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] 
2. 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] 
3. Taylor J, Wiens T, Peterson J, et al. Characteristics of E-cigarette, or Vaping, Products Used by Patients with 18 and 2019. MMWR Morb Mortal Wkly Rep. 2019 Nov 29;68(47):1096-1100. [CrossRef] [PubMed]
4. Rachid M, Yin J, Mier N, et al. Reversed Takutsubo Cardiomyopathy in a young patient with vaping induced acute lung injury. ATS International Conference Abstract Presentation. 2020 May 15-20. Philadelphia, PA. Abstract nr A1839.
5. Aberegg SK, Maddock SD, Blagev DP, Callahan SJ. Diagnosis of EVALI: General Approach and the Role of Bronchoscopy. Chest. 2020 Aug;158(2):820-827. [CrossRef] [PubMed]
6. Blagev DP, Harris D, Dunn AC, Guidry DW, Grissom CK, Lanspa MJ. Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study. Lancet. 2019 Dec 7;394(10214):2073-2083. [CrossRef] [PubMed]
7. Kalininskiy A, Bach CT, Nacca NE, et al. E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. Lancet Respir Med. 2019 Dec;7(12):1017-1026. [CrossRef] [PubMed]
8. Heinzerling A, Armatas C, Karmarkar E, et al. Severe Lung Injury Associated With Use of e-Cigarette, or Vaping, Products-California, 2019. JAMA Intern Med. 2020 Jun 1;180(6):861-869. [CrossRef] [PubMed]
9. Puebla Neira D, Tambra S, Bhasin V, Nawgiri R, Duarte AG. Discordant bilateral bronchoalveolar lavage findings in a patient with acute eosinophilic pneumonia associated with counterfeit tetrahydrocannabinol oil vaping. Respir Med Case Rep. 2020 Feb 3;29:101015. [CrossRef] [PubMed]
10. Henry TS, Kanne JP, Kligerman SJ. Imaging of Vaping-Associated Lung Disease. N Engl J Med. 2019 Oct 10;381(15):1486-1487. [CrossRef] [PubMed]
11. Thakrar PD, Boyd KP, Swanson CP, Wideburg E, Kumbhar SS. E-cigarette, or vaping, product use-associated lung injury in adolescents: a review of imaging features. Pediatr Radiol. 2020 Mar;50(3):338-344. [CrossRef] [PubMed]
12. Larsen BT, Butt YM, Smith ML. More on the Pathology of Vaping-Associated Lung Injury. Reply. N Engl J Med. 2020 Jan 23;382(4):388-390. [CrossRef] [PubMed]
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 

December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites?

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 88-year-old man who has been short of breath and febrile up to 101.5° F for the past day presented on October 20, 2020. He has no known sick contacts or exposure to COVID-19.

PMH, SH, and FH

• No reported pulmonary history although he had a Xopenex MDI which he rarely used.
• Coronary artery disease with prior coronary artery bypass grafting (1978); multiple subsequent stents; chronic atrial fibrillation; pacemaker (Micra)
• Stage 3-4 CKD (creatinine 1.95)
• Chronically on warfarin

Physical Examination

• Temp 37.3, Sat 92% on RA, 95% on 2 lpm,
• Lungs: Few crackles in right upper chest
• CV: regular, no murmur
• Ext: 1 to 2+ edema (chronic, uses TED hose)

Which of the following is/are the most likely diagnosis? (Click on the correct answer to be directed to the second of seven pages)

1. Community-acquired pneumonia
2. Congestive heart failure
3. COVID-19
4. 1 and 3
5. Any of the above

Cite as: Wesselius LJ. December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites? Southwest J Pulm Crit Care. 2020;21(6):128-37. doi: https://doi.org/10.13175/swjpcc065-20 PDF

