mEq/L. SARS-CoV-2 polymerase chain reaction (PCR) nasal swab was negative. Urine analysis was positive for moderate bilirubin. Urine toxicology was negative. 

Arterial blood gas while on HFNC showed pH 7.45, pCO2 27 mmHg, pO2 68 mmHg and HCO3 21 mEq/L. His PaO2:FiO2 was calculated to be 136, significant for moderate acute respiratory distress syndrome (ARDS).

Electrocardiogram (ECG) showed normal sinus rhythm, rate of 99 beats per minute, no ST segment changes or T wave inversions, without axis devious or conduction abnormalities.

Chest X-Ray (CXR) was significant for extensive patchy bilateral multifocal patchy infiltrates in the mid and lower lobes. Computer tomography (CT) of the chest without contrast (Figure 1) was significant for severe multifocal pneumonia with small bilateral pleural effusions.

Figure 1. Representative images from the computer tomography (CT) of the chest without contrast in (A) lung windows and (B) soft tissue widows. The CT was significant for severe multifocal pneumonia with small bilateral pleural effusions.

CT of the abdomen and pelvis with contrast was significant for hepatomegaly with diffuse fatty infiltrated, moderate gallbladder distention without intra or extra hepatic duct dilatation non-concerning for obstruction. Ultrasound (US) of the gallbladder revealed a distended gallbladder without evidence of stone or wall thickening, but was significant for sludge.

The patient was admitted to the intensive care unit (ICU) with severe sepsis and acute hypoxic respiratory failure likely secondary to presumed viral versus bacterial community acquired pneumonia (CAP) requiring HFNC. Blood cultures were collected, and the patient was started on fluid resuscitation and broad-spectrum antibiotics. Sputum cultures, respiratory viral panel, atypical pneumonia serologies and urine for legionella and pneumococcal antigens were ordered.

His Well’s score was calculated at 1.5 placing him at a low risk for pulmonary embolism (PE) with a D-dimer of 415 ng/ml DDU, likely secondary to septic-inflammatory state. However, given his continued high oxygen requirement, saturating in the high-80s to the low-90s while on HFNC 50L of 60% FiO2, and increased respiratory effort, chest CT chest angiography was ordered but negative for PE or acute aortic pathology. Transthoracic echocardiogram (TTE) demonstrates a preserved left ventricular function with an ejection fraction of 60%, without valvular disease or pericardial effusion.

Repeat CXR showed worsening diffuse multifocal infiltrates concerning for progressive ARDS. He was started on a 5-day course of systemic steroids (dexamethasone) given his worsening oxygen requirements and CXR findings. SARS-CoV2 nasal PCR was repeated as well, which remained negative. Cryptococcus, coccidiomycosis & QuantiFERON-Gold were ordered. His oxygen requirements improved. Labs revealed normalization of lactic acid and bilirubin with down-trending liver enzymes with correlating resolution of patient’s jaundice and icterus. He also reported significant improvement in his gastrointestinal symptoms. Subsequently, he was transferred from the ICU to the telemetry unit.

Infectious work-up (including Streptococcus pneumonia, chlamydia psittaci, chlamydia pneumonia, mycoplasma pneumonia, Legionella pneumonia, cryptococcus, aspergillosis, cryptococcus, histoplasmosis, human immunodeficiency virus, Pneumocystis jiroveci pneumonia (PCP), and tuberculosis), respiratory viral panel and cultures were all negative. Of note, the patient's wife reported that over the course of the last few weeks, the patient had started vaping e-cigarettes. Upon discussion, he that he started vaping a nicotine-containing product in order to quit smoking cigarettes 3-weeks ago, states that he has been “excessive vaping for the last 2-3 weeks.”

Given newfound history of vaping in the setting of negative infectious work-up and CT imaging that showed dense ground glass opacities throughout, differential diagnosis now included E-cigarette, or vaping product, use associated lung injury (EVALI) versus respiratory bronchiolitis associated interstitial lung disease (RB-ILD) secondary to smoking. He was treated with high dose systemic steroids (methylprednisolone) and PCP prophylaxis with trimethoprim-sulfamethoxazole. The broad-spectrum antibiotics were discontinued.

He started to demonstrate significant improvement in his oxygen requirement and in his clinical symptoms, was no longer coughing and was able to ambulate without dyspnea. Repeat CT scan demonstrated interval improvement in pulmonary infiltrates, although radiographic findings on CT were still significant for diffuse pulmonary infiltrates. The patient had near-complete resolution of symptoms, was titrated down to 2L NC, was transitioned to room air, and discharged on hospital day 21 on a steroid taper and PCP prophylaxis.

Discussion 

The first reports of lung injury attributable to vaping date back to 2012, but the ongoing outbreak of electrotonic-cigarette or vaping product use associated lung injury (EVALI) began in 2019 (1). By February 2020, the Center for Disease Control (CDC) documented over 2800 EVALI hospitalizations, amongst which 68 patients died (2). E-cigarettes function to aerosolize various chemicals (including nicotine, tetrahydrocannabinol, favoring and other additives) for inhalation (3). EVALI is a form of acute or subacute lung injury whose pathogenesis is unknown and is thought to be a spectrum of disease, rather than a single process (4,11). The histopathological patterns include acute fibrinous pneumonitis, diffuse alveolar damage and organizing pneumonia, more commonly bronchiolocentric with accompanying bronchiolitis (5). This spectrum of nonspecific acute lung injury commonly presents with cough, dyspnea, gastrointestinal symptoms with accompanying constitutional symptoms (1).

Radiographic findings of EVALI demonstrate a spectrum of nonspecific acute lung injury patterns. Bilateral opacities are typically seen, the majority of chest radiographs demonstrate diffuse hazy or consolidative opacities (6). CT opacities are typically ground glass in density and may spare subpleural spaces. Pleural effusions are less common findings (7). Other radiographic patterns have been noted suggestive of one or more disease processes: diffuse alveolar damage (dependent consolidation, diffuse ground glass and air bronchograms), acute eosinophilic pneumonitis (centrilobular ground glass opacities in the anterior lung fields, confluent ground glass opacities in dependent areas and lobules of mosaic attenuation) and organizing pneumonia (diffuse, multifocal discrete and confluent) (7).

