December 2024 Pulmonary Case of the Month: Two Birds in the Bush Is Better than One in the Hand

Susanna G. Von Essen MD

University of Nebraska Medical Center

Omaha, NE USA

History of Present Illness

A 48-year-old man is referred for dyspnea on exertion and a nonproductive cough. He was well until 6 months prior to this visit. He feels he has had “flu-like symptoms” over the past month.

PMH, SH, and FH

He has had intermittent atrial fibrillation controlled by digoxin but also clopidogrel as an anticoagulant. He has symptoms of hay fever and had asthma as a child.

He has never smoked and rarely drinks. Pets include two dogs and a cat. He is a university English literature professor and his office is an old building but the building is clean and well maintained.  Hobbies include playing guitar in a rock-n-roll band.

His family history is unremarkable.

Physical Examination

His physical examination including  lungs and cardiovascular examination is unremarkable.

Which of the following are indicated for further workup? (Click on the correct answer to be directed to the second of six pages.)

1. Chest X-ray
2. Electrocardiogram (ECG)
3. Pulmonary function testing (PFTs)
4. 1 and 3
5. All of the above

Cite as: VonEssen SG. December 2024 Pulmonary Case of the Month: Two Birds in the Bush Is Better than One in the Hand. Southwest J Pulm Crit Care Sleep. 2024;29(6):53-56. doi: https://doi.org/10.13175/swjpccs035-24 PDF.

June 2024 Pulmonary Case of the Month: A Pneumo-Colic Association

Lewis J. Wesselius MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

The patient is a 57-year-old woman who presented to the emergency department with increasing cough and shortness of breath over several days. She has a history of ulcerative colitis complicated by toxic megacolon with subsequent colectomy.

Past Medical History, Family History and Social History

• Ulcerative colitis with history of toxic megacolon (4 years prior), s/p total colectomy

• History of recent respiratory failure thought secondary to ustekinumab (Stelara).  The respiratory failure responded well to steroid therapy.

• She has a history of latent Tb treated with rifampin

• Anxiety

Medications

• Clonazepam 1.0 mg daily at bedtime

• Gabapentin 300 mg TID

• Pantoprazole 40 mg BID

• Prednisone 5 mg daily

Physical Examination

• Mild-moderate respiratory distress

• Afebrile. SpO2 87% on room air. Oxygen saturation 94% on 2 lpm supplemental oxygen.

• Chest: crackles noted at left base

• Cardiovascular: regular rhythm, no murmur

• Extremities: scarring and erythema on both ankles consistent with resolving pyoderma gangrenosum

Laboratory

• Hgb 9.7 g/dL

• White Blood Cell Count 16.9 × 109/L

• Increased neutrophils on differential

• Electrolytes, creatinine, BUN and liver function tests within normal limits

Radiology

A portable AP of the chest was performed in the emergency department (Figure 1).

Figure 1. Portable AP of chest done in emergency department.

Which of the following are appropriate next step(s)? (Click on the correct answer to be directed to the second of six pages)

1. Thoracic CT scan

2. Discharge to home on empiric antibiotics with close follow-up

3. Influenza A/B, Covid and Cocci serology

4. 1 and 3

5. All of the above

Cite as: Wesselius LJ. June 2024 Pulmonary Case of the Month: A Pneumo-Colic Association. Southwest J Pulm Crit Care Sleep. 2024;28(6):74-77. doi: https://doi.org/10.13175/swjpccs023-24PDF

September 2023 Pulmonary Case of the Month: A Bone to Pick

Lewis J. Wesselius MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old man presented acute onset of shortness of breath. He denied cough, fever or other symptoms

Past Medical History, Family History and Social History

• Occasional gout
• No relevant family history
• Never smoked

Medications

• Allopurinol
• Multivitamin

Physical Examination

• Other than tachypnea and mild shortness of breath, no significant abnormalities.

Chest X-ray

An AP chest X-ray was performed (Figure 1).

Figure 1. Admission chest X-ray.

Which abnormality is suggested  by the chest X-ray? (Click on the correct answer to the second of seven pages)

1. Calcified micronodules in the right lung
2. Retained secretions with atelectasis left lung
3. Right pneumothorax
4. 1 and 3
5. None. The chest X-ray is within normal limits.

Cite as: Wesselius LJ. September 2023 Pulmonary Case of the Month: A Bone to Pick. Southwest J Pulm Crit Care Sleep. 2023;27(3):26-29. doi: https://doi.org/10.13175/swjpccs037-23 PDF

A Case of Progressive Bleomycin Lung Toxicity Refractory to Steroid Therapy

Christopher S Dossett MD¹, Kelli Kosako Yost MD¹, Christopher Lau MD², Nafis Shamsid-Deen MD²

¹Department of Internal Medicine, University of Arizona – Phoenix

²Department of Pulmonary and Critical Care Medicine, University of Arizona – Phoenix

Address: 475 N. 5th Street, Phoenix, Arizona, United States of America

Abstract

Bleomycin is a common chemotherapy agent used to treat germinative tumors. Bleomycin-induced lung injury (BILI) is an uncommon but devastating adverse effect of its use. It occurs in 10-20% of patients receiving bleomycin, and the initial diagnosis is usually made by new-onset respiratory symptoms and reduced diffusing capacity for carbon monoxide (DLCO). Mainstay treatment includes discontinuing bleomycin, corticosteroids, and supplemental oxygen if needed. We present a case of a 38-year-old male who was found to have a severe presentation of bleomycin-induced lung injury after chemotherapy for metastatic mixed germ cell testicular cancer. During his course, he was treated with the standard of care regimen of corticosteroids and salvage therapy with infliximab but ultimately died from complications of his illness. This case report is noteworthy because our patient had progressive bleomycin-induced lung injury, despite discontinuing bleomycin many months prior, consistent high-dose corticosteroid treatment, and even salvage therapy. In all patients on bleomycin, pulmonary function monitoring is essential, and any complaints of dyspnea should prompt concern for bleomycin-induced lung injury.  If initial treatment does not improve their condition, more aggressive measures may be necessary.

Abbreviations

• ARDS - acute respiratory distress syndrome
• BILI - bleomycin-induced lung injury
• CT - computed tomography
• DLCO - diffusing capacity for carbon monoxide
• ECMO - extracorporeal membrane oxygenation
• FDA - Food and Drug Administration
• IU - international units
• PFT - pulmonary function tests
• ROS - reactive oxygen species

Introduction

Bleomycin is an antibiotic used to treat germinative tumors and Hodgkin’s lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which occurs in up to 10-20% of patients receiving the drug, with mortality up to 1-2% (1). The primary mechanism is not entirely understood but is thought to be induced by the generation of reactive oxygen species (ROS) that form free radical oxidants (2). When type I pneumocytes experience oxidation from free radicals, they undergo apoptosis. This release of cellular contents can lead to the activation of neutrophils and pulmonary macrophages. These cells release cytokines and chemokines, which attract more inflammatory cells, amplifying the immune response. This ultimately disrupts the alveolar-capillary interface, causing capillary leak. This inflammation stimulates fibroblasts resulting in collagen deposits and irreversible pulmonary fibrosis.

The mainstay treatment of bleomycin-induced lung injury (BILI) involves discontinuing the medication and initiating corticosteroids to reduce inflammation (3). There has been limited updated evidence on managing BILI since White and Stover (3) in 1984 noted clinical improvement with corticosteroids. Only case series and reports have provided additional clinical experience on the efficacy of this treatment (4-7). As corticosteroids are helpful in acute BILI, patients with more indolent disease may benefit less. Recent case reports have trailed off-label therapies, including tumor necrosis alpha inhibitors, tyrosine kinase inhibitors, and antifibrotics, as potential treatment options with mixed results (8-12). Despite this well-known adverse effect of bleomycin, minimal evidence-based changes have been made in managing BILI, especially when refractory to corticosteroids. We present a case of a patient who developed rapidly progressive bleomycin-induced lung injury despite discontinuing bleomycin, initiation of high-dose corticosteroids, and salvage infliximab therapy.

Case Presentation

A 38-year-old man with a 10-pack-year tobacco use history and metastatic mixed germ cell testicular cancer undergoing bleomycin, etoposide, and cisplatin chemotherapy, with his last treatment a month prior, presented to a nearby emergency department with shortness of breath. He had completed four chemotherapy treatment cycles initiated three months earlier for a combined bleomycin dose of 330,000 IU (330 milligrams). Baseline pulmonary function test (PFT) before initiation of bleomycin showed a normal diffusing capacity for carbon monoxide (DLCO) at 90% of predicted. In the emergency department, he was found to be in respiratory failure with new onset ground-glass opacifications throughout bilateral lung fields by computed tomography (CT) angiogram (Figure 1).

Figure 1. Initial presentation CT pulmonary angiogram demonstrating ground-glass opacities present throughout both lungs. To view Figure 1 in a separate, enlarged window click here.

He denied using any vaping products. Infectious work-up was negative for SARS-CoV-2, influenza, and coccidiosis. He was treated for community-acquired pneumonia with an initial improvement of his respiratory failure and discharged a few days later on ambient air.

Despite oral antibiotic therapy and stopping cigarette use after discharge, the patient’s dyspnea and cough recurred less than a week after hospitalization. Repeat PFTs demonstrated new findings of reduced DLCO at 31% of predicted. Bleomycin was discontinued from his chemotherapy regimen due to concern of BILI. He was started on daily prednisone 60 mg, or approximately 1 mg/kg. He was tapered to 40 mg of prednisone daily over four weeks, but due to worsening dyspnea symptoms it had to be increased to 50 mg daily.

The patient re-presented to the emergency department one month after his initial hospitalization for acute on chronic shortness of breath and a persistent cough. Between these hospitalizations, the patient had not received etoposide or cisplatin treatment. His heart rate was 111 beats per minute, his respiratory rate was 16 breaths per minute, and his oxygen saturation was 95% at ambient air. Laboratory data was mainly unremarkable, except for a white blood cell count of 18.4 K/uL with neutrophilic predominance at 16.23 K/uL, hemoglobin 10.7 g/dL with an MCV of 103 fL, and C-reactive protein of 38.1 mg/L. A CT pulmonary angiogram demonstrated worsening interstitial and airspace opacities (Figure 2).

Figure 2. CT pulmonary angiogram shows significant interstitial and airspace opacity progression throughout the lungs. To view Figure 2 in a separate, enlarged window click here.

He was admitted and treated with broad-spectrum antibiotics due to concern of recurrent pneumonia, as he was not on antibiotic prophylaxis with his chronic steroids. The patient was resumed on his outpatient dose of oral prednisone 50 mg daily. Infectious work-up including blood, sputum, and fungal cultures, legionella antibodies, streptococcus pneumonia urinary antigen, mycoplasma antibodies, aspergillus, fungitell, coccidioides serologies, HIV, and viral etiologies including SARS-CoV-2, influenza, and cytomegalovirus were all unremarkable. Due to a broad negative infectious work-up, BILI was highly thought to be the original diagnosis. He was switched to intravenous methylprednisolone 60 mg every 12 hours for more aggressive BILI treatment.

Two days after admission, he became acutely dyspneic. A repeat chest radiographic demonstrated continued bilateral airspace opacities with new moderate to large right apical pneumothorax. He underwent CT-guided right thoracostomy tube placement for the new pneumothorax. His respiratory status deteriorated over the next five days requiring endotracheal intubation. Bronchoalveolar lavage performed during intubation was unremarkable for infectious etiologies or malignant cells. Due to continued deterioration, his methylprednisolone was increased to 250 mg every 6 hours. Six days after intubation, he had minimal improvement, so salvage therapy with 300 mg of infliximab was initiated. The patient had worsening oxygenation despite mechanical ventilation. Ventilation strategies were also limited due to high peak inspiratory pressures.

Repeat CT chest without contrast demonstrated worsening extensive interstitial and airspace opacities throughout bilateral lungs (Figure 3).

Figure 3. CT chest without contrast after an acute respiratory decompensation demonstrated persistent interstitial and airspace opacities throughout bilateral lungs, significantly worse than the prior CT. To view Figure 3 in a separate, enlarged window click here.

With minimal improvement in his respiratory failure, the patient was transferred to a university hospital to initiate inhaled prostacyclin therapy in an attempt to improve oxygenation and ventilation. He was started on inhaled epoprostenol and cisatracurium infusion. Despite these measures, the patient had no improvement in his respiratory failure with persistent extensive interstitial and airspace opacities throughout bilateral lungs on repeat CT (Figure 4).