January 2017 Pulmonary Case of the Month

Jamie Bering, MD

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

The patient is a 53-year-old woman transferred for acute respiratory failure and hemoptysis. She has a prior history of antiphospholipid syndrome and recurrent diffuse alveolar hemorrhage (DAH). She was admitted to another hospital about 2 weeks prior to transfer with hypoxic respiratory failure which ultimately required intubation. Bronchoscopy revealed a bloody aspirate raising concerns for recurrent DAH. She was started on high-dose solumedrol and extubated after 4 days. One week later, her respiratory status decompensated and her chest x-ray showed worsening diffuse bilateral opacities concerning for recurrent DAH. She was transferred to the Mayo Clinic Arizona for further evaluation. Upon arrival, she required 50% FiO2 by face mask to maintain adequate oxygenation and was started on broad-spectrum antibiotics. Her corticosteroids were tapered to 20 mg prednisone daily.

Past Medical History, Social History and Family History

She has a history of a mitral valve replacement with a St. Jude’s mechanical mitral valve and was on chronic anticoagulation with warfarin. In addition, there was a history of moderate aortic stenosis with moderate aortic insufficiency.

She had a history of diffuse alveolar hemorrhage, antiphospholipid antibody syndrome and possible systemic lupus erythematosus.

Medications

• Dapsone 100mg daily
• Ethacrynic acid 75mg daily
• Gabapentin 900mg QHS
• Lisinopril 20mg daily
• Meropenem 1g Q8 hrs
• Metoprolol 50 mg BID
• Prednisone 20mg daily
• Simvastatin 40mg QHS
• Vancomycin 1.5g Q12 hrs
• Warfarin 4mg T,F; 3mg SMWRSa

Physical Examination

• Vitals: T 36.3^◦ C; HR 79 beats/min; BP 100/63 mm Hg; RR 26 breaths/min; SpO2 99% face mask
• Gen: no acute distress
• HEENT: hematoma on chin
• Lungs: clear to auscultation and percussion
• Cardiac: Mechanical valve click

Laboratory

• CBC: WBC 15,900 cells per microliter (mcL); Hemoglobin 9.1 g/dL; hematocrit 29%; platelet count 156,000 cells per microliter.
• Electrolytes: within normal limits.
• BUN and creatinine: within normal limits.
• Blood sugar: 220 mg/dL.

Radiography

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

Figure 1. Initial chest radiograph.

Which of the following best describes the chest x-ray? (Click on the correct answer to proceed to the second of four pages)

1. Diffuse lung consolidation
2. Previous median sternotomy
3. Previous mitral valve replacement
4. 1 and 3
5. All of the above

Cite as: Bering J, Wesselius LJ. January 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2016;14(1):1-5. doi: https://doi.org/10.13175/swjpcc146-16 PDF

Pulmonary Hantavirus Syndrome: Case Report and Brief Review

Charles J. VanHook, MD

Britt Warner, PA

Angela Taylor, MD

Longmont United Hospital

Longmont, Colorado

A 31-year-old white man presented to the emergency department complaining of fever, headache, mild confusion, and muscle aches. Approximately three days earlier he had developed non-quantified fever and diffuse muscle aches and pains. He was employed as a feedlot worker. He had visited an urgent care center one day earlier and had been advised to increase his oral fluid intake and to use non-steroidal anti-inflammatory agents as needed. Upon arrival to the emergency department he was found to have a temperature of 103.6º Fahrenheit, blood pressure of 125/72 mm Hg, respiratory rate of 40 breaths per minute, and room-air oxygen saturation of 84% by pulse oximetry. Auscultation of the chest disclosed diffuse rales. Heart sounds were rapid and regular. Abdominal exam was benign. There was no skin rash. Central nervous exam demonstrated agitation and confusion, but was otherwise non-focal. Laboratory examination revealed a white blood count of 11.7 K/uL, hemoglobin of 21.5 g/DL, hematocrit of 66.8%, platelet count of 73 K/uL, partial thromboplastin time of 36 seconds, lactic acid of 2.4 mm/L, and procalcitonin of 43 ng/mL. Chest radiograph disclosed extensive bilateral infiltrates (Figure 1).