EVALI is a diagnosis of exclusion; thus, pulmonary infectious causes and other etiologies of progressive respiratory insufficiency should be excluded (7). Currently CDC criteria for a confirmed case of EVALI include: (1) Use of e-cigarette or related products in the last 90 days, (2) Lung opacities on CXR or CT, (3) Exclusion of lung infection, including negative influenza polymerase chain reaction (PCR) or rapid test (unless out of season), viral respiratory panel, and if clinically indicated, urine antigen tests for Legionella and Streptococcus pneumonia, blood & sputum cultures, bronchoalveolar lavage and HIV-related opportunistic infections, (4) absence of likely alternative diagnosis including cardiovascular disease, rheumatologic disease and neoplastic (2).

Supportive care initially focuses on management of hypoxia with supplemental oxygen at a goal saturation of 88 to 92% (3). Empiric antibiotics should also be initiated to cover likely pathogens for CAP. Although the optimal treatment of EVALI is not yet known, systemic glucocorticoids have been used in the majority of patients with varying efficacy (9). Given the postential efficacy and low incidence of adverse effects, systemic glucocorticoids should be considered in EVALI cases with progressively worsening symptoms and hypoxemia (7,10). Flexible bronchoscopy may be utilized in excluding other causes of non-resolving or progressive pneumonitis; however, bronchoscopy is generally reserved for patients with progressive or severe symptoms despite treatment.

Our patient’s initial complaint of chest pain upon presentation raised concerns for cardiovascular disease. ECG without any signs of acute ischemia in the setting of a troponin of 0.000 ng/ml was not indicative of acute coronary syndrome. Marginally elevated D-dimer in the setting of worsening hypoxemia and tachycardia was concerning for PE, but CTA was non-significant for any PE or aortic pathology. TTE without pericardial effusion and ECG without PR segment depression or ST segment elevations, ruled out pericarditis. The initial chest CT raised concerns for multifocal pneumonia; however, infectious, and autoimmune workup were negative. Given the patient's history of vaping within the last 90 days, diffuse dense ground glass opacities on CT, absence of infectious etiology and absence of alternative diagnosis, the patient met the CDC Criteria for EVALI and started on treatment. Given the patient's clinical improvement and reduced oxygen requirements while on systemic steroids, flexible bronchoscopy was deferred.

Conclusion

While alternative causes of respiratory illness may be more prevalent, it is important to consider and assess for pulmonary illness associated with vaping, particularly in patients where no other cause can be clearly identified. Patients reporting respiratory complaints as well as gastrointestinal symptoms should be questioned about any recent e-cigarette to assess for possible EVALI given the appropriate clinical scenario, radiographic findings, and absence of pulmonary infectious etiologies and other causes progressive respiratory insufficiency.

References

1. Jonas AM, Raj R. Vaping-Related Acute Parenchymal Lung Injury: A Systematic Review. Chest. 2020 Oct;158(4):1555-1565. [CrossRef] [PubMed]
2. Centers for Disease Control and Prevention (CDC). Outbreak of Lung Injury Associated with the Use of E-Cigarette, or Vaping, Products. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#latest-information (Accessed on May 06, 2020).
3. Schier JG, Meiman JG, Layden J, et al. Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use - Interim Guidance. MMWR Morb Mortal Wkly Rep. 2019 Sep 13;68(36):787-790. [CrossRef] [PubMed]
4. 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. [CrossRef] [PubMed]
5. Butt YM, Smith ML, Tazelaar HD, et al. Pathology of Vaping-Associated Lung Injury. N Engl J Med. 2019 Oct 31;381(18):1780-1781. [CrossRef] [PubMed]
6. Aberegg SK, Cirulis MM, Maddock SD, Freeman A, Keenan LM, Pirozzi CS, Raman SM, Schroeder J, Mann H, Callahan SJ. Clinical, Bronchoscopic, and Imaging Findings of e-Cigarette, or Vaping, Product Use-Associated Lung Injury Among Patients Treated at an Academic Medical Center. JAMA Netw Open. 2020 Nov 2;3(11):e2019176. [CrossRef] [PubMed]
7. Layden JE, Ghinai I, Pray I, et al. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report. N Engl J Med. 2020 Mar 5;382(10):903-916. [CrossRef] [PubMed]
8. Maddock SD, Cirulis MM, Callahan SJ, Keenan LM, Pirozzi CS, Raman SM, Aberegg SK. Pulmonary Lipid-Laden Macrophages and Vaping. N Engl J Med. 2019 Oct 10;381(15):1488-1489. [CrossRef] [PubMed]
9. Davidson K, Brancato A, Heetderks P, Mansour W, Matheis E, Nario M, Rajagopalan S, Underhill B, Wininger J, Fox D. Outbreak of Electronic-Cigarette-Associated Acute Lipoid Pneumonia - North Carolina, July-August 2019. MMWR Morb Mortal Wkly Rep. 2019 Sep 13;68(36):784-786. [CrossRef] [PubMed]
10. Josef V, Tu G. Case report: the importance of screening for EVALI. Southwest J Pulm Crit Care. 2020;20(3)87-94. [CrossRef]

Cite as: Mahdi AA, Allahverdian C, Shahangian S. Electrotonic-Cigarette or Vaping Product Use Associated Lung Injury: Diagnosis of Exclusion. Southwest J Pulm Crit Care Sleep. 2022;24:96-100. doi: https://doi.org/10.13175/swjpccs026-22 PDF 

A Case Series of Electronic or Vaping Induced Lung Injury

Ronald Ferrer Espinosa DO¹

Abdirahman Hussein MD²

Matthew Sehring DO¹

Mohamad Rachid MD¹

Ryan Dunn MD¹

Deepak Taneja MD¹

Department of Pulmonary and Critical Care Medicine¹

Department of Internal Medicine²

University of Illinois College of Medicine at Peoria

Peoria, Illinois 

Abstract

Introduction: Since their introduction, electronic cigarette use has increased and was even proposed as an alternative to traditional tobacco use. Recently, a series of patients with acute respiratory failure due electronic cigarette, or vaping, associated lung injury (EVALI) in 2019 has been described which has largely been attributed to tetrahydrocannabinol (THC) containing vaporizer itself, as well as vitamin E acetate. Several case series have been published regarding the acute presentation, diagnosis and management. In addition to diagnosis and management of EVALI, we sought to describe potential long-term effects of lung parenchyma in these patients.

Methods: A retrospective review was performed on 16 patients with clinically diagnosed EVALI at OSF St Francis Medical Center between August 01 2019 and February 1 2020. Relevant demographic and clinical data were collected in patients diagnosed with EVALI.