Figure 4. CT pulmonary angiogram showing persistent extensive bilateral ground-glass opacities, scattered consolidative opacities, bronchiectasis, and new pneumomediastinum. To view Figure 4 in a separate, enlarged window click here.

Extracorporeal membrane oxygenation (ECMO) was considered, but he was deemed not an appropriate candidate given the irreversible lung injury. With all avenues for recovery exhausted, the poor prognosis was discussed with the family, who decided to transition to comfort-only care. He expired shortly after cessation of aggressive life support measures.

Discussion

Bleomycin-induced lung injury (BILI) is thought to be due to the development of pulmonary fibrosis, characterized by enhanced production and deposition of collagen and other matrix components (1). Pulmonary toxicity is dose-dependent, with most of these injuries occurring with doses above 400,000 IU. Other risk factors include kidney dysfunction, older age, supplemental oxygen exposure, bolus delivery of infusion, extent of lung metastases, and established lung disease (13). Symptoms and signs include nonproductive cough, dyspnea, pleuritic or substernal chest pain, fever, tachypnea, crackles, lung restriction, and hypoxemia. Clinical manifestations usually develop indolently between one and six months after treatment initiation, but they may persist more than six months after treatment discontinuation. The earliest manifestation of BILI is dyspnea with a reduction in the DLCO (14-15). Best-practice clinical guidelines and the U.S. Food and Drug Administration (FDA) recommend PFTs at baseline and monthly or after each new treatment cycle (16). A DLCO reduction of more than 30-35% should prompt providers to discontinue bleomycin, even if asymptomatic, due to the concern of BILI. However, a recent randomized phase III trial demonstrated that the presence of cough had a higher association with BILI than PFT changes, questioning the benefit of routine PFTs (17).

BILI treatment involves prompt discontinuation of all chemotherapeutic agents. Corticosteroids are given to patients with symptomatic lung toxicity. The suggested prednisone dosing is 0.75 to 1 mg/kg (based on ideal body weight) per day, to a maximum of 100 mg/day, for the first four to six weeks based on clinical data and case reports (3-7). Clinical and radiographic improvement varies by report from 7 to 12 days after early initiation of high-dose corticosteroid therapy (6). There have been two fatal cases of BILI that were attributed to insufficient corticosteroid doses (18). This emphasizes the need for a higher dose to treat the condition effectively. Most patients respond after treatment with limited case reports discussing corticosteroid refractory BILI. These cases have led to the evaluation of off-label therapies as potential treatments. Recent case reports have described imatinib, infliximab, and pirfenidone to have variable success in treating BILI, including those cases refractory to corticosteroids; however, these require long treatment durations for clinical success (8-12).

Etoposide and bleomycin can both cause lung injury; however, the two drugs' mechanisms of injury and clinical presentations can differ (19). Etoposide-induced lung injury typically presents as acute respiratory distress syndrome (ARDS) within hours to days of exposure. In contrast, BILI typically presents as a more gradual onset of pulmonary fibrosis, which can occur weeks to months after exposure. Our patient's clinical course was indolent after discontinuing his chemotherapeutics which is more consistent with a BILI presentation. However, it is difficult to say with the utmost certainty that our patient’s lung injury was not worsened by etoposide.

We present an unusual case of corticosteroid refractory BILI in a young patient with minimal tobacco history and no end-organ dysfunctions. Given the enormous respiratory reserve, most young, healthy patients will develop symptoms only after a severe reduction in diffusion. Our patient did not have the recommended interval PFT monitoring described by clinical guidelines and the FDA. This highlights the importance of interval monitoring, including symptomatic tracking, especially in young patients, in the hopes of early diagnosis of BILI. As this disease usually progresses indolently, monthly PFTs can capture the subtle advancement of lung injury in younger patients. It is uncertain when the initial lung injury began in our patient due to a lack of PFT monitoring during the four treatment cycles of bleomycin. However, if changes had been detected, earlier management could have been implemented, such as earlier discontinuation of chemotherapy, increasing corticosteroids, or off-label therapies.

This case also accentuates the limited data on off-label treatment options for corticosteroid refractory BILI. Our patient developed progressive pulmonary fibrosis, ultimately leading to his demise. Although he received infliximab as salvage therapy, it is improbable that this treatment would have had benefit due to the late fibrosing stage of his disease presentation. Universally, an immunomodulatory agent’s efficacy wanes dramatically once in the terminal fibrosing stages of many interstitial lung diseases, reiterating the need for early diagnosis and aggressive treatment during the inflammatory phase (20). If our patient had been identified sooner as refractory to corticosteroids, prompter introduction of second-line agents might have resulted in an alternative clinical outcome. Maximizing medical management in this patient population is particularly critical given that other salvage treatments like ECMO and lung transplantation are not recommended and are usually contraindicated. Additional prospective investigation in refractory disease is necessary to better validate and quantify the therapeutic efficacy of available second-line and off-line medical therapies.

Conclusion

Patients on bleomycin therapy are at risk of developing BILI associated dyspnea that may present as progressive pulmonary fibrosis, hypersensitivity pneumonitis, or organizing pneumonia. If a patient treated with bleomycin continues to have unremitting shortness of breath, the concern for BILI should be high and may warrant earlier evaluation and intervention.

Acknowledgments

Christopher S Dossett, Kelli Kosako Yost, Christopher Lau, and Nafis Shamsid-Deen contributed to the drafting and revising of this manuscript. The authors have no conflict of interest. All authors have consented to the approval of this manuscript.

References

1. Reinert T, Baldotto C, Nunes F, Scheliga A. Bleomycin-Induced Lung Injury. Journal of Cancer Research 2013;2013:1-9. [CrossRef]
2. Hay J, Shahzeidi S, Laurent G. Mechanisms of bleomycin-induced lung damage. Arch Toxicol. 1991;65(2):81-94. [CrossRef] [PubMed]
3. White DA, Stover DE. Severe bleomycin-induced pneumonitis. Clinical features and response to corticosteroids. Chest. 1984 Nov;86(5):723-8. [CrossRef] [PubMed]
4. Ghalamkari M, Khatuni M, Toogeh G, Haghighi S, Taherkhani M. Reversible Acute Lung Injury due to Bleomycin. Tanaffos. 2022 Feb;21(2):253-256. [PubMed]
5. Rashid RS. Bleomycin lung: a case report. BMJ Case Rep. 2009;2009:bcr11.2008.1175. [CrossRef] [PubMed]
6. Gupta R, Ettinger NA. Beyond conventional therapy: role of pulse steroids in bleomycin induced lung injury. Respir Care. 2014 Jan;59(1):e9-e12. [CrossRef] [PubMed]
7. Wang, X, Deng, J, Sothwal, A, Gordon, E, Patel, G. Bleomycin-Induced Pneumonitis Responds To Super-High-Dose Steroid and Monitored By LDH and PAO2/FIO2.  Critical Care Medicine 2016;44(12):558. [CrossRef]
8. Banakh I, Lam A, Tiruvoipati R, Carney I, Botha J. Imatinib for bleomycin induced pulmonary toxicity: a case report and evidence-base review. Clin Case Rep. 2016 Apr 1;4(5):486-90. [CrossRef] [PubMed]
9. Ge V, Banakh I, Tiruvoipati R, Haji K. Bleomycin-induced pulmonary toxicity and treatment with infliximab: A case report. Clin Case Rep. 2018 Sep 4;6(10):2011-2014. [CrossRef] [PubMed]
10. Carnevale-Schianca F, Gallo S, Rota-Scalabrini D, Sangiolo D, Fizzotti M, Caravelli D, Capaldi A, Anselmetti G, Palesandro E, D'Ambrosio L, Coha V, Obert R, Aglietta M, Grignani G. Complete resolution of life-threatening bleomycin-induced pneumonitis after treatment with imatinib mesylate in a patient with Hodgkin's lymphoma: hope for severe chemotherapy-induced toxicity? J Clin Oncol. 2011 Aug 20;29(24):e691-3. [CrossRef] [PubMed]
11. Aykaç N, Tecimer C. Imatinib Treatment for Bleomycin-Induced Pulmonary Toxicity. Turk Thorac J. 2020 Nov;21(6):457-460. [CrossRef] [PubMed]
12. Sakamoto K, Ito S, Hashimoto N, Hasegawa Y. Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma. BMC Cancer. 2017 Aug 7;17(1):526. [CrossRef] [PubMed]
13. Comis RL. Bleomycin pulmonary toxicity: current status and future directions. Semin Oncol. 1992 Apr;19(2 Suppl 5):64-70. [PubMed]
14. Lucraft HH, Wilkinson PM, Stretton TB, Read G. Role of pulmonary function tests in the prevention of bleomycin pulmonary toxicity during chemotherapy for metastatic testicular teratoma. Eur J Cancer Clin Oncol. 1982 Feb;18(2):133-9. [CrossRef] [PubMed]
15. Nippon Kayaku Co., Ltd. Blenoxane (bleomycin sulfate) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf. Revised April 2010. Accessed April 15, 2023.
16. Watson RA, De La Peña H, et al. Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK. Br J Cancer. 2018 Oct;119(9):1044-1051. [CrossRef] [PubMed]
17. Shamash J, Sarker SJ, Huddart R, et al. A randomized phase III study of 72 h infusional versus bolus bleomycin in BEP (bleomycin, etoposide and cisplatin) chemotherapy to treat IGCCCG good prognosis metastatic germ cell tumours (TE-3). Ann Oncol. 2017 Jun 1;28(6):1333-1338. [CrossRef] [PubMed]
18. Bloor AJ, Seale JR, Marcus RE. Two cases of fatal bleomycin pneumonitis complicating the treatment of non-Hodgkin's lymphoma. Clin Lab Haematol. 1998 Apr;20(2):119-21. [CrossRef] [PubMed]
19. Gurjal A, An T, Valdivieso M, Kalemkerian GP. Etoposide-induced pulmonary toxicity. Lung Cancer. 1999 Nov;26(2):109-12. [CrossRef] [PubMed]
20. Davies HR, Richeldi L, Walters EH. Immunomodulatory agents for idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2003;(3):CD003134. [CrossRef] [PubMed]

Cite as: Dossett CS, Yost KK, Lau C, Shamsid-Deen N. A case of progressive bleomycin lung toxicity refractory to steroid therapy. Southwest J Pulm Crit Care Sleep. 2023;26(6):90-96. doi: https://doi.org/10.13175/swjpccs013-23 PDF

December 2022 Pulmonary Case of the Month: New Therapy for Mediastinal Disease

Lewis J. Wesselius MD

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 43-year-old woman complained of persistent cough over 1 year with mild increasing dyspnea on exertion. She denied fever, sweats or weight loss. She had noted fatigue and dry cough, as well as shortness of breath, particularly when supine.

Past Medical History (PMH), Social History (SH), Family History (FH)

• An outside bronchoscopy done in 2019 with washings and biopsy showing only some non-specific inflammation
• Life-long nonsmoker
• Not on any chronic medications
• Had only lived in Arizona, although has travelled in other states
• There is no significant family history

Physical Examination

• Prominent vascularity on anterior chest

What should be done at this time? (Click on the correct answer to be directed to the 2nd of 6 pages)

1. Chest X-ray
2. Obtain old x-rays
3. Pulmonary function testing
4. Serology for coccidioidomycosis
5. All of the above

Cite as: Wesselius LJ. December 2022 Pulmonary Case of the Month: New Therapy for Mediastinal Disease. 2022;25(6):92-96. doi: https://doi.org/10.13175/swjpccs054-22 PDF

Kaposi Sarcoma With Bilateral Chylothorax Responsive to Octreotide

Humzah Iqbal, MD

Department of Internal Medicine, University of California San Francisco, Fresno, CA, USA

Abstract

Kaposi sarcoma (KS) is a soft tissue malignancy of the endothelial cells that can rarely invade the thoracic duct and cause bilateral chylothorax. Treatment for chylothorax includes drainage and dietary modification. However, octreotide has been reported to improve chylothorax in some pediatric and post-operative cases. We present a case in which a 9-day course of octreotide led to an improvement of non-traumatic malignant chylothorax.

