Bronchial stent implantation in patient with bronchial obstruction caused by pulmonary mucormycosis: a case report

Introduction

Mucormycosis is an acute suppurative disease caused by any fungus in the order Mucorales, primarily affecting immunocompromised patients. Clinically, mucormycosis can be classified into several types based on the site of infection, including pulmonary, rhinocerebral, cutaneous, gastrointestinal, and disseminated forms (1). This report presents a patient diagnosed with pulmonary mucormycosis (PM) complicated by bronchial obstruction, who was deemed ineligible for surgery. We therefore had to compromise and palliate his bronchial obstruction with a bronchial stent while continuing intravenous, nebulized, and bronchoscopically applied antifungals. However, despite these measures, the aggressive underlying infection continued to progress, ultimately leading to erosion into a major vessel and catastrophic hemoptysis. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-277/rc).

Case presentation

A 39-year-old male patient with uncontrolled diabetes mellitus had experienced recurrent episodes of diabetic ketoacidosis. The patient experienced recurrent fever and persistent chest tightness for one month. Despite undergoing antibiotics therapy at other hospitals, the symptoms continued to persist. Multiple scans of computed tomography (CT) showed a progressive enlargement and worsening of the infection site. The pre-admission CT scans showed an enlarged right hilar region, truncation of the right middle lobe bronchus accompanied by associated atelectasis, and inflammation in the right lower lobe (Figure 1). For further diagnosis and treatment, the patient was admitted to our hospital on April 21st, 2023.

Figure 1 Chest CT scans of pulmonary mucormycosis on April 18th: the bronchus of the right middle lobe of the lung exhibited truncation with associated atelectasis, and inflammation was observed in the right lower lobe. CT, computed tomography.

Physical examination revealed diminished breath sounds in the right lower lung field, accompanied by bilateral moist rales; no pleural friction rub was observed. Laboratory tests showed a white blood cell count of 5.38×10⁹/L, hemoglobin level of 98 g/L, platelet count of 344×10⁹/L, and C-reactive protein of 20.57 mg/L. Urinalysis showed negative ketones but positive for glucose (4+). D-dimer levels were measured at 1.50 µg/mL, fasting blood glucose was recorded at 30.30 mmol/L, and both galactomannan and 1,3-beta-D-glucan tests returned negative results. The patient underwent a comprehensive bronchoscopy upon admission to the hospital. The examination showed a large amount of yellow secretions in multiple bronchi of the right lung, with the surface of the right intermediate bronchus and the right middle lobe bronchus extensively covered by a white pseudomembrane. Histopathological examination of the biopsy from the right middle lobe tissue showed extensive necrotic regions containing structures morphologically consistent with fungal hyphae, indicative of a Mucorales infection. Special staining results were positive for Periodic acid-Schiff (PAS), negative for acid-fast, and positive for hexamine silver (Figure 2A-2C). The next-generation sequencing (NGS) analysis of the bronchoalveolar lavage fluid identified Rhizopus oryzae, a species belonging to the Mucorales order. The patient was administered intravenous liposomal amphotericin B upon admission to the hospital and subsequently initiated aerosol inhalation of liposomal amphotericin B two days later. However, the therapeutic response was unsatisfactory. Consequently, on May 10th, the patient’s treatment regimen was revised to include intravenous isavuconazole. The CT scans performed 2 days after the treatment change showed further enlargement of the right hilar region, the presence of bilateral pleural effusions, partial atelectasis of lung tissue, and a marked progression of the condition compared to the previous examination (Figure 3). During hospitalization, the patient underwent multiple fiberoptic bronchoscopy procedures, including sputum aspiration, irrigation to remove purulent secretions, and localized administration of liposomal amphotericin B. Fiberoptic bronchoscopy performed on average weekly showed an extensive white pseudomembrane covering the surface of the right intermediate bronchus and the right middle lobe bronchus, as well as a large amount of yellow secretions. Over time, the lumen of the right intermediate bronchus progressively transitioned from stenosis to complete occlusion (Figure 4A-4D). During hospitalization, the patient experienced a significant intensification of chest tightness, along with recurrent fever, with body temperature ranging from 38 to 39 ℃. Bronchoscopy showed a large amount of purulent secretions, indicating that the fever was likely due to insufficient drainage of the pus. The evaluation by the thoracic surgery department revealed a critical obstruction of the right intermediate bronchus, and the CT scans showed that the lesion not only involved the pulmonary arteries but also had disseminated to the mediastinum. The patient’s lesion exhibited a tendency to spread to the left side, indicating that a simple total right pneumonectomy would be inadequate to resolve the issue comprehensively, and the surgical risks were considered high. Additionally, the patient’s poorly controlled blood glucose levels could result in poor postoperative wound healing. Ultimately, the patient was evaluated and deemed inoperable due to the extensive burden of mediastinal invasion and the significant risk of contralateral spread of infection. We conducted a comprehensive discussion with the patient’s family members, highlighting the patient’s poor response to antifungal therapy and the persistent necrosis of the lesion, all of which increased the risk of sepsis and septic shock throughout the disease progression. Furthermore, given the invasive nature of mucormycosis affecting blood vessels, the risk of massive hemoptysis in the future cannot be ruled out. The family members clearly demonstrated their understanding of the situation and strongly requested more aggressive treatment. After a comprehensive evaluation of the patient’s condition, we decided to perform bronchial stent implantation via bronchoscopy to improve ventilation function and effectively facilitate the drainage of purulent secretions. The patient underwent bronchoscopy under general anesthesia on May 31st. Under the endoscopy, it was observed that the opening of the right intermediate bronchus was obstructed by white necrotic material. The tracheal mucosa demonstrated marked hypertrophy accompanied by granulation tissue hyperplasia, rendering it susceptible to hemorrhage upon contact, and direct visualization of the distal bronchus was unattainable. Subsequently, based on the patient’s height of 175 cm and weight of 70 kg, we implanted a bare self-expanding metal stent of 12 mm × 30 mm. After the bronchial stent implantation, it was observed that the opening of the basal segment of the lower lobe remained unobstructed, and a large amount of purulent secretions flowed out (Figure 4E). The subsequent bronchoscopy performed three days later showed that the stent within the right middle bronchus remained correctly positioned and patent (Figure 4F).