Results: Of the 16 patients in the study the median age (IQR) age was 25.25 (20-29) and 94% were male. The predominant presenting symptoms were dyspnea (94%), cough (56%), nausea 63%), vomiting (63%), abdominal pain (50%), diarrhea (50%), and fever (63%). 2 (13%) patients required endotracheal intubation. Common features of computerized tomography (CT) scan were bilateral diffuse ground glass opacity (93%), septal thickening (53%), and subpleural sparing (47%). Bronchoalveolar lavage (BAL) was obtained in 3 patients and all demonstrated neutrophil predominance of 69% (56-90). One BAL was significant for hemosiderin laden macrophages. Post hospital follow up pulmonary function tests were obtained in 3 and 2 of these were significant for obstructive lung disease.

Conclusions: In this case series of patients diagnosed with vaping associated lung injury, obstructive lung disease may be seen on pulmonary function testing and surveillance of these patients should occur regardless of duration.

Keywords: CT scan, EVALI, bronchoalveolar lavage, electronic cigarette, pulmonary function testing, respiratory failure, tetrahydrocannabinol, vaping, vaping associated lung injury, vitamin E,

Introduction

The first cases of vaping associated lung injury (EVALI) were reported in Wisconsin and Illinois in the summer of 2019 which reached its peak in the fall of 2019 (1). This sudden epidemic of respiratory failure in patients who used tetrahydrocannabinol (THC) containing vaporizing devices lead the Food and Drug Administration (FDA), Center for Disease Control (CDC) and local public health departments to initiate investigations and research into the causative mechanisms of this disease. Currently, it is postulated that vitamin E acetate plays a role in the pathogenesis of VALI, as this substance was found in samples of vaping cartridges and in the bronchoalveolar fluid of patients with the disease (2,3). These pathological pathways are still being elucidated. Little is known about the long-term damage to the respiratory system in patients with EVALI. In this study, we sought to describe the diagnostic commonalities in patients with EVALI and describe potential long-term complications.

Methods

The study was a retrospective cohort analysis. Institutional Review Board (IRB) approval (1593746-1) was obtained through the University of Illinois College of Medicine at Peoria IRB. Data was collected for consecutive patients over 18 years of age who were diagnosed with EVALI between the dates of August 1, 2019 and February 1, 2020. The diagnosis of EVALI was consistent with the outbreak case surveillance definition. A confirmed case required the following to satisfy criteria: e-cigarette or dabbing in 90 days before symptom onset, pulmonary infiltrate, absence of infection, and no evidence of alternative plausible causes. A presumptive case definition included the above definition except for possibility of another cause of the patient’s symptoms such as infection. Data were extracted from the electronic medical record. The recorded data included the following: age, gender, co-morbidities, tobacco and electronic cigarette use history, need for endotracheal intubation, symptoms on presentation to the emergency department, computerized tomography findings, pulmonary function test values, bronchoalveolar lavage fluid studies, and discharge treatment plans. Obstructive lung disease is based on the American Thoracic Society/European Respiratory Society criteria that recommends the fifth percentile of the distribution in a population of healthy lifelong nonsmokers as the lower limit of normal. One patient described in this study has been previously described (4). Continuous variables are presented at median and interquartile range (IQR) with 95% CI. Categorical variables are described as number of patients (percentage).

Results

From August 1, 2019 to February 1, 2020, a total of 16 patients with either confirmed or presumptive vaping associated lung injury were reviewed. Table 1 shows the demographic data obtained from these patients.

 

The median age was 25.25 (IQR, 20-29) and the majority of patients were male 94% (n=15). Only 13% (n=2) of patients had previously diagnosed lung conditions, both of which were asthma. Of the reported THC brands, Dank© was the most commonly reported occurring in 25% (n=4) of patients (Table 2).

However, 50% (n=8) of THC products were not clearly stated in the patient’s medical record. Tobacco cigarette and tobacco electronic cigarette use were also documented, occurring in 63% (n=10) and 44% (n=7) of patients, respectively. Of those reporting tobacco use, the median pack years was 1.5 (IQR, 0.5-4.25). 7 patients reported no prior tobacco use. 13% (n=2) of patients required endotracheal intubation
 

Patients' symptoms are summarized in Table 3.

Any respiratory symptom occurred in 94% (n=15) of patients which included dyspnea 94% (n=15), cough 56% (n=9), chest pain 25% (n=4), and hemoptysis 19% (n=3). Abdominal symptoms were common and occurred in 75% (n=12) of patients. The most common gastrointestinal symptom were both nausea and vomiting 63% (n=10). These were followed by abdominal pain and diarrhea 50% (n=8). Fever was the most common constitutional symptom occurring in 63% (n=10) of patients. Less common constitutional symptoms included fatigue and chills both of which occurred in 13% (n=2) of patients. 

Chest computerized tomography (CT) scans were available in 94% (n=15) of patients. The findings are summarized in Table 4.

The most common radiographic feature was bilateral diffuse ground glass opacity (GGO), which occurred in 93% (n=14) of patients. Septal thickening and subpleural sparing were the next most common radiographic findings, occurring in 53% (n=8) and 47% (n=7) patients, respectively. Less common features that were described on chest CT scan were centrilobular nodular consolidations occurring in 27% (n=4) and reverse haloing occurring in 7% (n=1, Figure 1).

Figure 1.  Reverse halo sign in a patient with EVALI.

Three patients diagnosed with EVALI underwent bronchoscopy with bronchoalveolar lavage which are summarized in table 5.

Bronchoscopy was performed when the outbreak case definition was not met or there was a clinical concern for a secondary pathological process. The “typical” bronchoalveolar lavage (BAL) differential was neutrophilic predominant (56%-90%) with elevated macrophage and/or monocyte counts (4-19%, 0-23%). The lymphocyte count was typically low (0-4%) as well as the eosinophil count (0-1%). All the microbiologic data from these lavage samples were negative and included the following tests: aerobic and anaerobic bacterial cultures, fungal cultures, silver stain, acid fast bacilli smear and culture, varicella zoster polymerase chain reaction (PCR), histoplasma antigen and galactomannan. The results of cytology were different in all three BAL samples and were significant fore alveolar macrophages, atypical glandular cells and hemosiderin laden macrophages. At the time of bronchoscopy, only 1 or 3 patients was on or received systemic steroids therapy.