Abbreviation list

• AIDS: acquired immunodeficiency syndrome
• CT: computed tomography
• HIV: human immunodeficiency virus
• KS: Kaposi sarcoma

Introduction

Kaposi sarcoma (KS) is a malignant, multifocal, highly vascularized tumor of the endothelial cells that most commonly affects the skin but may also include the lymph nodes, mucosa, and viscera (1). KS is commonly associated with human immunodeficiency virus (HIV) and can occur at any CD4 count (2). In very rare cases, Kaposi sarcoma can invade the thoracic duct and cause chylothorax (3). Chylothorax occurs when lymphatic fluid accumulates in the pleural cavity and is usually seen after damage to the thoracic duct following trauma or cardiothoracic surgery. It can also be caused by malignancy, however, bilateral chylothorax secondary to KS is rare. Treatment of chylothorax usually involves drainage of the effusion and initiation of a low-fat diet. Octreotide has been reported to improve traumatic chylothorax, but has only been reported in non-traumatic etiologies in a handful of cases (4). Here, we present a case of bilateral chylothorax associated with KS, which was successfully treated with octreotide.

Case Presentation 

A 40-year-old man with a previous diagnosis of acquired immunodeficiency syndrome (AIDS) and KS presented to the emergency department due to progressive tachypnea, dyspnea, bilateral lower extremity edema, and expansion of his KS lesions onto his legs and genital region. His vital signs were significant for a respiratory rate of 25 breaths per minute and pulse of 109 beats per minute. The patient denied recent infection, trauma, or procedures. Chest X-ray showed a large left pleural effusion with midline shift and a small right pleural effusion (Figure 1).

Figure 1. Upright chest X-ray demonstrating large left pleural effusion with midline shift and small right pleural effusion.

Computed tomography (CT) scan of the chest showed large bilateral pleural effusions with collapse of the right lower lobe and partial collapse of the upper lobes bilaterally (Figure 2).

Figure 2. Representative view from computed tomography (CT) scan (axial plane) in lung windows showing bilateral pleural effusions.

The patient developed hypoxemia and underwent thoracentesis with a total of 1.5 liters of pink, milky fluid removed (Figure 3).

Figure 3. Image of pleural fluid obtained from thoracentesis demonstrating pink, milky appearance.

Bilateral PleurX catheters (PleurX; Iskus Health; London, United Kingdom) were placed for persistent drainage. Fluid studies showed a triglyceride count of 147 mg/dL on the right side and 153 mg/dL on the left side. The patient continued to self-drain when symptomatic and drained about 600 mL of light-colored opaque fluid from each side daily. Serum albumin levels decreased to about 2.0 g/dL over the next week with concurrent development of diffuse pitting edema in all four extremities and abdomen. He was started on a high-protein, low-fat diet consuming up to 6-7 nutritional protein supplements per day with little to no improvement in his clinical state or serum protein levels. Given the patient’s poor response to treatment and persistence of his pleural effusions, a trial of octreotide was initiated. The patient was given octreotide 100 mg three times per day. About 3 days after initiating therapy, the patient refrained from draining his PleurX catheters for the first time and the frequency of draining decreased over the remainder of the week due to improvement in symptoms. The fluid was noted to be less opaque and clearer with each drainage. The patient’s tachypnea and oxygen saturation also showed improvement. After day 9 of octreotide, the treatment was discontinued and repeat pleural fluid studies showed a triglyceride count of 69 mg/dL on the right side and 89 mg/dL on the left side. With the resolution of his chylothorax and improvement in oxygenation status as well as his edema, the patient was discharged and will follow up with Oncology for continuation of his KS treatment.

Discussion

KS is known as an AIDS-defining illness that can invade a variety of tissues in the body leading to manifestations beyond the classic skin lesions. It can cause unusual neurologic, cardiac, orbital, laryngeal, endocrine, and gastrointestinal complications in rare cases (5). We present a case of bilateral chylothorax as another rare potential complication of KS. Other reported cases have presented similarly to our patient, such as a case presented by Pennington et al. (6) which also described dyspnea and hypoxemia with transient but significant improvements in ventilation with serial chest drainage as well as repeated reaccumulation of the chylothorax. In their case, however, the patient died as a result of his condition. Other cases of presumed KS-induced chylothorax have also resulted in marked nutritional deficiencies as seen in our patient (7).

Treatment of chylothorax involves therapeutic thoracentesis, a low-fat diet that is high in medium-chain triglycerides which do not pass through the thoracic duct, and surgical correction or embolization of the defect (8). Though not a standard practice, the use of octreotide has been reported to improve chylothorax in some cases. The majority of these cases have been traumatic chylothorax following cardiothoracic surgery in adults or the pediatric population, or neonates with congenital chylothorax (8). There is a paucity of literature regarding octreotide in the management of malignant and other non-traumatic causes of chylothorax in the adult population. One case has been reported by Togashi et al. (9) which describes chylothorax secondary to idiopathic fibrosing mediastinitis that was treated successfully with octreotide. The exact mechanism is unknown, but as a somatostatin analogue, it may involve a decrease in splanchnic blood flow and subsequent reduction in lymphatic flow from the gastrointestinal system and through the thoracic duct (10-11). There is no standard protocol for the administration of octreotide, however, most studies report a 1-2 week course with recognizable improvements after 2-3 days of treatment, as seen in our patient (12).

Conclusion

Bilateral chylothorax is a rare manifestation of KS that can lead to respiratory failure, malnutrition, and death. We present a case of non-traumatic, malignant chylothorax that was treated successfully with octreotide, a somatostatin analogue. Further studies are necessary to elucidate the exact mechanism of its effect on chylothorax and to establish a standardized treatment protocol for the usage of octreotide in this condition. 

References

1. Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. Kaposi sarcoma. Nat Rev Dis Primers. 2019 Jan 31;5(1):9. [CrossRef] [PubMed]
2. Crum-Cianflone NF, Hullsiek KH, Ganesan A, Weintrob A, Okulicz JF, Agan BK; Infectious Disease Clinical Research Program HIV Working Group. Is Kaposi's sarcoma occurring at higher CD4 cell counts over the course of the HIV epidemic? AIDS. 2010 Nov 27;24(18):2881-3. [CrossRef] [PubMed]
3. Cherian S, Umerah OM, Tufail M, Panchal RK. Chylothorax in a patient with HIV-related Kaposi's sarcoma. BMJ Case Rep. 2019 Jan 22;12(1):e227641. [CrossRef] [PubMed]
4. Ismail NA, Gordon J, Dunning J. The use of octreotide in the treatment of chylothorax following cardiothoracic surgery. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):848-54. [CrossRef] [PubMed]
5. Pantanowitz L, Dezube BJ. Kaposi sarcoma in unusual locations. BMC Cancer. 2008 Jul 7;8:190. [CrossRef] [PubMed]
6. Pennington DW, Warnock ML, Stulbarg MS. Chylothorax and respiratory failure in Kaposi's sarcoma. West J Med. 1990 Apr;152(4):421-2. [PubMed]
7. Judson MA, Postic B. Chylothorax in a patient with AIDS and Kaposi's sarcoma. South Med J. 1990 Mar;83(3):322-4. [CrossRef] [PubMed]
8. Schild HH, Strassburg CP, Welz A, Kalff J. Treatment options in patients with chylothorax. Dtsch Arztebl Int. 2013 Nov 29;110(48):819-26. doi: 10.3238/arztebl.2013.0819. [CrossRef] [PubMed]
9. Togashi Y, Kim YH, Miyahara R, et al. Octreotide, a somatostatin analogue, in the treatment of chylothorax associated with idiopathic fibrosing mediastinitis. Tohoku J Exp Med. 2010 Sep;222(1):51-3. [CrossRef] [PubMed]
10. Katz MD, Erstad BL. Octreotide, a new somatostatin analogue. Clin Pharm. 1989 Apr;8(4):255-73. [PubMed]
11. Rosti L, De Battisti F, Butera G, et al. Octreotide in the management of postoperative chylothorax. Pediatr Cardiol. 2005 Jul-Aug;26(4):440-3. [CrossRef] [PubMed]
12. Kalomenidis I. Octreotide and chylothorax. Curr Opin Pulm Med. 2006 Jul;12(4):264-7. [CrossRef] [PubMed]

Cite as: Iqbal H. Kaposi Sarcoma With Bilateral Chylothorax Responsive to Octreotide. Southwest J Pulm Crit Care Sleep. 2022;25(5):69-72. doi: https://doi.org/10.13175/swjpccs048-22 PDF

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 

June 2022 Pulmonary Case of the Month: A Hard Nut to Crack

Daniel Gergen MD¹

Anne Reihman MD¹

Carolyn Welsh MD^1,2

¹Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Colorado, Aurora, Colorado USA

²Eastern Colorado Veterans Affairs Medical Center, Aurora, Colorado USA

History of Present Illness: A 54-year-old man presented to clinic with chronic cough, dyspnea on exertion, unintentional weight loss, and night sweats. Seven months before, he developed dyspnea on exertion and symptoms did not improve with inhalers. Four months prior to presentation, he was treated for presumed community-acquired pneumonia of the right lower lobe. Neither symptoms nor chest radiograph improved with multiple courses of antibiotics. In the four weeks prior to presentation his symptoms progressed to the point that he was unable to walk in his house without significant dyspnea.

Review of systems: 10-pound unintentional weight loss and six weeks of night sweats.

Past Medical History, Social History and Family History: The patient had a 15-pack-year smoking history and quit 15 years prior to presentation. He had no other past medical history, surgical history, family history, nor medications.

Physical Examination: Vital signs were normal on presentation. Physical exam showed faint wheezing and decreased breath sounds over the right posterior lung fields.

Radiography: Chest radiograph demonstrated dense opacification in the superior segment of the right lower lobe (Figure 1).

Figure 1. Initial chest radiography. A: PA view. B: Lateral view.

What are diagnostic possibilities at this time?

1. Lung abscess
2. Lung cancer
3. Foreign body with post-obstructive pneumonia
4. Tuberculosis
5. 1 and 3
6. All the above

Cite as: Gergen D, Reihman A, Welsh C. June 2022 Pulmonary Case of the Month: A Hard Nut to Crack. Southwest J Pulm Crit Care Sleep. 2022;24(6):89-92. doi: https://doi.org/10.13175/swjpccs024-22 PDF

Diagnostic Challenges of Acute Eosinophilic Pneumonia Post Naltrexone Injection Presenting During The COVID-19 Pandemic

Michelle Breuer

Abdulmonam Ali, MD

SSM Health

Mount Vernon, IL USA

Introduction

Acute eosinophilic pneumonia (AEP) is a rare respiratory illness that may present with nonspecific symptoms ranging in severity from cough and dyspnea to potentially fatal acute respiratory distress syndrome. Although the exact etiology of AEP is unknown, it is thought to be a hypersensitivity reaction that can be idiopathic or caused by various infections, inhalation exposures, and medications (1).  Here we present a rare case of AEP secondary to injectable naltrexone.

Case Presentation

A 45-year-old Caucasian male with a history of alcohol use disorder presented to the emergency room with a 3-day history of progressively worsening dyspnea and dry cough. The patient was a lifelong non-smoker with an unremarkable past medical history aside from alcohol abuse and obesity (BMI 41.64 kg/m²). He denied fever or chills, orthopnea, chest pain, or symptoms suggestive of paroxysmal nocturnal dyspnea. He also denied any recent sick contacts, including exposure to COVID-19. Relevant history includes alcohol cessation 1 month before presentation. After 2 weeks of cessation, he received his first injection of naltrexone (Vivitrol®) as part of alcohol relapse prevention. Physical exam was notable for an initial SpO₂ of 69% on room air, sinus tachycardia at a rate of 121 bpm, and obesity. Chest examination exhibited decreased air entry with bilateral fine crackles on auscultation. No skin rashes or peripheral edema were appreciated, and the remaining physical exam was within normal limits. The patient was started on supplemental oxygen (6 liters/minute nasal cannula to maintain SpO2 above 90%).

Workup was performed and chest x-ray showed diffuse bilateral pulmonary infiltrates (Figure 1), hence, the patient was started on empiric antibiotic and steroid therapy.

Figure 1. Chest X-ray showing bilateral ground-glass opacities.

SARS-CoV-2 PCR testing was performed twice due to high clinical suspicion of COVID-19 infection (the patient was seen during the Coronavirus pandemic). Both SARS-CoV-2 tests were negative as well as the rest of the respiratory viral panel. CBC was significant for leukocytosis with an absolute peripheral eosinophil count of 0.49 x 10⁹ cells/L. Bloodwork also revealed mildly elevated troponin, d-dimer, and LDH. However, electrocardiogram showed no significant ST changes and Computerized Tomography (CT) angiography chest showed no evidence of pulmonary embolism but confirmed the chest x-ray findings of diffuse bilateral ground-glass opacities with anterolateral subpleural parenchymal sparing (Figure 2).