Figure 1. Chest x-ray showing bilateral infiltrates

The patient precipitously declined, with severe respiratory distress, and was emergently intubated. Despite aggressive measures, including mechanical ventilation with an FIO2 of 1.0 and PEEP of 18 cm H2O, vigorous intravenous intravenous fluid resuscitation with normal saline, and pressor support with intravenous norepinephrine and vasopressin, the patient developed refractory hypoxemia. This was followed by a bradycardic arrest and death 2 hours after presentation. Serology sent at the time of admission later returned as IgM positive for hantavirus, with subsequent testing positive for Sin Nombre IgM.

Hantaviruses are RNA viruses of the family Bunyaviridae that are transmitted to humans by contact with the saliva, urine, or feces of infected rodents, which serve as persistently infected hosts (1). Patients who work in proximity to rodents, such as animal trappers, farmers, and forestry workers are at highest risk for infection. In the Western Hemisphere, there are approximately 200 cases per year of Hantavirus Pulmonary Syndrome (HPS), which was first identified in the Four Corners area of the Southwestern United States in 1993 (2). In the United States, HPS is most commonly caused by the Sin Nombre subfamily of hantavirus. A two-week incubation period precedes a 3-6 day prodromal period during which fever and myalgia are prominent features. The cardiopulmonary phase of HPS follows, with the development of acute non-cardiogenic pulmonary edema and multi-organ dysfunction. Typical laboratory abnormalities are leukocytosis and thrombocytopenia. Elevations in hematocrit and partial thromboplastin time are strong predictors of mortality, which approaches 40%. Definitive diagnosis depends on the serologic identification of IgM antibody to hantavirus using ELISA technology.  Immunochromatographic technology may allow for same day diagnosis (3). Treatment is supportive, and varies with the severity of disease. It may include volume resuscitation, ventilatory support, and renal replacement therapy. There is no established anti-viral therapy for Hantavirus infection, although ribavirin is often used in Asia. Corticosteroids have also been used sporadically with some success, but their use remains controversial (3).

Although Hantavirus remains a rare disease, prodromal symptoms in a patient with associated epidemiologic risk factors should heighten clinical suspicion.

References

1. Lednicky JA. Hantavirus: A short review. Arch Pathol Lab Med. 2003;127:30-35. [PubMed]
2. Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki S, Ksiazek TG, Rollin PE, Nichol S, Umland E, Moolenaar RL, Reef SE, Nolte KB, Gallaher MM, Butler JC, Breiman RF. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. N England J Med 1994;330:949-55 [CrossRef] [PubMed]
3. Bi Z, Formenty P, Roth C Hantavirus infection: A review and global update. J Infect Developing Countries. 2008;2(1):3-23. [CrossRef] [PubMed]

Cite as: VanHook CJ, Warner B, Taylor A. Pulmonary hantavirus syndrome: case report and brief review. Southwest J Pulm Crit Care. 2015;11(3):121-3. doi: http://dx.doi.org/10.13175/swjpcc122-15 PDF

Bronchoscopic Cryoextraction: A Novel Approach for the Removal of Massive Endobronchial Blood Clots Causing Acute Airway Obstruction

Bhaskar Bhardwaj MBBS (bhaskar_bhardwaj@hotmail.com)¹

Himanshu Bhardwaj MD (himanshu-bhardwaj@ouhsc.edu)²

Houssein A. Youness MD (houssain-youniss@ouhsc.edu)²

Ahmed Awab MD (ahmad-awab@ouhsc.edu)²

¹Indira Gandhi Medical College, Department of Pulmonary Medicine and Tuberculosis,  Shimla, Himachal Pradesh, India

²Pulmonary Medicine & Critical Care, University of Oklahoma Health Sciences Center, Oklahoma City. USA