A few complications occurred in our cohort which included pneumothorax, pneumorrhachis, pulmonary embolism and Takutsubo cardiomyopathy. The case of Takusubo cardiomyopathy has been reported in the literature (4). The rate of pneumothorax was 13% (n=2). The pneumorrhachis 6% (n=1) occurred in a patient with pneumothoraces. Pulmonary embolism was only seen in 1 patient.

The discharge treatment course involved mainly systemic corticosteroids which were given in 81% (n=13) of patients. Antibiotics were continued at discharge in a minority of patients 38% (n=6). The majority of patients (94%) recovered and were asymptomatic at a later clinic visit. One patient remained symptomatic with persistent dyspnea.

Full pulmonary function tests were obtained in 3 patients (Table 6).

The timing of the pulmonary function tests occurred 3-4 weeks post hospital discharge. THC vape duration for these patients ranged from 4-12 weeks and tobacco pack years ranged from 0-2. Forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratios were 70%, 71%, and 86%. FEV1% ranged from 70 to 119%. FVC ranged from 81% to 119%. The total lung capacity in these three patients ranged from 85% to 109%. Diffusing capacity of carbon monoxide (DLCO) ranged from 60% to 100%. The flow volume loops of two patients demonstrate coving of the expiratory limb (Figure 2).

Pre-EVALI pulmonary function testing was not available for review in any of the patients.

Discussion

In this case series of patients with vaping associated lung injury of 16 patients in Central Illinois from August 1 2019 through February 1, 2020 the majority were younger men with respiratory and gastrointestinal symptoms. The symptomatology was consistent with previously published data (1,5,6,7). The exact pathophysiologic mechanisms implicated in vaping associated lung injury are currently still under investigation, but vitamin E acetate has recently been implicated possibly through the transition of tocopherols induced transition of phosphatidiylcholines from gel to liquid crystalline, causing surfactant dysfunction (2). The same authors proposed an alternative mechanism whereby ketene, created while heating e-cigarette products, causes direct lung irritation. However, many branded vaping products are not commercially produced and the heterogenous ingredients such as propylene glycol and other flavoring ingredients in these products may reflect its informal creation, which may influence the development of different disease mechanisms, clinical phenotypes and imaging findings (8,9).

A growing body of EVALI cases demonstrate predominant features on computerized tomography which include basilar predominant centrilobular nodular ground glass opacities and ground glass opacities with subpleural sparing. An initial study proposed four imaging patterns which included acute eosinophilic pneumonia, diffuse alveolar damage, organizing pneumonia and lipoid pneumonia and predicted the dominant CT scan findings (10). Later in a small case series of pediatric patients, centrilobular ground glass opacities were present in 92% and ground glass opacities with subpleural sparing were present in 75% of patients (11). The importance of recognizing these patterns is essential, especially in the adolescent and young adult populations where disclosure of medical history may prove to be difficult. Our findings support the cases in literature, with 93% of patients having bilateral diffuse basilar predominant GGO (93%), some associated with subpleural sparing (47%) and to a lesser degree centrilobular nodular consolidation (27%).

The role of bronchoscopy in patients with vaping associated lung injury has waned with as the characterization of clinical and radiographic findings has matured. Importantly, there is no finding on bronchoscopy that is specific for diagnosis of EVALI. Recently, the role of bronchoscopy with bronchoalveolar lavage (BAL) has been suggested to be performed in cases with a high pretest probability of EVALI with atypical features that cannot be attributed to vaping (5).  Lipid laden macrophages (LLM) are a non-specific finding in many different illnesses such as infection, aspiration, drug reactions, lipoid pneumonia, pulmonary alveolar proteinosis and autoimmune disorders, but the absence of LLM, argued by Aberegg, would be an atypical finding in EVALI (5,12). Our BAL fluid differentials are consistent with the published data, with elevations in neutrophils and/or monocytes and macrophages, with scant lymphocytes and eosinophils. In our institution, staining for lipid laden macrophages was not routinely performed. However, in one of our cytologic BAL samples hemosiderin macrophages were identified. The inconsistent cytologic findings on BAL in our series supports the notion of heterogenous underlying pathophysiologic mechanisms involved in EVALI.

The long-term effects of EVALI on lung parenchyma are unknown. Prior studies evaluating the effects of electronic cigarette use prior to the EVALI epidemic have suggested airway hyper responsiveness and an obstructive pattern on spirometry. In mice, it has been previously demonstrated that aerosolized nicotine induced airway hyperreactivity (13). A human study of 30 electronic cigarette users with at least 6 months of use compared with matched controls, demonstrated PFTs consistent with peripheral obstruction (14). A different study comparing vaping asthmatics versus healthy controls demonstrated acute declines in the FEV1/FVC ratio (15). Additionally, a few recent reports of pulmonary function testing have been documented in patients diagnosed with EVALI in late 2019 and early 2020. One study of intubated adults reported one follow-up PFT that was significant for only a low DLCO (16). A case series of pediatric patients describes two patients with 6 week follow up PFT’s that were significant for obstructive lung disease, and one of these patients had a low DLCO (11). Our study contributes 3 full PFT’s in adult patients diagnosed with EVALI performed at either 3 or 4 weeks following hospital discharge. Two of these PFT’s demonstrated obstructive lung disease, of which one had a low DLCO. The duration of vaping in these two abnormal cases were 8 and 12 weeks, and the pack years of tobacco use were 2 and 1.25 years. This small data set suggests that patients who participate in electronic cigarette use, or vaping, may be at higher risk for developing obstructive lung disease regardless of the duration of use. It is also important to take into account that a fixed FEV1/FVC ratio may underestimate young patients with obstructive lung disease (17). Using the lower limit of normal in this younger patient population is likely to be more sensitive in detecting obstructive physiology. It is plausible that vaping may cause an accelerated obstructive lung pattern due to the many potential pathways for lung injury. Full pulmonary function testing in any patient who was diagnosed with EVALI or continues to use electronic cigarettes, or vaping, products should be considered.

This study has several limitations. First, this was a retrospective study of patients at a single center in one geographic location. Second, our sample size was relatively small. Third, our clinical follow up rate was only 50%, of which only 37% completed PFT’s.

Conclusions

In our case series of 16 patients, predominantly male, diagnosed with EVALI there was a high incidence of gastrointestinal symptoms on presentation and follow up pulmonary function tests suggested there may be an increased risk for obstructive lung disease. Avoidance of vaping products, especially “Dank” and other similarly formulated products, is strongly recommended.