Figure 2. CTA chest (axial view, lung window) showing diffuse ground-glass opacities.

An echocardiogram showed an ejection fraction of 60% and normal left ventricular diastolic function. Moderate right ventricular (RV) dilation with reduced systolic function was reported and the peak RV pressure was estimated at 39 mmHg. Extensive blood testing for connective tissue disease was negative for ANCA, CCP, ANA, and cryoglobulins. Immunoglobulin E (IgE) level was within normal limits at 14KU/L (reference range < 214 KU/L).  Infectious disease serology was negative for mycoplasma, strongyloides, coccidioides, and aspergillus. HIV and hepatitis screening were also negative. Bronchoscopy with bronchoalveolar lavage (BAL) was performed and was significant for 27% eosinophils, 42% lymphocytes, 25% monocytes, 6% neutrophils (Figure 3).

Figure 3. Bronchoalveolar lavage (BAL) showing increased numbers of eosinophils.

BAL culture remained negative including mycobacterial and fungal cultures. BAL testing for Pneumocystis Jirovecii was negative as well. BAL cytology showed benign bronchial epithelial cells and inflammatory cells. No parasites were seen in BAL and fungal staining was negative.

The constellation of the above clinical, radiological, and laboratory findings was highly suggestive of acute eosinophilic pneumonia diagnosis. The patient’s methylprednisolone dose was increased to 125mg every 8 hours. Due to high FiO2 requirements and poor pulmonary reserve, the patient remained intubated after his bronchoscopy procedure. Over the following 48 hours, FiO₂ requirements improved significantly and his repeat chest x-ray showed almost complete resolution of the pulmonary infiltrates. The patient was successfully extubated to 2 liters of oxygen via nasal cannula on the third day.  Supplemental oxygen was eventually weaned off to room air. There wasn’t significant desaturation observed with the exercise trial. He was discharged home on a gradually tapering dose of oral steroids over 6 weeks. The patient was later seen at the pulmonary clinic for a follow-up visit. He was doing well and denied any significant respiratory symptoms. A follow-up chest x-ray was within normal limits (Figure 4).

Figure 4. Chest x-ray upon follow-up.

Discussion 

Acute eosinophilic pneumonia (AEP) is defined by rapid eosinophilic infiltration of the lung tissue, resulting in impaired gas exchange. Presenting symptoms are nonspecific and may include cough, progressive dyspnea, chest pain, and fever (2). Chest imaging of patients with AEP shows diffuse bilateral parenchymal infiltrates. Diagnosis can be made in the appropriate clinical and radiological context, with BAL showing at least 25% eosinophils on the fluid differential, and with no other identifiable causes (1).

The pathogenesis of AEP is not completely understood; however, it is hypothesized to involve a hypersensitivity reaction in patients with genetic susceptibility (3,4). AEP can be associated with many identifiable causes including cigarette smoke most notably, as well as other inhalants, infections, and medications. Although antibiotics and nonsteroidal anti-inflammatory drugs are among the more common inciting medications, injectable naltrexone has been implicated in several case reports (3,5,6,7).

The clinical presentations of AEP can mimic SARS-CoV-2 pneumonia, community-acquired pneumonia, or ARDS; hence, a high index of clinical suspicion is essential to avoid delay in therapy. A confident diagnosis of AEP can usually be made without a lung biopsy in patients who meet the following criteria (8):

1) acute onset of febrile respiratory manifestations (≤ 1-month duration before consultation).

2) bilateral diffuse opacities on chest radiography.

3) hypoxemia, with PaO₂ on room air<60 mm Hg, and/or PaO₂/FiO₂≤300 mm Hg, and/or oxygen saturation on room air<90%.4) lung eosinophilia, with >25% eosinophils on BAL differential cell count (or eosinophilic pneumonia at lung biopsy).

5) absence of known causes of AEP, including drugs, infections, asthma, or atopic disease.

In our case, the patient has met most of the suggested criteria for diagnosing AEP in addition to the presence of a triggering factor (a clear temporal relationship between the development of symptoms and the recent naltrexone injection). However, we met with a few obstacles before making the diagnosis of AEP.  During these unprecedented times, any patient presenting with acute hypoxic respiratory failure, and/or ground-glass opacities (both are classic for SARS-CoV-2 pneumonia as well as AEP) must go through an additional screening process to rule out COVID-19, including contact and airborne infection isolation precautions in addition to the standard precautions and SARS-CoV-2 PCR testing.  

On the other hand, several recent reports of AEP presumably triggered by SARS-CoV-2 infection had been described (9-10), which was another factor that contributed to making the diagnosis of AEP more challenging in his case and kept COVID-19 high on the differential diagnosis list. Furthermore, our patient received steroids on the initial presentation which likely affected the accuracy of the total eosinophilic counts in the BAL.

AEP has a higher likelihood than chronic eosinophil pneumonia of presenting with more severe symptoms and has a greater potential of rapid progression to respiratory failure. One review study reported 30-80% of AEP patients required intensive care unit admission and another case review noted 20% of AEP patients required mechanical ventilation (4,11). Treatment includes supportive care, recognition and avoidance of identifiable triggers, and systemic corticosteroids. Most patients rapidly improve with prompt corticosteroid treatment and experience complete recovery (1,3). Relapse of AEP rarely occurs (4).

Numerous conditions can cause pulmonary eosinophilia that needs to be differentiated from AEP. Different classifications have been suggested, but we will list the broad categories and most common etiologies including chronic eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis (EGPA, previously known as Churg-Strauss), drug and toxin-induced eosinophilic lung disease, helminthic, and fungal infection-related eosinophilic lung diseases, idiopathic hypereosinophilic syndrome, neoplasms, interstitial lung disease, coccidioidomycosis, tuberculosis, and allergic bronchopulmonary aspergillosis.

In addition to AEP, several conditions are associated with elevated BAL eosinophils greater than 25%.  These conditions include chronic eosinophilic pneumonia, EGPA, tropical pulmonary eosinophilia.  Other conditions causing BAL eosinophilia, but less than 25%, include connective tissue disease, drug-induced pneumonitis, fungal pneumonia, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, sarcoidosis.

Finally, multiple medications are implicated in drug-induced AEP, however, naltrexone is still not well recognized as a potential cause.  In a recent retrospective review, naltrexone was not included in the medication list compiled (11).

Conclusion

Injectable naltrexone, a long-acting opioid antagonist, is used for the treatment of opioid and alcohol dependence. Although rare, the use of injectable naltrexone is associated with the potentially fatal side effect of AEP. Since AEP shares many clinical attributes with other causes of acute lung injury, including community-acquired pneumonia and SARS-CoV-2 pneumonia, it can be easily overlooked. Therefore, having an accurate history and an appropriate index of suspicion is important for early detection and proper management (3).

References

1. De Giacomi F, Vassallo R, Yi ES, Ryu JH. Acute Eosinophilic Pneumonia. Causes, Diagnosis, and Management. Am J Respir Crit Care Med. 2018 Mar 15;197(6):728-736. [CrossRef] [PubMed]
2. Katz U, Shoenfeld Y. Pulmonary eosinophilia. Clin Rev Allergy Immunol. 2008 Jun;34(3):367-71. [CrossRef] [PubMed]
3. Mears M, McCoy K, Qiao X. Eosinophilic Pneumonia and Extended-Release Injectable Naltrexone. Chest. 2021;160(4): A1676 [Abstract]. [CrossRef]
4. Suzuki Y, Suda T. Eosinophilic pneumonia: A review of the previous literature, causes, diagnosis, and management. Allergol Int. 2019 Oct;68(4):413-419. [CrossRef] [PubMed]
5. Horsley R, Wesselius LJ. June 2107 Pulmonary Case of the Month. Southwest J Pulm Crit Care. 2017;14(6):255-61. [CrossRef]  
6. Esposito A, Lau B. Saved by the BAL: A Case of Acute Eosinophilic Pneumonia After Methyl-Naltrexone Injection. Chest. 2019;156(4):A2210 [Abstract]. [CrossRef]
7. Korpole PR, Al-Bacha S, Hamadeh S. A Case for Biopsy: Injectable Naltrexone-Induced Acute Eosinophilic Pneumonia. Cureus. 2020 Sep 3;12(9):e10221. [CrossRef] [PubMed]
8. Philit F, Etienne-Mastroïanni B, Parrot A, Guérin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med. 2002 Nov 1;166(9):1235-9. [CrossRef] [PubMed]
9. Araújo M, Correia S, Lima AL, Costa M, Neves I. SARS-CoV-2 as a trigger of eosinophilic pneumonia. Pulmonology. 2022 Jan-Feb;28(1):62-64. [CrossRef] [PubMed]
10. Murao K, Saito A, Kuronuma K, Fujiya Y, Takahashi S, Chiba H. Acute eosinophilic pneumonia accompanied with COVID-19: a case report. Respirol Case Rep. 2020 Nov 16;8(9):e00683. [CrossRef] [PubMed]
11. Bartal C, Sagy I, Barski L. Drug-induced eosinophilic pneumonia: A review of 196 case reports. Medicine (Baltimore). 2018 Jan;97(4):e9688. [CrossRef] [PubMed]
12. Salahuddin M, Anjum F, Cherian SV. Pulmonary Eosinophilia. 2021 Dec 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. [PubMed]

Cite as: Breuer M, Ali A. Diagnostic Challenges of Acute Eosinophilic Pneumonia Post Naltrexone Injection Presenting During The COVID-19 Pandemic. Southwest J Pulm Crit Care Sleep. 2022;24(2):26-31. doi: https://doi.org/10.13175/swjpccs002-22 PDF 

Symptomatic Improvement in Cicatricial Pemphigoid of the Trachea Achieved with Laser Ablation Bronchoscopy

Elizabeth Benge MD¹, Vincent Tran MD², Nazanin Sheikhan MD¹, Sapna Bhatia MD³, Yi McWhorter DO⁴, John Collier MD³, Arnold Chung MD⁵

Departments of ¹Internal Medicine, ²Surgery, ³Pulmonology, ⁴Anesthesiology/Critical Care Medicine, and ⁵MountainView Cardiovascular and Thoracic Surgery Associates

HCA Healthcare MountainView Hospital 

Las Vegas, NV, USA 

Abstract

Cicatricial pemphigoid (CP) with tracheal involvement is a rare and potentially deadly condition. Here, we report the first case in which Nd:YAG laser (1064nm) laser ablation bronchoscopy was used to treat CP with tracheal involvement. Our patient is a 71-year-old male with a history of CP refractory to medical therapy affecting his trachea who presented to the emergency department with dyspnea. He ultimately underwent bronchoscopy with Nd: YAG laser (1064nm) laser ablation, which resulted in a temporary alleviation of his respiratory symptoms. A repeat laser ablation was planned in hopes of prolonging the patient’s remission, but due to interval changes in the patient’s airway anatomy, it was deemed unsafe. While our patient’s uniquely advanced disease was not amenable to further laser-mediated intervention, it is possible that patients with less advanced disease may experience better outcomes with similar therapy. This case shows the promise laser ablation could hold for patients with tracheal cicatricial pemphigoid.

Introduction

Cicatricial pemphigoid (CP) is a diverse group of subepithelial blistering disorders of the skin and mucous membranes (1,2). Tracheal involvement is a rare and deadly sequela of this disease class (3). We report the first case in which Nd:YAG laser (1064nm) laser ablation bronchoscopy was used as a treatment for CP with tracheal involvement. Of note, the terms cicatricial pemphigoid and mucous membrane pemphigoid are synonymous and are used interchangeably throughout this report.

Case Presentation

Our patient is a 71-year-old man with a history of CP affecting his left eye and trachea who presented to the emergency department with progressively worsening dyspnea.

The patient has a history of multiple bronchoscopies; the most recent one showed tracheal pemphigoid lesions partially obstructing his airway. His diagnosis of cicatricial pemphigoid had been made over fifteen years prior to the current presentation via biopsy and subsequent immunofluorescence staining. On admission, his respiratory rate was 21 breaths/min and his oxygen saturation was 97% on 50% Bipap: 14/8. He was admitted to the intensive care unit for evaluation and management of his acute hypoxic respiratory failure.