Figure 2 Histopathological examination of the right middle lobe tissue biopsy: (A) H&E staining at 400×; (B) hexamine silver staining at 400×; (C) PAS staining at 400×. Extensive necrotic regions containing structures morphologically consistent with fungal hyphae, indicative of a Mucorales infection. Special staining results were positive for PAS, negative for acid-fast, and positive for hexamine silver. H&E, hematoxylin and eosin; PAS, Periodic acid-Schiff.

Figure 3 Chest CT scans of pulmonary mucormycosis on May 12th: bilateral pleural effusion and partial atelectasis of lung tissue were noted, indicating progression from the previous scans. CT, computed tomography.

Figure 4 The observation results of the bronchoscopy examination. (A) On April 23rd, a large amount of white pseudomembrane was visible covering the right intermediate bronchus. (B) On April 28th, the opening of the right intermediate bronchus became narrowed. (C) On May 6th, the right intermediate bronchus was narrowed and accompanied by granuloma formation. (D) On May 16th, the right intermediate bronchus was completely occluded and the endoscope could not pass through. (E) On May 31st, a metal tracheal stent was placed in the right intermediate bronchus. (F) On June 2nd, the tracheal stent in the right intermediate bronchus was in the normal position and unobstructed.

After the bronchial stent implantation and purulent fluid drainage surgery, the patient’s body temperature improved. The re-examination CT scans on June 8th showed an enlarged right hilar region, obstructive atelectasis of the right middle lobe bronchus, bilateral pleural effusion, and partial incomplete expansion of the right lung tissue (Figure 5). The CT examination showed that the patient’s condition had improved, however, the volume of pleural effusion had increased compared to previous findings. Consequently, a closed thoracic drainage procedure was performed. The patient suffered from bronchial obstruction due to intense inflammatory reaction. It was recommended to remove the stent once the bronchus had been restored to patency. However, this procedure carried a significant risk of massive hemoptysis. At present, the patient’s family members opted to defer the removal of the bronchial stent. On June 12th, the patient experienced sudden massive hemoptysis, with a substantial volume of blood emanating from the nose and mouth. The patient rapidly lost consciousness and became unresponsive to external stimuli. In response to this emergency, tracheal intubation and mechanical ventilation were promptly initiated, alongside cardiopulmonary resuscitation (CPR). Despite these interventions, the patient could not be revived and unfortunately succumbed to their condition.