References

1. Layden JE, Ghinai I, Pray I, et al. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report. N Engl J Med. 2020 Mar 5;382(10):903-916. [CrossRef] [PubMed] 
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13. Larcombe AN, Janka MA, Mullins BJ, Berry LJ, Bredin A, Franklin PJ. The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice. Am J Physiol Lung Cell Mol Physiol. 2017 Jul 1;313(1):L67-L79. [CrossRef] [PubMed]
14. Meo SA, Ansary MA, Barayan FR, Almusallam AS, Almehaid AM, Alarifi NS, Alsohaibani TA, Zia I. Electronic Cigarettes: Impact on Lung Function and Fractional Exhaled Nitric Oxide Among Healthy Adults. Am J Mens Health. 2019 Jan-Feb;13(1):1557988318806073. [CrossRef] [PubMed]
15. Kotoulas SC, Pataka A, Domvri K, et al. Acute effects of e-cigarette vaping on pulmonary function and airway inflammation in healthy individuals and in patients with asthma. Respirology. 2020 Oct;25(10):1037-1045. [CrossRef] [PubMed]
16. Choe J, Chen P, Falk JA, Nguyen L, Ng D, Parimon T, Ghandehari S. A Case Series of Vaping-Associated Lung Injury Requiring Mechanical Ventilation. Crit Care Explor. 2020 Jan 29;2(1):e0079. [CrossRef] [PubMed]
17. Cerveri I, Corsico AG, Accordini S, et al. Underestimation of airflow obstruction among young adults using FEV1/FVC <70% as a fixed cut-off: a longitudinal evaluation of clinical and functional outcomes. Thorax. 2008 Dec;63(12):1040-5. [CrossRef] [PubMed]

Cite as: Espinosa RF, Hussein A, Sehring M, Rachid M, Dunn R, Taneja D. A Case Series of Electronic or Vaping Induced Lung Injury. Southwest J Pulm Crit Care. 2021;23(2):62-9. doi: https://doi.org/10.13175/swjpcc032-21 PDF 

Case Report: The Importance of Screening for EVALI

Vanessa Josef MD, MS

George Tu, MD, FCCP

Department of Internal Medicine and Lung Center of Nevada

HCA MountainView Hospital

Las Vegas, Nevada, USA

Abstract

E-cigarette or vaping product use associated lung injury (EVALI) is an epidemic that has swept the United States by storm starting in Sept 2019. E-cigarettes or vaping was initially advertised as a “safer” alternative to smoking cigarettes when they entered the market in 2007. Only now are we are starting to see the complications of a not so harmless behavior. Many times, EVALI can present similar to community acquired pneumonia (CAP), which can cause a clinical conundrum when despite adequate antibiotic coverage, patients’ respiratory status tend to decline. Through our case report, we demonstrate and stress the importance of early screening for e-cigarette and vaping use in social history to increase clinical suspicion of EVALI and provide early intervention if a patient does not respond to CAP treatment, in hopes of identifying more cases of EVALI and igniting future research. 

Introduction

The recent outbreaks of E-cigarette or vaping product use associated lung injury (EVALI) in Sept 2019, has placed the spotlight on the dangers of vaping. EVALI is a form of acute or subacute lung injury whose pathogenesis is unknown and is thought to be a spectrum of disease, rather than a single process. It has many findings such as organizing pneumonia, diffuse alveolar damage or acute fibrinous pneumonitis that are bronchiocentric and accompanied by bronchiolitis (1). If not identified quickly, EVALI has led to non-invasive ventilation, intubation and mechanical ventilation and even death in, otherwise, healthy young adults (1). The CDC confirmed 57 deaths and 2,602 reported cases of EVALI throughout the United States from Aug 2019 to Jan 2020, all of whom were between the ages of 18-34 (2,3). The paucity of knowledge within the medical community with regards to the disease, its pathogenesis and targeted treatment puts clinicians at a disadvantage. We report a case of a 30-year-old male who presented to our hospital with complaints of flu-like symptoms who was initially thought to have community acquired pneumonia but was later diagnosed with EVALI in order to raise awareness, illustrate how crucial screening can affect patient outcome and the need for further investigations of this severe respiratory illness. 

Case Presentation

A 30-year-old Hispanic male with significant past medical history of intracranial hemorrhage secondary to arteriovenous malformation and craniotomy (2016) was admitted to our hospital in December 2019 after experiencing productive cough, subjective fevers, malaise, night sweats, dizziness, and fatigue for 3 days. He denied having any sick contacts or obtaining the flu vaccine, or any recent hospitalization. His admitting diagnosis was sepsis due to community acquired pneumonia and he was found to have acute renal failure which was pre-renal in nature.

Clinical findings on admission were as follows: body temperature 37°C, blood pressure 116/75mmHg, heart rate 129 beats/min, respiratory rate 18 breaths/min and oxygen saturation 99% on room air. Physical examination revealed diminished breath sounds on the right lower lobe upon auscultation. The patient’s breathing did not appear labored and he was able to speak full sentences. Laboratory tests revealed: white blood cell count of 13,000 x 10⁹/L with 88.8% neutrophils, BUN/creatinine was 29/1.59 (elevated compared to last admission in 2016), urine toxicology was positive for cannabinoids, urinalysis showed proteinuria of 100 and the rest of the biochemical testing were within normal ranges.

The initial chest x-ray (Figures 1 and 2) was read as interval development of interstitial type infiltrates in the perihilar and lower lobe distribution bilaterally, favoring pneumonia, compared to his pervious chest x-ray from 2016 which had no evidence of acute cardiopulmonary process (Figure 3).

Figures 1 and 2. Chest radiography (PA and lateral views) from the day of admission.

Figure 3. Chest radiograph from a previous admission in 2016 showing no acute cardiopulmonary process.

Sepsis bolus was given in the emergency department, blood cultures were drawn, and patient was started on ceftriaxone and azithromycin for community acquired pneumonia. Overnight, The patient spiked fever twice of 39°C at 2am and 4am the next morning. Antibiotics were broadened to vancomycin and piperacillin-tazobactam and blood cultures were repeated. Patient endorsed dyspnea and increased work of breathing requiring 2L nasal cannula. He remained tachycardic with his heart rate in the 110s despite adequate fluid resuscitation and antibiotic coverage. He also spiked an additional fever of 39.3°C at 8am. Arterial blood gas obtained showed pH 7.49, pCO₂ 33, pO₂ 70, HCO₃ 25 on 2L nasal cannula indicating acute hypoxic respiratory failure and respiratory alkalosis. Since renal function normalized, CT angiogram of the chest (Figure 4) was obtained. Although negative for pulmonary embolism, it showed extensive bilateral ground-glass lung opacities characteristic of pulmonary edema or pneumonia, noted predominantly in the lower and middle lung zones with sparing of the periphery.