Initially, a fiberoptic bronchoscopy was performed under laryngeal mask airway (LMA) general anesthesia. Dense, dark-colored lesions were noted to be occluding most of the trachea, consistent with the patient’s history of tracheal CP (Figure 1).

Figure 1. Patient’s trachea demonstrating heavy burden of cicatricial pemphigoid lesions prior to any intervention

They were partially removed in a piecemeal manner with forceps instrumentation. After this procedure, the patient still required supplemental oxygen, oscillating between BiPAP and nasal cannula. Two days later, he was started on rituximab, which he had also received during previous relapses.

On hospital day four, our cardiothoracic surgery team performed bronchoscopy with laser ablation under LMA general anesthesia. After the procedure, the patient’s tracheal lesions had markedly decreased in size (Figure 2).

Figure 2. Patient’s trachea with reduced lesions status-post bronchoscopy with laser ablation.

He was also entirely weaned off supplemental oxygen.

In the following weeks, the patient’s symptom burden was significantly decreased. He reported an improvement in his quality of life and satisfaction with the procedure. A subsequent repeat laser ablation was planned at the three-month mark. This procedure was more technically challenging due to airway-narrowing caused by an increase in scar tissue from the initial laser ablation. Due to the risks imposed by the interval changes in the patient’s anatomy, we decided against further laser therapy. In the absence of laser treatments, the patient’s tracheal pemphigoid recurred and symptoms returned to their prior state. He currently receives interval fiberoptic bronchoscopies to partially remove his lesions when they threaten his airway.

Discussion 

In a study involving subjects with aggressive ocular CP, 81% of patients achieved clinical remission with rituximab therapy (4). Medical therapy had repeatedly failed to reduce our patient’s symptoms, making his case unique in both its rarity and refractory nature. With no other options, our team developed an innovative treatment modality in an attempt to offer our patient some symptomatic relief.

Previous case reports have shown the utility of low-level laser therapy in mucous membranous lesions (5-7). One study showed successful resection of an obstructive mass caused by CP and restoration of airway patency using a Holmium LASER (2100nm) (8-9). We decided to ablate/resect the inflammatory tissue using an Nd:YAG LASER (1064nm) given its medium penetration length (1-4mm), coagulopathic ability (high heme absorption), and decreased tissue destruction when compared to the Ho:YAG laser; which has a higher laser absorption coefficient with water.

To our knowledge, this is the first case report of successful treatment of cicatricial pemphigoid with Nd:YAG laser (1064nm) ablation therapy. This procedure resulted in immediate, although ultimately impermanent, improvement in our patient’s respiratory insufficiency. Our patient also reported an improved quality of life during the period of time the laser ablation therapy offered him symptomatic relief. He was able to attend his grandchildren’s’ soccer games and walk to the end of his driveway to get his newspaper, activities he had not be able to participate in for years.

While our patient’s improvement was temporary, his disease process was uniquely advanced. It is possible that patients with less advanced disease may experience longer periods of remission with laser-mediated therapy, or may be able to tolerate repeated laser ablation procedures. Importantly, our patient’s case demonstrates that laser therapy can significantly reduce the burden of pemphigoid lesions, and can lead to a better quality of life for a disease process with few alternative treatment modalities.

Conclusion 

Therapeutic fiberoptic bronchoscopy with laser ablation is a promising treatment for patients suffering from CP of the trachea. Future investigations should focus on optimizing the laser ablation technique to achieve safe and sustained results.

References

1. Fleming TE, Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol. 2000 Oct;43(4):571-91. [CrossRef] [PubMed]
2. Minaie A, Surani SR. Mucous Membrane Pemphigoid with Tracheal Involvement. Case Rep Pulmonol. 2016;2016:5749784. [CrossRef] [PubMed]
3. Kato K, Moriyama Y, Saito H, Koga H, Hashimoto T. A case of mucous membrane pemphigoid involving the trachea and bronchus with autoantibodies to β3 subunit of laminin-332. Acta Derm Venereol. 2014 Mar;94(2):237-8. [CrossRef] [PubMed]
4. You C, Lamba N, Lasave AF, Ma L, Diaz MH, Foster CS. Rituximab in the treatment of ocular cicatricial pemphigoid: a retrospective cohort study. Graefes Arch Clin Exp Ophthalmol. 2017 Jun;255(6):1221-1228. [CrossRef] [PubMed]
5. Oliveira PC, Reis Junior JA, Lacerda JA, Silveira NT, Santos JM, Vitale MC, Pinheiro AL. Laser light may improve the symptoms of oral lesions of cicatricial pemphigoid: a case report. Photomed Laser Surg. 2009 Oct;27(5):825-8. [CrossRef] [PubMed]
6. Yilmaz HG, Kusakci-Seker B, Bayindir H, Tözüm TF. Low-level laser therapy in the treatment of mucous membrane pemphigoid: a promising procedure. J Periodontol. 2010 Aug;81(8):1226-30. [CrossRef] [PubMed]
7. Minicucci EM, Miot HA, Barraviera SR, Almeida-Lopes L. Low-level laser therapy on the treatment of oral and cutaneous pemphigus vulgaris: case report. Lasers Med Sci. 2012 Sep;27(5):1103-6. [CrossRef] [PubMed]
8. Jalil BA, Abdou YG, Rosen SA, Dammad T. Mucous Membrane Pemphigoid Causing Central Airway Obstruction. J Bronchology Interv Pulmonol. 2017 Oct;24(4):334-338. [CrossRef] [PubMed]
9. Benge E, Yamaguchi L, Tran V, Sheikhan N, Bhatia S, Mcwhorter Y, Collier J, Chung A. Successful Treatment of Cicatricial Pemphigoid of the Trachea with Laser Ablation Bronchoscopy. Chest. 2021 Oct 1;160(4):A1999-2000 [Abstract]. [CrossRef]

Abbreviations

• Bipap: bilevel positive airway pressure
• CP: cicatricial pemphigoid
• Ho:YAG: holmium-doped yttrium aluminum garnet
• Laser: light amplification by stimulated emission of radiation
• LMA: laryngeal mask airway
• Nd:YAG: neodymium-doped yttrium aluminum garnet

Disclosures

Conflicts of Interest: The above listed authors have no conflicts of interest to declare.
Funding: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.
This case was presented at the CHEST Annual Meeting that took place from Oct 17, 2021 – Oct 20, 2021 in a virtual format.

Cite as: Benge E, Tran V, Sheikhan N, Bhatia S, McWhorter Y, Collier J, Chung A. Symptomatic Improvement in Cicatricial Pemphigoid of the Trachea Achieved with Laser Ablation Bronchoscopy. Southwest J Pulm Crit Care. 2022;24(1):8-11. doi: https://doi.org/10.13175/swjpcc058-21 PDF 

A Summary of Outpatient Recommendations for COVID-19 Patients and Providers December 9, 2021

Richard A. Robbins MD¹

Stephen A. Klotz MD²

¹Phoenix Pulmonary and Critical Care Research and Education Foundation, Gilbert, AZ USA

²Division of Infectious Disease, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ USA

We thought a follow-up to our original brief review of COVID-19 in February, 2020 might be useful. As we write this in early December 2021, we again caution that this area is rapidly changing and what is true today will likely be outdated tomorrow. We again borrowed heavily from the Centers for Disease Control (CDC)  CDC website and the NIH website which have extensive discussions over numerous pages covering COVID-19. Our hope is to condense those recommendations. We do not discuss inpatient care in any detail.

COVID-19 Variants

The initial steps of coronavirus infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptors which are normally on a cell. These include human aminopeptidase N (APN; HCoV-229E), angiotensin-converting enzyme 2 (ACE2; HCoV-NL63, SARS-CoV and SARS-CoV-2) and dipeptidyl peptidase 4 (DPP4; MERS-CoV).

All viruses, but especially simple single-stranded RNA viruses like COVID-19, constantly change through mutation resulting in new variants (1). The variants vary in severity and infectivity. The CDC, World Health Organization (WHO), and other public health organizations monitor COVID-19 for emergence of new variants. Some variants emerge and disappear while others persist.

The Delta variant causes more infections and spreads faster than the original SARS-CoV-2 strain of the virus that cause COVID-19 (2). Delta is currently the predominant variant of the virus in the United States causing over 99% of infections (2). On November 24, 2021, a new variant of SARS-CoV-2, B.1.1.529, was reported to the World Health Organization (WHO). This new variant was first detected in specimens collected on November 11, 2021 in Botswana and on November 14, 2021 in South Africa. On November 26, 2021, WHO named the B.1.1.529 Omicron and classified it as a variant of concern because of the number of mutations on the spike protein. As of this yesterday morning (12/8/21), the first Omicron case was reported in Arizona (2). Omicron is also present in California, Utah and Colorado and probably several other states since there is a lag between the presence of the virus and detection.

Early reports have suggested the Omicron variant might cause milder disease more often in children, raising hopes that the variant might be less severe than some of its predecessors (3). Dr. Müge Çevik, an infectious-disease specialist at the University of St Andrews, UK cautions, “Everyone is trying to find some data that could guide us but it’s very difficult at the moment.”

Symptoms

People with COVID-19 have had a wide range of symptoms reported – from none to severe illness (2). Symptoms may appear 2-14 days after exposure to the virus. Symptoms of flu and COVID-19 may be very similar and it may be hard to tell the difference between them based on symptoms alone. Testing may be needed to help confirm a diagnosis. COVID-19 seems to spread more easily than flu and causes more serious illnesses in some people. It can also take longer before people show symptoms and people can be contagious for longer. Despite mild symptoms, people infected with COVID-19 can still infect others.

Testing

Two types of viral tests are used: nucleic acid amplification tests and antigen tests (2). A viral test checks specimens from the nose or mouth by first reverse transcribing the RNA to DNA and then amplifying the DNA by polymerase chain reaction. COVID-19 antigen tests are designed for the rapid diagnosis of active infection primarily by detecting the nucleocapsid protein antigen of the SARS-CoV-2 virus. People who develop symptoms or have come into close contact with someone with COVID-19 should be tested 5–7 days after their last exposure or immediately if symptoms develop.

Prevention

The CDC recommends several steps for prevention of COVID-19 (2).

1. Get Vaccinated. COVID-19 vaccines are protective against COVID-19, especially severe disease and death. Boosters should be administered as soon as possible.
2. Wear a mask. Everyone 2 years or older who is not fully vaccinated should wear a mask in indoor public places. In general, masks are unnecessary in outdoor settings.
3. However, in areas with high numbers of COVID-19 cases, consideration should be given to wearing a mask in crowded outdoor settings and for activities with close contact with others who are not fully vaccinated.
4. Stay 6 feet away from others. Whenever possible, people should stay 6 feet away from others especially those who are sick. If possible, patients should be advised to maintain 6 feet between sick family members.
5. Avoid crowds and poorly ventilated spaces. Crowded places like restaurants, bars, fitness centers, or movie theaters are high risk areas for spread of COVID-19. Indoor spaces that do not offer fresh air from the outdoors should be avoided.
6. Test to prevent spread to others. Testing provides information about the risk of spreading COVID-19. Over-the-counter self-tests can be used at home or anywhere, are easy to use, and produce rapid results.
7. Wash Hands Often. Hands should be washed often with soap and water after the patient blows their nose, coughs, sneezes, or is exposed to any public place.
8. Clean and disinfect. High touch surfaces should be cleaned and disinfected regularly or as needed. This includes tables, doorknobs, light switches, countertops, handles, desks, phones, keyboards, toilets, faucets, and sinks.

Specific Groups

Any immunocompromised group or group living in close contact is at increased risk for COVID-19 infection and complications of the infection (2). This includes asthma, pregnancy, the elderly (>65 years), nearly all chronic diseases and jails or prisons.

Holidays

With Holiday gatherings here, many are concerned about COVID-19 especially with an unvaccinated relative or guest. First, the CDC recommends they get vaccinated (2). Second follow the recommendations under prevention above.

COVID-19 Patients

Patients with COVID-19, should follow the steps under prevention above (2). In addition, they stay home for 10 days after symptoms appear except to get medical care. Patients should be advised to drink fluids, take over-the-counter medications for symptomatic relief, and go to the emergency room or a physician’s office if needed, but call ahead. They should tell their close contacts that they may have been exposed to COVID-19.