Figure 5 Chest CT scans of pulmonary mucormycosis on June 8th: obstructive atelectasis in the right middle lobe of the lung persisted, along with ongoing bilateral pleural effusion and partial atelectasis of the right lung tissue. CT, computed tomography.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Discussion

PM is a severe, acute suppurative lung infection caused by fungi belonging to the Mucorales order, predominantly affecting patients with compromised immune function and comorbidities (1). Key risk factors for this condition encompass hematological or solid organ malignancies, hematopoietic stem cell or solid organ transplantation, prolonged use of corticosteroids or immunosuppressive agents, diabetes (with or without ketoacidosis), among others (2). The incidence of mucormycosis has shown a rising trend annually, with higher rates observed in developing countries compared to developed nations (3,4). PM typically manifests as an acute or subacute condition, characterized by symptoms such as coughing, fever, and potentially chest tightness, dyspnea, chest pain, and hemoptysis. The hyphae associated with this disease can infiltrate blood vessels, leading to thrombosis and tissue necrosis. In severe instances, this can result in massive hemoptysis, posing a significant threat to the patient’s life. Furthermore, the hyphae may invade the trachea and bronchi, leading to airway obstruction. Additionally, the infection may spread to adjacent structures such as the mediastinum, pericardium, and chest wall (5). The imaging manifestations of PM lack specificity. Early CT examinations may reveal exudation and peripheral ground-glass opacities, which can subsequently progress to consolidation and nodular lesions. These lesions are primarily located in the upper lobes of the lungs and may be accompanied by cavitation, pleural effusion, and mediastinal lymphadenopathy (6,7). The definitive diagnosis of PM relies on histopathological examination of tissue specimens. Mucor species exhibit right-angle branching under microscopy, characterized by broad, non-septate or sparsely septate hyphae with irregular thickness. High-throughput sequencing technology can function as a complementary method for pathogen identification (8,9). PM exhibits resistance to many antifungal agents. Currently, the primary effective anti-mucormycosis drugs include liposomal amphotericin B, posaconazole, and isavuconazole, etc. (10,11). First-line treatment strongly recommends intravenous infusion of liposomal amphotericin B, isavuconazole, or posaconazole (or oral posaconazole sustained-release tablets). For cases where liposomal amphotericin B treatment fails, posaconazole or isavuconazole are also strongly recommended as salvage therapies (12,13). For patients with PM who are in stable general condition and whose lesions are localized to a single lung lobe, surgical resection of the affected lung tissue is widely recommended. Combining surgical intervention with antifungal therapy can significantly improve patient outcomes (14). For patients who are deemed unsuitable for surgery, local drug therapy, such as aerosol inhalation or bronchoscopic localized administration of liposomal amphotericin B, may provide therapeutic benefits. However, the availability of high-quality evidence supporting this approach is currently limited (15).

Tracheal stents can partially alleviate dyspnea in patients with severe airway stenosis and are utilized to maintain airway patency following dilation of post-inflammatory and infectious stenosis. The indications and outcomes of using various types of tracheal stents for treating benign airway stenosis have garnered increasing attention (16-18). Currently, the most widely used tracheal stents in clinical procedures are silicone and metallic stents. Silicone stents necessitate rigid bronchoscopy for implantation, whereas metal stents can be deployed via flexible bronchoscopy (19). The advancements in flexible bronchoscopy technology have significantly contributed to the increased utilization of metal stents over silicone stents. Commonly used metal stents include uncovered, partially covered and fully covered stents (20). Fully covered metal stents have been employed in clinical practice for benign diseases, while partially covered or uncovered metal stents are generally avoided due to concerns about excessive granulation tissue formation and potential erosion into surrounding structures, including blood vessels. In contrast, bare-metal stents offer advantages such as lower cost, easier repositioning or removal if further treatment or adjustment is needed, and better adaptation to the natural curvature and movement of the trachea (17). In this case, our patient presented with a high burden of invasive disease and was deemed ineligible for surgery. We therefore had to compromise and palliate his bronchial obstruction with a bronchial stent while continuing intravenous, nebulized, and bronchoscopically applied antifungals. The intervention markedly alleviated the patient’s symptoms of chest tightness and dyspnea. However, despite these measures, the aggressive underlying infection continued to progress, ultimately leading to erosion into a major vessel and catastrophic hemoptysis. Although it has not been definitively proven that the bronchial stent increased the risk of hemoptysis, this possibility cannot be ruled out. On one hand, the bronchial stent is unable to completely eradicate the lesion compared to surgical resection, thereby failing to eliminate the risk of hemoptysis caused by mucormycosis invading blood vessels. On the other hand, the bronchial stent has shown a positive impact in alleviating the patient’s symptoms. Consequently, in similar cases, a cautious approach should be adopted when considering bronchial stent implantation, and the rationality and necessity of such interventions require further evaluation. Where feasible, it is advisable to prioritize the use of covered stents for temporary implantation to minimize the risk of local granulation tissue formation. And the stent should be removed at the earliest appropriate opportunity to minimize the risk of stent embedding into the airway wall or adhesion to surrounding tissues.