Abstract

Acute airway obstruction due to large blood clots is known to cause life threatening hypoxemic respiratory failure which can be challenging to diagnose and manage. Different bronchoscopic modalities like rigid bronchoscopy, forceps, snares and catheters can be used to extract these obstructing blood clots but each of these different methods have their own limitations.  We describe a patient with iatrogenic endobronchial bleed with acute airway obstruction due to massive blood clot successfully managed using ‘cryoextraction’. This technique has been described as the treatment of choice for this clinical situation and this case highlights the fact that this technique can save patients from more aggressive invasive procedures. 

Introduction

Bronchoscopic cryoextraction using a cryoprobe is an infrequently used   therapeutic modality for the removal of tracheobronchial tree foreign bodies, especially those containing sufficient water or freezable liquid (1). This technique uses a liquid cryogen or coolant (usually nitrous oxide, nitrogen, or carbon dioxide) which is delivered under pressure to a specially designed cryoprobe that can be passed through the working channel of the flexible bronchoscope (2).  We present a case of acute life-threatening airway obstruction caused by large iatrogenic blood clots which was successfully managed using cryoextraction.

Case Report

A 54 years old male with history of renal transplant and chronic immune suppressive therapy was admitted to the intensive care unit with productive cough, fevers and dyspnea of 3 days duration. His initial vital signs showed blood pressure at 140/100 mm Hg, pulse 110, respiratory rate at 36, temperature 102 degree Fahrenheit and initial oxygen saturation of 70 % on supplemental nasal cannula oxygen at 4 liters/min.   Physical examination revealed diffuse bronchial breath sounds in the right lower lung fields and chest radiograph showed consolidation in the right lower lobe. (Figure 1).

Figure 1. Pre BAL chest radiograph showing right lower lobe consolidation consistent with pneumonia.

Arterial blood gas analysis was consistent with partial pressure of oxygen (PaO2) at 40 mm Hg. Patient remained hypoxic despite supplemental oxygen and eventually required endotracheal intubation with mechanical ventilation due to hypoxic respiratory failure. Patient was also started on empiric antibiotic therapy with ceftriaxone and azithromycin for severe community acquired pneumonia requiring intensive care unit care. Unfortunately, patient’s clinical condition deteriorated in next 48 hours despite continuous antibiotics. His oxygen requirements kept on escalating on mechanical ventilation besides continuous ongoing fever.

At this point, we decided to perform a bronchoscopy with a plan for bronchoalveolar lavage (BAL) given the high risk for atypical lung infections secondary to chronic immunosuppression in this patient. Airway examination during BAL showed extremely friable endobronchial mucosa with thick purulent secretions in the right lower lobe bronchi. Unfortunately, a massive endobronchial bleeding caused by an iatrogenic bronchial mucosal tear complicated the procedure. The most likely cause for this bleeding complication was bronchoscope induced mucosal trauma accentuated by vulnerability of the mucosal capillaries due to ongoing immunosuppression and pneumonia in this patient. BAL was terminated but patient became extremely hypoxic despite increasing fraction of inspired oxygen from initial 50% to 100%. Acute rise in peak airway pressures to 56 cm H2O were also noted. An urgent repeat chest radiograph showed worsening of right lower lobe consolidation with new atelectasis suggestive of an acute airway obstruction (Figure 2).

Figure 2.  Post BAL chest radiograph showing acutely worse right lower lobe infiltrates, consistent with atelectasis and acute airway obstruction due to massive blood clot.

Repeat flexible bronchoscopic exam showed a massive blood clot extending from right main stem bronchus to lower bronchi obstructing the bronchial lumen almost completely. Removal of blood clot was felt to be necessary to improve the hypoxia. Initial attempts to suction the endobronchial clots through flexible bronchoscope and forceps extraction were unsuccessful due to extremely friable nature of the fresh blood clot. We decided to use cryoextraction to remove the endobronchial clot emergently.