COVID-19 Exposure

Patients should quarantine if you have been in close contact (within 6 feet of someone for a cumulative total of 15 minutes or more over a 24-hour period) with someone who has COVID-19, unless they are fully vaccinated (2). People who are fully vaccinated do not need to quarantine after contact with someone who had COVID-19 unless they have symptoms.

Travel

At this time patients should delay travel by bus, train, plane or ship unless fully vaccinated.

Treatment

The NIH has convened a COVID-19 Treatment Guidelines Panel (4). They recommend*:

1. COVID-19 vaccination for everyone who is eligible according to the Advisory Committee on Immunization Practices (AI).
2. Using one of the following anti-SARS-CoV-2 monoclonal antibodies (as post-exposure prophylaxis (PEP) for people who are at high risk of progressing to severe COVID-19:
   • Bamlanivimab 700 mg plus etesevimab 1,400 mg administered as an intravenous (IV) infusion (BIII).
   • Casirivimab 600 mg plus imdevimab 600 mg administered as subcutaneous injections (AI) or an IV infusion (BIII).
3. Do not use hydroxychloroquine for SARS-CoV-2 PEP (AI).
4. Do not use of other drugs for SARS-CoV-2 PEP, except in a clinical trial (AIII).
5. Do not use any drugs for SARS-CoV-2 pre-exposure prophylaxis, except in a clinical trial (AIII).

*Rating of Recommendations: A = Strong; B = Moderate; C = Optional Rating of Evidence: I = One or more randomized trials without major limitations; IIa = Other randomized trials or subgroup analyses of randomized trials; IIb = Nonrandomized trials or observational cohort studies; III = Expert opinion

References

1. Yang H, Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat Rev Microbiol. 2021 Nov;19(11):685-700. [CrossRef] [PubMed]
2. CDC. COVID-19. Available at: https://www.cdc.gov/coronavirus/2019-ncov/index.html (accessed 12-6-21).
3. Callaway E, Ledford H. How bad is Omicron? What scientists know so far. Nature. 2021 Dec 2. [CrossRef] [PubMed]
4. NIH. COVID-19 Treatment Guidelines. October 27, 2021. Available at: https://www.covid19treatmentguidelines.nih.gov/ (accessed 12/6/21).

Cite as: Robbins RA, Klotz SA. A Summary of Outpatient Recommendations for COVID-19 Patients and Providers December 9, 2021. Southwest J Pulm Crit Care. 2021;23(6):151-5. doi: https://doi.org/10.13175/swjpcc066-21 PDF 

Alveolopleural Fistula In COVID-19 Treated with Bronchoscopic Occlusion with a Swan-Ganz Catheter

Nathaniel Hitt DO¹

Aleksey Tagintsev DO¹

Douglas Summerfield MD¹

Evan Schmitz MD² 

¹MercyOne North Iowa Medical Center, Des Moines, IA USA

²Airod Medical, Gainesville, FL USA

Abstract

Pneumothorax and pneumomediastinum are known complications of COVID-19 patients. They have been documented to occur both with and without mechanical ventilation. There are several reports of cases further complicated by alveolopleural or bronchopleural fistulas. However, there are no studies and only a few case reports on the treatment options used for alveolopleural fistulas in COVID-19 patients. To our knowledge, there is only one report of bronchoscopic treatment with endobronchial valves in a COVID-19 patient. We present the case of a 63-year-old male with COVID-19, pneumothorax, and an alveolopleural fistula that was successfully sealed using bronchoscopic occlusion with a Swan-Ganz catheter.

Abbreviation List

• COVID-19: Severe acute respiratory distress syndrome coronavirus-2
• PAL: Persistent air leak
• APF: Alveolopleural fistula
• PaO2: Partial pressure of arterial oxygen
• FiO2: Fraction of inspired oxygen

Background

Pneumothorax complicates 1% of COVID-19 hospital admissions and the risk increases with mechanical ventilation (1). There have been several reports of pneumothoraces in COVID-19 complicated by persistent air leaks (PAL) and alveolopleural fistulas (APFs) (1-3). APFs are a communication between the pulmonary parenchyma of the alveoli and the pleural cavity. The most common cause is lung reduction surgery, but it can also be present following spontaneous pneumothorax.  Less commonly it can be caused by pulmonary infection. Clinically, APFs present as a PAL on chest tube drainage with a PAL defined as a duration greater than 5 days. Complications include pleural infection and ventilation/perfusion mismatch with a loss of positive end expiratory pressure.  APFs in non-COVID patients have been associated with an increased duration of chest tube, prolonged hospital stay, and increased morbidity a drainage and mortality. Treatments in non-COVID patients have ranged from insertion of additional thoracostomy tubes, surgical intervention, and bronchoscopic intervention (2). There is one reported case of an APF in COVID-19 successfully treated with endobronchial valves (3). Here we present the case of an APF in COVID-19 treated with bronchoscopic occlusion with a Swan-Ganz catheter.

Case Presentation

The patient was a 63-year-old man diagnosed with COVID-19 who required intubation, mechanical ventilation, and admission to the critical care unit. On hospital day 2 chest x-ray revealed bilateral pneumothoraces requiring chest tube placement. Bilateral PAL was present and on hospital day 10 the patient developed a moderate sized right sided pneumothorax despite the adequately positioned chest tube. The initial thoracostomy tube was replaced with a large bore chest tube with immediate resolution of the pneumothorax. However, a moderate air leak persisted and by hospital day 14, the diagnosis of APF was suspected. Bronchoscopic occlusion using the balloon of a Swan-Ganz catheter was performed.

A Swan-Ganz catheter was inserted through the endotracheal tube and along-side of a bronchoscope. The balloon was sequentially inflated and deflated to occlude each lobe to assess for air leak resolution. The air leak was reduced, but not resolved with occlusion of the right lower lobe and right middle lobe individually. The balloon was inflated just enough to occlude the right bronchus intermedius with near complete resolution of the leak (Figure 1).

Figure 1. Chest radiograph showing Swan-Ganz catheter (yellow arrow) with its cuff inflated in the right bronchus intermedius to seal an alveolopleural fistula.

The patient was observed for ten minutes to ensure tolerability before concluding the procedure. He was kept paralyzed to reduce coughing. After 3 days the air leak resolved, the Swan-Ganz catheter was removed, and the air leak remained sealed. The PaO2:FiO2 ratio improved from 79 to 250. However, despite initial improvement and no air leak the patient's conditioned worsened in the setting of multisystem organ failure. Multisystem organ failure was attributed to a combination of severe acute respiratory distress syndrome, cytokine storm, and septic shock from a urinary tract infection. The patient's family made the decision to withdraw care on day 22.

Discussion

Despite several cases of refractory pneumothorax in COVID-19, the significance and optimal treatment remains unclear (1,3,4). There is one report of two COVID-19 patients treated with thoracoscopy, bleb resection, and pleurectomy(4) and a single report of endobronchial valves (3). Conservative management with prolonged chest tube remains the recommended treatment (2). The American College of Chest Physicians guidelines only recommend bronchoscopic treatment in refractory cases when surgery is not possible (2). This patient was not a surgical candidate due to his instability, endobronchial valves were unavailable at our facility, and at height of the COVID-19 pandemic, transfer to a tertiary care center was not possible. Bronchoscopic occlusion with a balloon catheter has been described previously in a case a of PAL secondary to polymicrobial pneumonia, pulmonary interstitial emphysema, and in a case of necrotic lung complicated by hydropneumothorax (2,5,6). Bronchoscopy in COVID-19 is associated with an increased risk of infection and its use should be limited if possible. In this case, it was determined that with proper personal protective equipment and lack of access to other treatments, bronchoscopic occlusion was the best option.

An 8.0 French Swan-Ganz catheter was selected for its balloon that connects to an integrated stopcock to maintain inflation and for its relative availability. We classified the PAL as an APF after the leak was revealed to be distal to the segmental bronchi. The average time to resolution is reported to be 4-7.5 days (2). The decision to maintain occlusion for 3 days was based on the above average, patient improvement, and the lack of drainage from the occluded lung. The risk of infection, in particular pneumonia and empyema, must be considered when using this technique.  Ideally, an endobronchial valve would have been available to allow a one-way valve to drain secretions (2). Our patient was closely monitored for developing pulmonary infection with daily chest radiography and, following the removal of the Swan-Ganz Catheter, a bacterial sputum culture which was negative.

Conclusion

There are no randomized controlled trials investigating which treatment of PALs is most effective or safe in COVID-19 patients or even in non-COVID-19 patients (2). Furthermore, pneumothorax and persistent air leaks in COVID-19 patients have not been universally shown to increase mortality (1). However, considering the known morbidity and mortality associated with PALs, we suggest it may be reasonable in cases refractory to thoracostomy tube to treat with a Swan-Ganz catheter when otherresources are not available.

Acknowledgement

Peter L. Larsen PhD for editorial and administrative support.

References

1. Martinelli AW, Ingle T, Newman J, et al. COVID-19 and pneumothorax: a multicentre retrospective case series. Eur Respir J. 2020 Nov 19;56(5):2002697. [CrossRef] [PubMed]
2. Sakata KK, Reisenauer JS, Kern RM, Mullon JJ. Persistent air leak - review. Respir Med. 2018 Apr;137:213-218. [CrossRef] [PubMed]
3. Pathak V, Waite J, Chalise SN. Use of endobronchial valve to treat COVID-19 adult respiratory distress syndrome-related alveolopleural fistula. Lung India. 2021 Mar;38(Supplement):S69-S71. [CrossRef] [PubMed]
4. Aiolfi A, Biraghi T, Montisci A, et al. Management of Persistent Pneumothorax With Thoracoscopy and Bleb Resection in COVID-19 Patients. Ann Thorac Surg. 2020 Nov;110(5):e413-e415. [CrossRef] [PubMed]
5. Ellis JH, Sequeira FW, Weber TR, Eigen H, Fitzgerald JF. Balloon catheter occlusion of bronchopleural fistulae. AJR Am J Roentgenol. 1982 Jan;138(1):157-9. [CrossRef] [PubMed]
6. Schmitz ED. A new interventional bronchoscopy technique for the treatment of bronchopleural fistula. Southwest J Pulm Crit Care. 2017;15(4):174-8. [CrossRef]

Cite as: Hitt N, Tagintsev A, Summerfield D, Schmitz E. Alveolopleural Fistula In COVID-19 Treated with Bronchoscopic Occlusion with a Swan-Ganz Catheter. Southwest J Pulm Crit Care. 2021;23(4):100-3. doi: https://doi.org/10.13175/swjpcc026-21 PDF 

Repeat Episodes of Massive Hemoptysis Due to an Anomalous Origin of the Right Bronchial Artery in a Patient with a History of Coccidioidomycosis

Blerina Asllanaj, MD

Elizabeth Benge MD

Yi McWhworter DO

Sapna Bhatia MD

Department of Internal Medicine

HCA Healthcare

Mountain View Hospital

Las Vegas, NV, USA

Abstract

Anomalous bronchial arteries originate outside the space bound by the T5 and T6 vertebrae at the major bronchi. Here, we highlight a case of a 37-year-old man with a past medical history of coccidioidomycosis and who presented with massive hemoptysis. A bronchial angiogram showed the patient had a right bronchial artery originating anomalously from the left subclavian artery. The patient ultimately underwent a bronchial artery embolization, after which he achieved symptomatic remission.

Introduction

Hemoptysis from primary coccioidomycosis is unusual and should prompt a search for other causes (1). These could include bronchitis, malignancy, or rarely, a fungus ball. Anomalous bronchial arteries have origins outside the space bound by the T5 and T6 vertebrae at the level of the major bronchi (2). Bronchial artery embolization is the standard treatment for patients with ruptured anomalous bronchial arteries and resultant hemoptysis (3). Here, we present a unique case of a 37-year-old male with a past medical history of coccidioidomycosis and previous episodes of massive hemoptysis who was found to have an anomalous right bronchial artery originating in his left subclavian artery. Symptomatic remission was achieved with bronchial artery embolization. To our knowledge, this is the only reported case of a patient with a history coccidioidomycosis and a ruptured anomalous right bronchial artery that was successfully treated with bronchial artery embolization.

Case Presentation

Our patient is a 37-year-old man with a past medical history significant for coccidioidomycosis (resolved nine years prior) and previous episodes of massive hemoptysis who presented to our emergency room with multiple episodes of hemoptysis over the course of one day. On admission, he reported a five-pack year smoking history. He denied hematemesis, dyspnea, and angina, a history venous thromboembolism and alcohol and recreational drug use.