Figure 4. CT angiography of the chest in lung windows, almost 24hrs after presentation to the emergency department.

Pulmonology was consulted. Upon further questioning it was discovered the patient has been vaping CBD oil and THC for about 5 years. He vapes approximately 1-2 dabbed cartridges per week which he normally obtains from a dispensary and his friends. The last time he vaped was 3 days prior to admission. He denied smoking tobacco, having a history of childhood asthma. He was started on methylprednisolone 40mg IV BID. Because his temperature became mildly elevated at 37.9°C in the afternoon, it was decided to take him for a bronchoalveolar lavage (BAL) the following day.

Respiratory viral panel, urine Legionella and urine Streptococcus pneumoniae, HIV 4^th generation screen, sputum culture and blood cultures were all negative. Procalcitonin was 3.88 ng/ml. BAL cytology revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. It was negative for fungal organisms, cytomegalovirus, Mycoplasma, tuberculosis, Pneumocystis jirovecii, Legionella, and malignant cells. Gram stain was negative as well. 

No other events occurred during the rest of his hospital course. Extensive counseling provided regarding cessation of vaping, which the patient expressed he will no longer do. His respiratory symptoms improved with the start of steroids and he was discharged on hospital day 6 with Augmentin and a 10-day prednisone taper.

Discussion

Currently, EVALI is a diagnosis of exclusion, rather than part of the initial screening for patients who present to the hospital with respiratory complaints. During our team’s initial assessment of the patient, vaping was not asked based off the reported history, imaging studies, and labs obtained by the emergency department because it appeared to be a straightforward case of sepsis secondary to community acquired pneumonia (CAP). However, despite adequate antibiotic coverage with ceftriaxone and azithromycin our patient continued to spike high fevers overnight. He did not have any risk factors for MRSA or Pseudomonas that would call for broad empiric coverage when he was first admitted based off the IDSA 2019 guidelines for treating CAP (7).

Despite sepsis fluid resuscitation, our patient remained tachycardic where his heart rate ranged between 110-120s. CT angiogram of the chest to rule out pulmonary embolism could not be done when he was admitted due to acute renal failure. A ventilation-perfusion scan would not be an appropriate study at the time due to patient’s abnormal chest x-ray. Thus, the details of the lung parenchyma could not be appreciated at the time of admission. With his continual fever spikes, we ordered the following labs to try and identify the type of infection, the possibility of a superimposed infection or resistance to the current antimicrobial regimen and if the patient was immunocompromised: flu antigens, urine Legionella and Streptococcus pneumoniae, respiratory viral panel (adenovirus, human metapneumovirus, influenza A & B, parainfluenza 1, 2 & 3, RSV, rhinovirus), HIV 4^th generation screen, sputum culture, procalcitonin and repeat blood cultures. That same morning, his antibiotics were broadened to vancomycin and piperacillin-tazobactam.

Since the patient endorsed increased work of breathing and required 2L nasal cannula when he was initially on room air when he first arrived, pulmonary embolism (PE) had to be ruled out. With his renal function back to normal, we were able to get the CT angiogram of the chest which was negative for PE but showed the largely affected parenchyma. Pulmonology was consulted because of the irregular findings and sudden decline. Based off the peripheral sparing which is characteristic for EVALI and his urine toxicology testing positive for cannabinoids, further questioning about his social history was obtained. The patient’s admission to vaping THC and CBD oil for several years and that he obtains his cartridges from dispensaries and his friends, increased the suspicion for EVALI. Based on the current literature and reports from the CDC, EVALI is largely associated with the use of THC and products obtained from informal sources such as family/friends, dealers or online sellers (1). Many times, these unregulated products contain vitamin E acetate, which is currently thought to be the culprit ingredient igniting the destruction of lung parenchyma (4). The answer remains unclear if the cause of EVALI is an inhalation injury and/or is there an intrinsic reaction sparked by the chemical reactions between the various products that causes tissue injury.

He was immediately started on methylprednisolone 40mg IV BID, based on the recommended dosing of intravenous steroids of 1mg/kg (6). However, the patient’s temperature started to rise again despite the initiation of empiric antibiotics and steroids on the same day. BAL was performed the next morning to rule out infection, malignancy or any other structural issues and only revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. The patient clinically improved with the continued regimen of vancomycin, piperacillin-tazobactam and methylprednisolone IV.

There have been notable case reports with regards to EVALI that illustrate its various presentations and some of the barriers that make it difficult to diagnose. Salzman et al. (8) presented a case of a 27-year-old Caucasian female who developed acute eosinophilic pneumonia associated with electronic cigarettes. CBC at the time of admission showed WBC of 24,400 with 47% eosinophils. Although she admitted to vaping both nicotine and THC products for at least three years, three months prior to admission, she was vaping exclusively JUUL pods with nicotine blueberry and mint flavors. Her symptoms were severe enough that she required a one day stay in the ICU. She was treated with oral prednisone 50mg daily for a total of 5 days and oral doxycycline 100mg BID with improvement in her symptoms. This brings up the question whether her prior vaping history already jeopardized her lung parenchyma thus putting her at higher risk for developing EVALI.

In Schmitz’ (9) case report of a 38-year-old obese female with fibromyalgia on chronic prednisone (20mg daily), she admits to having started vaping CBD oil one month prior to admission. On BAL she was found to have diffuse upper and lower airway erythema with significant coughing, elevated eosinophil count (59%) and foamy macrophages which is associated with EVALI. She was started on methylprednisolone 1000mg daily, without antibiotics and experienced rapid improvement within a couple of days.

Works and Stack (5) discussed the case of a 20-year-old male who had several hospital admissions due to complaints of productive cough, high grade fever, gastrointestinal symptoms of diarrhea/nausea and 20lb unintentional weight loss over 3 weeks. The patient initially was treated at another hospital with ceftriaxone, levofloxacin and azithromycin and did not complete the course of antibiotics because they left against medical advice since they did not experience any improvement. On admission, the patient was found to have a very high leukocytosis with WBC of 44,800 and was not started immediately on empiric antibiotics. Instead, he was started on prednisone 1mg/kg and Bactrim after the BAL failed to yield an infectious cause. The patient was also noted to have obtain his THC cartridges from an outside source, like our patient.