A flexible cryoprobe (ERBE cryotherapy system – 1.9 mm size cryoprobe) was extended through the working channel of the bronchoscope into the bronchi, was applied to the clot & frozen for 10 seconds. Frozen clot got firmly attached to the probe and it was successfully pulled out in one large piece (Figure 3).

Figure 3. Massive blood clot extracted from airways, attached to the cryoprobe.

This resulted in immediate improvement in patient’s oxygenation. Patient remained on mechanical ventilation and a repeat bronchoscopic airway examination next day did not show any further bleeding. A non-bleeding mucosal tear in the right main bronchus was identified as the possible source of initial bleed. Patient eventually improved with continued treatment; he was successfully extubated after one week of mechanical ventilatory support.  He was discharged home after total 2 weeks of hospitalization.   

Discussion

Acute airway obstruction due to endobronchial blood clots is an unusual, but not a rare event which can develop in variety of clinical settings like various pulmonary infections, bronchial carcinoma, intrathoracic trauma etc. Some of the common interventions reported to cause acute airway bleeding and subsequent bronchial obstruction due to blood clots include: Iatrogenic mucosal damage from suction catheter manipulation, bronchoalveolar lavage, transbronchial biopsy and tracheostomy placement (Table1) (3).

Clinical consequences of the acute bronchial obstruction can range from minimal impact on respiratory function to life threatening ventilator failure. Pertinent physical examination findings in these patients include decreased or absent breath sounds with occasional inspiratory or expiratory wheezing heard over the affected lobe or lung. Among mechanically ventilated patients, acute rise in peak inspiratory pressure (above 60 cm H2O) with decreased tidal volume are some other notable findings. One unusual presentation of massive endobronchial bleeding in mechanically ventilated patients occurs when the clot adheres to the distal end of the endobronchial tube resulting in ball-valve type obstruction. In this situation, the clot acts as one-way valve allowing only the inspiratory flow into the lower respiratory tract but blocking the expiratory flow. This mechanism can result in unilateral or bilateral lung hyperexpansion, thus increasing the risk of tension pneumothorax. Urgent endobronchial tube exchange in this situation can be lifesaving (3). The extent of hypoxemia due to endobronchial blood clot obstruction depends on the site, degree of obstruction and underlying condition of the lungs (3). Typical imaging findings include lobar or segmental atelectasis or air column cut-off of the trachea and main stem bronchi. The diagnosis is confirmed by direct visualization of the clot through flexible bronchoscope. Initial efforts targeted at the removal of the blood clot involve suctioning and grasping forceps extraction of the clot through a flexible bronchoscope. However, these methods often prove unsuccessful due to the friable structure of the blood clots. Moreover, suctioning through the flexible bronchoscope could pose a risk of re-bleeding. Other management options include rigid bronchoscopy, Fogarty catheter dislodgment of the clot and sometimes the use of topical thrombolytic agents with partial dissolution of clot aiding in suction removal of the clot in piecemeal fashion. Rigid bronchoscopy with clot extraction was used to be the treatment to choice for the management of acute obstructing endobronchial blood clots but it requires general anesthesia and may not be as readily available as needed for these acutely sick patients (4,5).

Cryoextraction using flexible cryoprobe is an underreported novel approach which can be successfully used in removal of large blood clots from the airways. One of the first descriptions of the use of cryoextraction in the removal of endobronchial blood clots was given by Mehta et al in one of their review about various interventions used in tracheobronchial foreign body extraction (6). This method allows freezing of the water component of the blood clots, leading to their removal in en-bloc. Additionally, freezing also has a hemostatic effect through vasoconstriction and rapid slowing of the circulation. Cryoextraction can also be used to extract mucus plugs and other foreign bodies containing some amount of freezable liquid. Under circumstances in which a foreign body does not have any or enough water content, one may consider spraying saline over the object and immediately freezing the foreign body; thus allowing successful cryoextraction. Freezing also leads to shrinking of the foreign objects, thereby easily separating them from inflamed mucosa and facilitating their removal. An additional advantage of this technique is the shorter learning curve needed to utilize the cryoprobe compared to the prolonged training required to master rigid bronchoscopy (7). One concern expressed about the cryoextraction of the massive endobronchial clots is that a large ‘frozen clot’ might be difficult to extract through the smaller sized endotracheal tubes and, if dislodged in that process, could lead to obstruction of the ET tube. 