In the emergency department, the patient was afebrile, his blood pressure was 177/119 mmHg, heart rate was 96 beats/min, respiratory rate was 16 breaths/minute, and his oxygen saturation was 95% on room air. The patient’s physical exam revealed diffuse rales throughout the right lung and decreased breath sounds in the right lower lobe. The remainder of the patient’s physical exam was negative for acute abnormalities.

His lab values on admission were significant only for an elevated D-dimer at 1.28 mcg/mL; his hemoglobin was 14.2 gm/dL and his INR was 0.93 sec/mL. His chest radiograph showed ill-defined patchy parenchymal densities over the bilateral lower lobes (Figure 1).

Figure 1. Chest x-ray reveals ill-defined patchy parenchymal densities over the lower lobes suggest evolving multifocal pneumonia or atypical viral pneumonia.

He experienced a witnessed episode of hemoptysis, expectorating 300 cc’s of blood, prompting an emergent bronchoscopy. During the bronchoscopy, bloody secretions were noted to in his right lower lobe. A five centimeter dark red gelatinous material was removed and sent for pathology studies alongside bronchoalveolar lavage washings. Two mL’s of 2% epinephrine were administered, after which no active oozing was noted. The patient was then intubated for airway protection and admitted to the intensive care unit.   

A repeat chest radiograph revealed opacification throughout the right lung with evidence of volume loss (Figure 2).

Figure 2. Chest x-ray showing interval development of opacification throughout the right lung with evidence of volume loss including rightward mediastinal shift. The left lung is clear.

The patient was empirically treated for atypical pneumonia with azithromycin, ceftriaxone, dexamethasone, and albuterol breathing treatments. A computed tomography angiogram (CTA) of the chest with contrast showed multifocal flocculent and nodular infiltrate posterolateral aspect right lower lobe as well as mild mucous plugging and bronchial edema. Bronchial angiography confirmed the branching of the right bronchial artery from the left subclavian artery (Figure 3) and evidence of shunting to the right lower lobe (Figure 4).

Figure 3. Bronchial angiography prior to embolization- right bronchial artery directly arising from the left subclavian artery and is unusually large in caliber.

Figure 4. Bronchial angiography confirms opacification of the right lower lobe.

After the aberrant artery was confirmed on bronchial angiogram, the patient underwent a right bronchial artery embolization. He was subsequently extubated. Pathology and bronchoalveolar lavage studies revealed blood; the patient’s infectious and autoimmune work-up were entirely negative. He was discharged home with self-care. To date, the patient has only experienced one episode of hemoptysis status-post embolization.

Discussion

Differential diagnoses for massive hemoptysis include pulmonary infections, such as coccidioidomycosis, invasive aspergillosis and Mycobacterium tuberculosis, and cardiovascular causes, including anomalous origin of bronchial arteries. A thorough diagnostic evaluation is needed to identify the causative underlying pathology, site of bleeding, and vascular anatomy, so that the appropriate treatment can be initiated (3).

Common origins of the bronchial arteries include the inferior aortic arch, distal descending thoracic aorta, subclavian artery, brachiocephalic trunk, thyrocervical trunk and coronary artery (5). A bronchial angiogram was pivotal in the evaluation of the anatomy of the bronchial arteries in our patient’s case, as it allowed for the optimal artery embolization due to the identification of an anomalous artery early in his treatment course.

The bronchial arteries can become dilated and tortuous due to chronic inflammatory diseases such as bronchiectasis, coccidioidomycosis and tuberculosis, and are prone to vascular remodeling; rendering them fragile (6). The new collateral vessels have thin walls, making them prone to rupture and bleeding. In our patient’s case, chronic inflammation related to his prior coccidioidomycosis infection contributed to the remodeling of his anomalous right bronchial artery, rendering it prone to rupture and therefore the likely culprit of his massive hemoptysis.

Conclusion

Overall, this case emphasizes the importance of recognizing the fragility of anomalous bronchial arteries. A history of previous episodes of hemoptysis can alert clinicians to the possibility of a congenital abnormality exacerbated by subsequent infection.   

References

1. Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis. 2016 Sep 15;63(6):e112-46. [CrossRef] [PubMed]
2. Battal, B., Saglam M, Ors F et al. Aberrant right bronchial artery originating from right coronary artery–MDCT angiography findings. Br J Radiol. 2010;83(989): e101–e104. [CrossRef] [PubMed]
3. Keller FS, Rosch J, Loflin TG, Nath PH, McElvein RB. Nonbronchial systemic collateral arteries: significance in percutaneous embolotherapy for hemoptysis. Radiology. 1987 Sep;164(3):687-92. [CrossRef] [PubMed]
4. Ittrich H, Bockhorn M, Klose H, Simon M. The Diagnosis and Treatment of Hemoptysis. Dtsch Arztebl Int. 2017 Jun 5;114(21):371-381. [CrossRef] [PubMed]
5. Hartmann IJ, Remy-Jardin M, Menchini L, Teisseire A, Khalil C, Remy J. Ectopic origin of bronchial arteries: assessment with multidetector helical CT angiography. Eur Radiol. 2007 Aug;17(8):1943-53. [CrossRef] [PubMed]
6. Kathuria H, Hollingsworth HM, Vilvendhan R, Reardon C. Management of life-threatening hemoptysis. J Intensive Care. 2020 Apr 5;8:23. [CrossRef] [PubMed]

Cite as: Asllanaj B, Benge E, McWhworter Y, Bhatia S. Repeat Episodes of Massive Hemoptysis Due to an Anomalous Origin of the Right Bronchial Artery in a Patient with a History of Coccidioidomycosis. Southwest J Pulm Crit Care. 2021;23(3):89-92. doi: https://doi.org/10.13175/swjpcc037-21 PDF 

June 2021 Pulmonary Case of the Month: More Than a Frog in the Throat

Michael B. Gotway, MD

Department of Radiology, Mayo Clinic Arizona

Phoenix, Arizona 85054

A 66-year-old woman with a history of GERD and previous renal transplant due to lithium toxicity was seen in the clinic complaining of a shortness of breath and nonproductive cough. She was on immunosuppression due to her renal transplant done about 5 months ago. These include daily trimethoprim (TMP) – sulfamethoxazole (SMX). She also had asthma and was on a long-acting bronchodilator with an inhaled corticosteroid. Because of a previous history of oropharyngeal candidiasis (thrush), she was doing nystatin swish and swallow four times a day.

Which of the following should be included in your differential diagnosis in this clinical setting? (Click on the correct answer to be directed to the second of 5 pages. Multiple guesses are allowed.)

1. Candida esophagitis
2. COVID-19 Infection
3. Cytomegalovirus esophagitis
4. Group A Streptococcus infection
5. All of the above

Cite as: Gotway MB. June 2021 Pulmonary Case of the Month: More Than a Frog in the Throat. Southwest J Pulm Crit Care. 2021;22(6):109-13. doi: https://doi.org/10.13175/swjpcc017-21 PDF 

Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis

Babulal Bansiwal¹

Maneesha Jelia²

Ramesh Chand Meena²

Satyam Agarwal²

Shinu A²

Departments of ¹Respiratory Medicine and ²Anatomy

Government Medical College, Kota

Rajasthan 324010, India

Abstract

Background: Tuberculosis (TB) can infect both pulmonary and extra-pulmonary organs. In India pulmonary TB accounts for 80% of cases and extrapulmonary TB (EPTB) accounts for 20% cases. Cervical lymph nodes are the most location for EPTB.

Aims and Objectives: To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Methods: A total of 60 patients were enrolled in the study all with EPTB and cervical lymphadenitis. These 60 study patients were randomised into two groups. Group-I consisted of 30 patients given anti-tuberculosis therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5 mg/kg body weight over 4 weeks. Group-II was comprised of 30 patients given antituberculosis treatment plus placebo

Results: After completion of treatment 27 patients in Group 1 (90%) showed complete resolution and 3 patients (10%) had residual evidence of lymphadenitis with no change. In contrast, only 19 patients (63.3%) showed complete resolution in Group 2 and 11 patients (36.7%) had residual lymphadenitis present (10 had no change, 1 had increase in size).

Conclusion: We conclude that steroids given with antituberculosis treatment to patients with cervical lymphadenitis led to faster and earlier resolution of tuberculous lymphadenitis.

Introduction

Tuberculosis (TB) is an ancient disease that affects both pulmonary and extra-pulmonary organs. In India most TB cases are pulmonary (80%) but extrapulmonary TB (EPTB) accounts for a substantial proportion (20%) (1). Peripheral lymph node tuberculosis is observed in about 5% of all TB patients and 30-55% of extra-pulmonary TB cases (2). Cervical lymph nodes are the most common lymph nodes affected, classically termed as “scrofula”, although supraclavicular, axillary, inguinal nodes may also be involved (3-5). Lymphadenopathy may lead to complications by compression of adjacent structures, organs, and blood vessels or fistula formation (6-10). Multiple studies have shown better outcomes with addition of steroids to anti-tuberculosis treatment in extrapulmonary tuberculosis including pleural effusion, pericardial effusion, tubercular meningitis, and mediastinal lymphadenopathy (11,12). However, the safety and efficacy of this approach remains largely unproven except in cases of intrathoracic obstruction where it was found to relieve the pressure on the compressed bronchus (13).

Aims and Objectives

To study the efficacy of treatment with oral steroids along with anti-tuberculosis treatment in cervical lymph node tuberculosis.

Materials and Methods

Patients: Sixty patients with cervical lymph node tuberculosis seen from 1st October 2013 to 30^th September 2014 in the Department of Respiratory Medicine, Government Medical College, Kota, India participated in the study. All cases of cervical lymph node tuberculosis found to have cyto-pathological, histo-pathological, immunological and/or bacteriological evidence of TB and who had not received any anti- tuberculosis therapy in the past, were included in the study. Patients were excluded if they were pregnant or had a chronic disease such as diabetes mellitus, hypertension, peptic ulcer disease, alcoholism, or HIV-AIDS. Patients were also excluded if they had a detectable abscess.

Study Design: The study was an open label, randomized, prospective and placebo-controlled interventional study comparing the efficacy of the addition of two months treatment with oral corticosteroids along with Revised National Tuberculosis Control Programme (RNTCP) recommended anti-TB therapy.

Sixty patients were randomised into two groups by a computer-generated random table. All patients were given category I anti-tuberculosis therapy (ATT) consisting of INH 600 mg and rifampicin 450 mg daily for 6 months with pyrazinamide 1500 mg daily for the first 2 months. Group-I consisted of 30 patients given category I RNTCP-recommended therapy along with prednisolone 1mg/kg body weight for 4 weeks followed by tapering at 0.5mg/kg body weight for 4 weeks. Group-II was comprised of 30 patients given category I RNTCP-recommended therapy plus placebo.

All the study cases were monitored clinically by visits after 1, 2 and 6 months.

Statistical Analysis: Pearson’s x² test or Fisher’s exact test was used to evaluate correlations between categorical variables, as appropriate. Relationships among continuous variables was evaluated using Student’s t- test. All tests of significance are two-tailed, and p < 0.05 was considered to reflect significance.

Results

The patients were well matched between groups in age (27.5 + 12.9 years vs. 26.3 + 11.7 years, p=0.612) and sex (12M/18F vs. 11M/19F). The groups were well-matched in other clinical characteristics (Table 1).

Table 1. Clinical characteristics of patients at beginning of therapy.

In addition to the above, the patients were well-matched by the extent of both upper and lower lymphadenopathy (Group I, 25/30; Group 2, 28/30), absence of chest lesions (Group I, 1/30; Group 2, 2/30), and positive histopathology on needle aspiration (Group I, 27/30; Group 2, 26/30). Out of 26 patients of Group II, 4 (13.3%) patients were diagnosed by AFB smear of the needle aspirate as well as cytopathological examination, 2(6.7%) had only AFB smear positivity and 22 (86.7%) had only cytopathological confirmation. None had a positive sputum smear.

Most of the patients in Group-I had earlier lymph node resolution compared to Group-II (Table 2).

Table 2. Initial lymph node status and after varying durations of treatment.

This table shows the status of the lymph node initially and after varying duration of treatment. After completion of treatment 27 patients (90%) showed complete resolution and only 3 patients (10%) had no change in Group-I. In contrast, only 19 patients (63.3%) in Group-II showed complete resolution and 11 patients (36.7%) had residual lymph nodes (10 with no change, 1 with an increase in size). Most patients had a negative AFB smear from the needle aspirate after 6 months in both Group-I (27 patients) and group-II (26 patients).