Panse’s (10) case of a 25-year-old male who previously smoked 1-2packs per day and quit 6 months prior to admission was not forthcoming about vaping. Both CT scans showed multifocal ground-glass opacities with features of small airway obstruction. He underwent bronchoscopy and transbronchial biopsy which did not provide enough information to make a diagnosis. A video-assisted thorascopic lung biopsy was performed and showed acute and organized lung injury with interstitial edema, type II pneumocyte hyperplasia, alveolar fibrin deposition, acute fibrinous pneumonitis, lipid-laden macrophages and foci of organizing pneumonia consistent with EVALI. This is a prime example of how omission of vaping history delays diagnosis, leads to invasive procedures and although it did not happen in this particular situation, can result in death (10). Unlike the patient in Panse’s case, our patient easily admitted to vaping. Non-disclosure of medically relevant information such as vaping, is a problem clinicians will run into especially since it is a key piece of information needed to diagnose EVALI. Many patients withhold information from their doctors, especially those that they may find embarrassing, feel that they will be judge or lectured, or not wanting to hear about associated harm. Quantifying how many patients are withholding information or how many cases are not being accounted for because the person does not want to admit they are vaping would be difficult.

Formal diagnostic criteria for EVALI has not been agreed upon which can be attributed to the various forms of lung injury. We were able to diagnose our patient based of the suggested criteria of e-cigarette or vaping in the previous 90 days, lung opacities on chest x-ray or CT, exclusion of infection, and the absence of alternative diagnosis (cardiac, neoplastic or rheumatologic) (1). In a case series by Kalininskiy et al. (12), the University of Rochester Medical Center (Rochester, New York, USA) created a clinical practice algorithm to allow for the rapid identification of suspected EVALI based on history, clinical presentation and chest imaging, which is similar to the CDC however it focuses on vaping activity from the past 30 days rather than 90 days.

Currently, the treatment of EVALI is empiric antibiotics for community acquired pneumonia, systemic glucocorticoids in those with worsening symptoms, and supportive therapy with supplemental oxygen (6). In our case, the patient improved with the combination of vancomycin, piperacillin-tazobactam and methylprednisolone. The efficacy of systemic glucocorticoids is still unknown (1). However, it still remains unclear whether it was the combination of those specific antibiotics in conjunction with steroids, the combination of vancomycin and piperacillin-tazobactam only or solely systemic glucocorticoids. Since CAP is more common, it should not be overlooked and go untreated. Further investigation needs to be done for more targeted therapy.

The long-term effects of EVALI in those who were treated are still not well known. It is currently recommended for repeat imaging to determine if the treatment regimen was successful. However, many patients are lost to follow-up, as was the case for our patient due to lack of insurance.

Our case report illustrates how crucial early identification of EVALI affects patient care. It is imperative clinicians screen for the disease to prevent further complications. We recommend the following screening criteria: although the population greatly affected by the EVALI epidemic have been predominantly males between the ages of 18-34 (37% of the cases reported to the CDC as of Jan 14, 2020 are age 18-24, and 24% are 25-34, with a 66% male predominance) it should include all those who vape or use e-cigarettes regardless of age or gender as illustrated with the aforementioned case reports (13). Patients who presents with respiratory symptoms, especially if they are similar to pneumonia, such as dyspnea, increased work of breathing, fevers/chills, productive cough, chest pain, pleurisy, hemoptysis, and noted hypoxemia should be asked more than just smoking history with regards to cigarettes. They should be asked about prior E-cigarettes usage or vaping in the past, when was the last use, what kind of products were used and were they concentrated/dabbed and where it was obtained. Clinical suspicion should be increased if patients admit to THC or CBD use, but nicotine, flavorings and additives should not be disregarded. Urine drug screen should be ordered if there is a strong clinical suspicion, and the patient is denying prior THC use. EVALI has also been associated with gastrointestinal symptoms of abdominal pain, diarrhea, and nausea/vomiting. It is important to rule out infectious causes, by asking about sick contacts, recent hospitalizations, history of HIV and use of immunologic agents that can cause one to be immunocompromised. Patients should be screened about airway diseases such as asthma, COPD, and interstitial lung disease since they could have already caused chronic changes to lung parenchyma. There is still so much that the medical community does not know about EVALI. Further investigations still need to be pursued to improve the medical community’s diagnosis and treatment of this serious respiratory epidemic.

Disclaimer

This research was supported (in whole or in part) by HCA and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA or any of its affiliated entities.

References

1. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin - final report. N Engl J Med. 2020 Mar 5;382(10):903-16. [CrossRef] [PubMed]
2. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. January 17, 2020.Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#key-facts (accessed 3/10/20).
3. Ellington S, Salvatore PP, Ko J, et al. Update: product, substance-use, and demographic characteristics of hospitalized patients in a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury - United States, August 2019-January 2020. MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):44-9. [CrossRef] [PubMed]
4. Blount BC, Karwowski MP, Shields PG, et al. Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI. N Engl J Med. 2020 Feb 20;382(8):697-705. [CrossRef] [PubMed]
5. Works K, Stack L. E‐cigarette or vaping product‐use‐associated lung injury (EVALI): A case report of a pneumonia mimic with severe leukocytosis and weight loss. JACEP Open. 2020;1-3. [CrossRef]
6. Triantafyllou GA, Tiberio PJ, Zou RH, et al. Vaping-associated acute lung injury: a case series. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1430-1. [CrossRef] [PubMed]
7. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. [CrossRef] [PubMed]
8. Salzman GA, Alqawasma M, Asad H. Vaping associated lung injury [EVALI]: an explosive United States epidemic. Mo Med. 2019 Nov-Dec;116(6):492-6. [PubMed]
9. Schmitz ED. Severe respiratory disease associated with vaping: a case report. Southwest J Pulm Crit Care. 2019;19[3]:105-9.[CrossRef]
10. Panse PM, Feller FF, Butt YM, Gotway MB. February 2020 imaging case of the month: an emerging cause for infiltrative lung abnormalities. Southwest J Pulm Crit Care. 2020;20(2):43-58. [CrossRef]
11. Levy AG, Scherer AM, Zikmund-Fisher BJ, Larkin K, Barnes GD, Fagerlin A. Prevalence of and factors associated with patient nondisclosure of medically relevant information to clinicians. JAMA Netw Open. 2018 Nov 2;1(7):e185293. [CrossRef] [PubMed]
12. Kalininskiy A, Bach CT, Nacca NE, Ginsberg G, Marraffa J, Navarette KA, McGraw MD, Croft DP. E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. Lancet Respir Med. 2019 Dec;7(12):1017-26. [CrossRef] [PubMed]
13. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. February 5, 2020. Available at:  https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#map-cases (accessed 3/10/20).