Conclusion

Our case report illustrates the successful use of cryoextraction as a safe and cost effective tool which can be used in the quick removal of large airway clots causing symptomatic airway obstruction. This modality should be considered as the first line treatment in this clinical situation.¹ Cryoextraction method can also spare patients from more invasive procedures like rigid bronchoscopy often used in these scenarios.⁶ In the absence of well-designed studies, this method must be objectively compared with other methods and more cases are needed to be analyzed in future studies.    

References

1. Weerdt S, Noppen M, Remels L, et al. Successful removal of a massive endobronchial clot by means of cryotherapy. J Bronchol. 2005; 12:23-24. [CrossRef]
2. Rafanan AL, Mehta AC. Adult airway foreign body removal. What's new? Clin Chest Med 2001; 22:319. [CrossRef]
3. Arney KL, Judson MA, Sahn SA. Airway obstruction arising from blood clot: three reports and a review of the literature. Chest. 1999; 115(1):293-300. [CrossRef] [PubMed]
4. Schummer W, Schummer C. Hemorrhagic Tracheobronchial obstruction. J Bronchol. 2001; 8(3):236. [CrossRef]
5. Homasson JP, Vergnon JM .Cryotherapy to extract obstructing blood clots. J Bronchol 2002;9:158-9. [CrossRef]
6. Mehta AC, Rafanan A. Extraction of airway foreign body in adults. J Bronchol. 2001; 8:123–131. [CrossRef]
7. Rubio E, Gupta P, Ie S, Boyd M. Cryoextraction: a novel approach to remove aspirated chewing gum. Ann Thoracic Med. 2013; 8(1):58-59. [CrossRef] [PubMed]

Conflict of Interest disclosures: No financial or nonfinancial conflicts of interests exist for any of the involved authors.

Reference as: Bhardwaj B, Bhardwaj H, Youness HA, Awab A. Bronchoscopic cryoextraction: a novel approach for the removal of massive endobronchial blood clots causing acute airway obstruction. Southwest J Pulm Crit Care. 2013;7(3):184-9. doi: http://dx.doi.org/10.13175/swjpcc112-13 PDF 

July 2013 Pulmonary Case of the Month: Swan Song

Bridgett Ronan, MD

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 53 year old man presented to the emergency department with a 2 week history of progressive dyspnea. He thought it was anxiety due to quitting drinking just before the onset of his symptoms. He also had fatigue and malaise.

PMH, SH, FH

He had no significant past medical history or family history. He did not smoke but drank 2-6 beers/day until 2 weeks prior to presentation.

Physical Examination

BP 110/60 mm Hg, P 110 beats/min, R 32 breaths/min, T 37.6° C, SpO2 81%

He is pale and appears mildly dyspneic otherwise his physical exam is unremarkable.

Chest Radiography

His chest x-ray is shown in figure 1.

Figure 1. Initial PA (Panel A) and lateral (Panel B) chest x-ray. 

Which of the following laboratory tests is/are not indicated?

1. Arterial blood gases
2. Complete blood count
3. Spiral thoracic CT angiography
4. Urinanalysis
5. All of the above

Reference as: Ronan B, Wesselius LJ. July 2013 pulmonary case of the month: swan song. Southwest J Pulm Crit Care. 2013;7(1):1-9.  doi: http://dx.doi.org/10.13175/swjpcc081-13. PDF