Only 2 patients in Group-I (6.67%) had complications as compared to 09 (30.0%) in Group-II (p<0.001). The complications were in the form of abscess, sinus and/or new lymph node/s. All these patients needed surgical exploration during the course of treatment. Sequelae in form of residual lymph node was also higher in Group II patients (10 out of 30 patients) as compared to Group I (3 out of 30, p<0.001).

Overall, the incidence of side effects was greater in Group-II. This difference was mostly due to a higher occurrence of joints pain and skin rashes in Group-II than Group-I, (8 and 4 patients vs. 1 and 1 patients respectively).

Discussion

The present study was done to determine the role of steroids in the management of cervical lymph node tuberculosis. In contrast to 20 patients (66.67%) in the non-steroid group-II who had complete resolution after 6 months, 27 patients (90%) in the steroid group had complete resolution. Blaikely et al. (14) reported complete resolution in 82% of their non-steroid study patients which was similar to results of our study.

In the present clinical study, only 2 patients (6.66%) in the steroid group had complications as compared to 9 (30.0%) in the non-steroid group. The complications were in the form of abscess, sinus and/or new lymph node/s. In Group II, fresh lymph nodes appeared in 4, existing lymph node increased in 1, abscess formation occurred in 3 while 2 patients developed sinuses. Sequela in the form of residual lymph node was also higher in the non-steroid patients (10 out of 30, 33.33%) as compared to the steroid treated patients (3 out of 30 patients, 5%, p<0.001). Results were comparable to other studies (15).

We used a moderate dose of steroids for 2 months. The major concern against the use of steroids when given along with anti-TB treatment in tubercular lymphadenitis are adverse systemic effects. However, the overall incidence of side effects with anti-TB treatment were more in the non-steroid group in the form of joint pains and skin rashes, (8 and 4 patients v/s 1 and 1 patients respectively). Gastro-intestinal side effects i.e. nausea/vomiting and pain abdomen, were slightly higher in the steroid-treated patients.

Conclusion

We conclude that steroids when given along with anti-tubercular treatment led to faster and earlier resolution of tuberculous lymphadenitis. Complication and sequela in form of residual lymph node are also less in steroid group as compared to non-steroid group. It is unclear if long-term outcomes are affected. However, this data suggests that justification for routine use of corticosteroids could be made in tubercular cervical lymphadenitis.

References

1. Arora V, Jaiswal AK, Gupta S, Gupta MB, Jain V, Ghanchi F. Implementation of RNTCP in a private medical college: five years' experience. Indian J Tuberc. 2012 Jul;59(3):145-50. [PubMed].
2. Asghar RJ, Pratt RH, Kammerer JS, Navin TR. Tuberculosis in South Asians living in the United States, 1993-2004. Arch Intern Med. 2008 May 12;168(9):936-42. [CrossRef] [PubMed]
3. Lazarus AA, Thilagar B. Tuberculous lymphadenitis. Dis Mon. 2007 Jan;53(1):10-5. [CrossRef]  [PubMed]Thompson MM, Underwood MJ, Sayers RD, Dookeran KA, Bell PR. Peripheral tuberculous lymphadenopathy: a review of 67 cases. Br J Surg. 1992 Aug;79(8):763-4. [CrossRef] [PubMed]
4. Dandapat MC, Mishra BM, Dash SP, Kar PK. Peripheral lymph node tuberculosis: a review of 80 cases. Br J Surg. 1990 Aug;77(8):911-2. [CrossRef] [PubMed]
5. Singh B, Moodley M, Goga AD, Haffejee AA. Dysphagia secondary to tuberculous lymphadenitis. S Afr J Surg. 1996 Nov;34(4):197-9. [PubMed]
6. Gupta SP, Arora A, Bhargava DK. An unusual presentation of oesophageal tuberculosis. Tuber Lung Dis. 1992 Jun;73(3):174-6. [CrossRef] [PubMed]
7. Ohtake M, Saito H, Okuno M, Yamamoto S, Ohgimi T. Esophagomediastinal fistula as a complication of tuberculous mediastinal lymphadenitis. Intern Med. 1996 Dec;35(12):984-6. [CrossRef] [PubMed]
8. Wilson RS, White RJ. Lymph node tuberculosis presenting as chyluria. Thorax. 1976 Oct;31(5):617-20. [CrossRef] [PubMed]
9. Puri S, Khurana SB, Malhotra S. Tuberculous abdominal lymphadenopathy causing reversible renovascular hypertension. J Assoc Physicians India. 2000 May;48(5):530-2. [PubMed]
10. Mansour AA, Al-Rbeay TB. Adjunct therapy with corticosteroids or paracentesis for treatment of tuberculous pleural effusion. East Mediterr Health J. 2006 Sep;12(5):504-8. [PubMed]
11. Reuter H, Burgess LJ, Louw VJ, Doubell AF. The management of tuberculous pericardial effusion: experience in 233 consecutive patients. Cardiovasc J S Afr. 2007 Jan-Feb;18(1):20-5. [PubMed]
12. Nemir RL, Cardona J, Vaziri F, Toledo R. Prednisone as an adjunct in the chemotherapy of lymph node-bronchial tuberculosis in childhood: a double-blind study. II. Further term observation. Am Rev Respir Dis. 1967 Mar;95(3):402-10. [CrossRef] [PubMed]
13. Jha BC, Dass A, Nagarkar NM, Gupta R, Singhal S. Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in management. Postgrad Med J. 2001 Mar;77(905):185-7. [CrossRef] [PubMed]
14. Blaikley JF, Khalid S, Ormerod LP. Management of peripheral lymph node tuberculosis in routine practice: an unselected 10-year cohort. Int J Tuberc Lung Dis. 2011 Mar;15(3):375-8. [PubMed]
15.  Allen MB, Cooke NJ. Corticosteroids and tuberculosis. BMJ. 1991 Oct 12;303(6807):871-2. [CrossRef] [PubMed]

Cite as: Bansiwal B, Jelia M, Chand Meena RC, Agarwal S, A S. Adjunctive Effects of Oral Steroids Along with Anti-Tuberculosis Drugs in the Management of Cervical Lymph Node Tuberculosis. Southwest J Pulm Crit Care. 2021;22(1):16-20. doi: https://doi.org/10.13175/swjpcc067-20 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

September 2020 Pulmonary Case of the Month: An Apeeling Example

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 67-year-old woman who developed a chronic nonproductive cough beginning in October 2019. After 4 weeks, she consulted her primary care physician.

PMH, SH, and FH

• She had a history of several prior pneumonias, including respiratory syncytial virus in 2018
• Irritable bowel syndrome
• Hypertension
• Prior smoker: 28 pack years, none since 1999
• FH negative

Physical Examination

Her physical examination is recorded as unremarkable other than decreased nasal flow.

Which of the following is/are common cause(s) of a chronic cough? (Click on the correct answer to be directed to the second of seven pages)

1. Cough-variant asthma
2. Gastroesophageal reflux disease
3. Upper airway cough syndrome (UACS) secondary to rhinosinus diseases
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2020 pulmonary case of the month: an apeeling example. Southwest J Pulm Crit Care. 2020;21(3):56-63. doi: https://doi.org/10.13175/swjpcc048-20 PDF

June 2020 Pulmonary Case of the Month: Twist and Shout

Lewis J. Wesselius, MD¹

Staci E. Beamer, MD² 

¹Departments of Pulmonary Medicine and ²Thoracic Surgery

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 83-year-old man presented with a left upper lobe lung nodule. The nodule was noted on a routine follow-up chest radiograph obtained after a radical cystectomy and left nephro-ureterectomy done 9 months earlier for invasive bladder cancer as well clear cell carcinoma of left kidney. He had symptoms of a mild chronic cough but denied shortness of breath with activities of daily living.

PMH, SH, FH

• Prostate cancer, post prostatectomy in 2009. 
• Bladder cancer and left renal cell cancer resected in Jan 2019
• Post-op chemotherapy after bladder and left kidney resections
• Non-ischemic cardiomyopathy, possibly due to            chemotherapy, EF 45%
• Chronic atrial fibrillation
• Smoking history: 60 pack years, no occupational exposures

Physical Examination

Other than an irregular pulse, his physical examination was unremarkable.

Medications

• Warfarin
• Atorvastatin
• Hydrochlorothiazide
• Ramipril
• Atenolol

Radiography

The initial chest radiograph is shown in Figure 1.

Figure 1. Initial chest x-ray.

Which of the following should be done at this time? (Click on the correct answer to be directed to the second of eight pages)

1. Chest CT scan
2. Left upper lobectomy
3. Comparison to old chest x-rays
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ, Beamer SE. June 2020 pulmonary case of the month: twist and shout. Southwest J Pulm Crit Care. 2020;20(6):179-87. doi: https://doi.org/10.13175/swjpcc038-20 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]
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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 

Brief Review of Coronavirus for Healthcare Professionals February 10, 2020

Richard A. Robbins, MD¹

Stephen A. Klotz, MD²

¹Phoenix Pulmonary and Critical Care Research and Education Foundation, Gilbert, AZ USA

²Division of Infectious Diseases, Department of Internal Medicine, University of Arizona, Tucson, AZ USA

The epidemic of coronavirus (2019-nCoV) near Wuhan City and the surrounding Hubei Province in China has received extensive news coverage. Some have predicted the virus will cause a worldwide pandemic (1). The CDC has an extensive website discussing over numerous pages whom to suspect, how to diagnose and how to treat 2019-nCoV. 2019-nCoV represents the most recent of the severe coronaviral infections. Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are also caused by coronaviruses that have jumped from animals to humans like 2019-nCoV. It should be remembered that there are only 12 confirmed cases of 2019-nCoV in the US and the mortality rate appears to be only about 3% which is lower than SARS or MERS (2,3). This could be offset by a greater infectiousness of 2019-nCoV resulting in more aggregate infectious, and hence, deaths.

Anyone with a fever who has recently visited the epidemic area in China or been exposed to someone with known 2019-nCoV should be quarantined (2). The only reliable symptom has been fever (98%) (4). Cough (76%), myalgia/fatigue (44%), sputum production (28%), headache (8%), hemoptysis (5%), and diarrhea (3%) were much less common. The clinical course was characterized by the development of dyspnea in 55% of patients and lymphopenia in 66%.

Persons suspected of 2019-nCoV should be quarantined and reported to their local state health departments. The incubation period appears about 2-14 days and is spread by person-to-person transmission based on the previous MERS epidemic (2). There is no need to wear masks in the US where the incidence is low and they are likely ineffective (2).

Diagnosis is made real-time reverse transcription polymerase chain reaction (rRT-PCR) assay. This was only available from the CDC but very recently the CDC has made kits available to state health departments (2).

At present the treatment for 2019-nCoV is supportive in appropriate respiratory isolation to protect healthcare workers. A randomized, controlled trial of Gilead’s antiviral drug remdesivir used to treat Ebola is currently underway in China in hopes that it will be an effective treatment for 2019-nCoV (5).

Please be aware that this information is current as of February 10, 2020. It is likely to change.

References

1. McNeil DG Jr. Wuhan coronavirus looks increasingly like a pandemic, experts say. New York Times. February 2, 2020. Available at: https://www.nytimes.com/2020/02/02/health/coronavirus-pandemic-china.html (accessed 2/10/20).
2. Centers for Disease Control. 2019 Novel Coronavirus (2019-nCoV) in the U.S. February 10, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html (accessed 2/10/20).
3. Worldometer. Novel coronavirus (2019-nCoV) mortality rate. Available at: https://www.worldometers.info/coronavirus/coronavirus-death-rate/ (accessed 2/10/20).
4. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Jan 24. pii: S0140-6736(20)30183-5. [Epub ahead of print] [CrossRef] [PubMed]
5. Wetsman N. An experimental antiviral medication might help fight the new coronavirus. The Verge. Feb 4, 2020. Available at: https://www.theverge.com/2020/2/4/21122327/coronavirus-experimental-medication-treatment-wuhan-china-gilead-hiv (accessed 2/10/20).

Cite as: Robbins RA, Klotz SA. Brief review of coronavirus for healthcare professionals February 10, 2020. Southwest J Pulm Crit Care. 2020;20(2):69-70. doi: https://doi.org/10.13175/swjpcc011-20 PDF