Cite as: Josef V, Tu G. Case report: the importance of screening for EVALI. Southwest J Pulm Crit Care. 2020;20(3)87-94. doi: https://doi.org/10.13175/swjpcc012-20 PDF 

Severe Respiratory Disease Associated with Vaping: A Case Report

Evan Denis Schmitz MD

La Jolla, CA USA

Abstract

A case of severe respiratory disease associated with vaping cannabinoid oil is reported in a 38-year-old woman. She presented with shortness of breath and nonproductive cough. Chest x-ray and CT scan showed diffuse ground glass opacities and consolidation. Bronchoscopy showed diffuse bronchial erythema and bronchoalveolar lavage contained an increased percentage of eosinophils (59%). She was treated with high dose corticosteroids and rapidly improved.

Case Report

History of Present Illness

A 38-year-old woman complained of worsening shortness of breath and nonproductive cough for four weeks. She used to be able to climb three flights of stairs but now can barely walk ten feet. She had been treated with various forms of antibiotics, inhalers and steroids and was taking 20 mg of prednisone a day on the day of hospitalization. She also received opiates to help control her cough. She denied any hemoptysis, fever, chills, or sputum production. Because of her progressive symptoms she was hospitalized for further evaluation and management.

Past Medical History, Social History and Family History

She has a history of obesity and fibromyalgia. She has a prior history of smoking one to two packs a day for five years quitting approximately 15 years ago. Because of a family crisis she tried vaping cannabidiol (CBD) oil approximately one month prior to admission. She also resumed smoking tobacco one half a pack per day. Her family history was unremarkable.

Medications

She was taking prednisone 20 mg/day and cyclobenzaprine (Flexeril®) for her fibromyalgia. She was also taking codeine cough syrup.

Review of Symptoms

She did have some chest pain associated with her shortness of breath as well as chronic muscle aches and intermittent lower extremity edema. Her review of systems was otherwise unremarkable.

Physical Examination

Vital Signs: BP 137/72 mm Hg, Pulse 84 beats/min, temperature 98.8 °F, respirations 22 breaths/min, height 5’0, weight 231 lbs, SpO2 96%

General: She was morbidly obese and only able to speak in short sentences.

Mouth: Moist. Mallampati 3.

Pulmonary: Faint expiratory crackles. No wheezing.

Cardiovascular: Normal rate, regular rhythm, normal heart sounds and intact distal pulses. Exam reveals no gallop and no friction rub. No murmur heard.

Abdominal: Soft, bowel sounds normal. No distension, mass or tenderness. No rebound or guarding. Centripetal obesity.

Extremities: Normal range of motion. No edema or tenderness.

Lymphatics: No cervical or supraclavicular adenopathy.

Neurological: Alert and oriented to person, place and time.

Skin: Warm and dry. No rash, erythema or pallor. Not diaphoretic. Capillary refill within normal limits. No skin tenting.

Psychiatric: Depressed mood.

Laboratory

Pertinent findings are on her laboratory evaluation include an elevated white blood cell count of 16,850 cells/µL with an increased number of neutrophils. Her electrolytes, liver enzymes, creatinine, blood urea nitrogen and urinalysis were within normal limits.

Radiology

Her admission chest x-ray is shown in Figure 1.

Figure 1. The admission portable chest x-ray showed bilateral patchy pulmonary infiltrates.

To better define the areas of consolidation, a thoracic CT scan was performed (Figure 2).

Figure 2. Representative images in lung windows from contrast enhanced thoracic CT scan showing nonspecific patchy areas of ground glass and alveolar opacities with septal thickening involving both lungs.

Hospital Course

Echocardiography was unremarkable. Bronchoscopy with bronchoalveolar lavage was performed. She had diffuse upper and lower airway erythema and considerable coughing during the procedure. The cell differential revealed an increase in eosinophils (59%) and multiple foamy macrophages. Smears and cultures of the lavage fluid were negative for pathogens. She was treated with high dose corticosteroids (methylprednisolone 1000 mg/day). She rapidly improved over four days with her cough and shortness of breath resolving. A chest x-ray at discharge revealed improvement of the pulmonary infiltrates (Figure 3).

Figure 3. Chest x-ray on the morning of discharge showing near resolution of her pulmonary infiltrates.

Discussion

At the time of this writing (9/21/19) there have been 530 cases of lung injury associated with e-cigarette product use or vaping reported with seven deaths (1).  Nearly three fourths (72%) of cases have been male with two thirds (67%) 18 to 34 years old. Most patients have reported a history of using e-cigarette products containing tetrahydrocannabinol (THC). Many patients have reported using THC and nicotine. Some have reported the use of e-cigarette products containing only nicotine.

At present no specific e-cigarette or vaping product (devices, liquids, refill pods, and/or cartridges) or substance has been linked to all cases. It seems likely that there may be different mechanisms of lung injury from different substances. In support of this concept, the present case had high numbers of eosinophils in the bronchoalveolar lavage while other cases have shown an increase in neutrophils (2). Our patient was treated with high dose corticosteroids and did improve while on the corticosteroids. However, the time course does not establish a definite relationship between corticosteroid treatment and her improvement.

At present the CDC recommends refraining from using e-cigarette or vaping products (1). Anyone who uses an e-cigarette or vaping product should not buy these products (e.g., e-cigarette or vaping products with THC or CBD oils) off the street, and should not modify or add any substances to these products that are not intended by the manufacturer.

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. September 19, 2019. Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html (accessed 9/21/19).
2. Arizona Thoracic Society. September 2019 Arizona thoracic society notes. Southwest J Pulm Crit Care. 2019;19(3):99-100. [CrossRef]

Cite as: Schmitz ED. Severe respiratory disease associated with vaping: a case report. Southwest J Pulm Crit Care. 2019;19(3):105-9. doi: https://doi.org/10.13175/swjpcc062-19 PDF