Conclusions

The clinical and imaging manifestations of PM are non-specific. Consequently, early recognition and accurate diagnosis are critical for effective management, particularly in immunocompromised individuals and diabetic patients with uncontrolled blood glucose levels. Prompt diagnosis and timely intervention are essential to optimize outcomes. Appropriate surgical resection of the affected tissue can markedly enhance patient prognosis (21,22). However, the potential benefits of bronchial stents in patients unsuitable for surgery require further investigation.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-277/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-277/prf

Funding: This research was supported by Suzhou Science and Technology Development Plan (No. SKY2023162) and Suzhou University Horizontal Project (Nos. P112208521 and P112201223).

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-277/coif). Both authors report that this research was supported by Suzhou Science and Technology Development Plan (No. SKY2023162) and Suzhou University Horizontal Project (Nos. P112208521 and P112201223). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Reid G, Lynch JP 3rd, Fishbein MC, et al. Mucormycosis. Semin Respir Crit Care Med 2020;41:99-114. [Crossref] [PubMed]
2. Alqarihi A, Kontoyiannis DP, Ibrahim AS. Mucormycosis in 2023: an update on pathogenesis and management. Front Cell Infect Microbiol 2023;13:1254919. [Crossref] [PubMed]
3. Danion F, Coste A, Le Hyaric C, et al. What Is New in Pulmonary Mucormycosis? J Fungi (Basel) 2023;9:307. [Crossref] [PubMed]
4. Prakash H, Chakrabarti A. Global Epidemiology of Mucormycosis. J Fungi (Basel) 2019;5:26. [Crossref] [PubMed]
5. Petrikkos G, Skiada A, Lortholary O, et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012;54:S23-34. [Crossref] [PubMed]
6. Agrawal R, Yeldandi A, Savas H, et al. Pulmonary Mucormycosis: Risk Factors, Radiologic Findings, and Pathologic Correlation. Radiographics 2020;40:656-66. [Crossref] [PubMed]
7. Jung J, Kim MY, Lee HJ, et al. Comparison of computed tomographic findings in pulmonary mucormycosis and invasive pulmonary aspergillosis. Clin Microbiol Infect 2015;21:684.e11-8. [Crossref] [PubMed]
8. Skiada A, Lass-Floerl C, Klimko N, et al. Challenges in the diagnosis and treatment of mucormycosis. Med Mycol 2018;56:93-101. [Crossref] [PubMed]
9. Lin E, Moua T, Limper AH. Pulmonary mucormycosis: clinical features and outcomes. Infection 2017;45:443-8. [Crossref] [PubMed]
10. Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017;102:433-44. [Crossref] [PubMed]
11. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019;19:e405-21. [Crossref] [PubMed]
12. Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis 2016;16:828-37. [Crossref] [PubMed]
13. Allen D, Wilson D, Drew R, et al. Azole antifungals: 35 years of invasive fungal infection management. Expert Rev Anti Infect Ther 2015;13:787-98. [Crossref] [PubMed]
14. Afolayan O, Copeland H, Hargrove R, et al. Successful Treatment of Invasive Pulmonary Mucormycosis in an Immunocompromised Patient. Ann Thorac Surg 2016;101:e117-9. [Crossref] [PubMed]
15. Zeng P, Mu XD, Wang LJ, et al. Bronchoscopic manifestations and interventional treatment of pulmonary mucormycosis. Zhonghua Jie He He Hu Xi Za Zhi 2023;46:151-7. [PubMed]
16. Zou H, Zhang J, Zhan K, et al. A narrative review of new research progress regarding the use of airway stents in benign airway stenosis. Expert Rev Respir Med 2022;16:651-9. [Crossref] [PubMed]
17. Li L, Zhang X, Shi J, et al. Airway Stents from Now to the Future: A Narrative Review. Respiration 2023;102:439-48. [Crossref] [PubMed]
18. Fortin M, Lacasse Y, Elharrar X, et al. Safety and Efficacy of a Fully Covered Self-Expandable Metallic Stent in Benign Airway Stenosis. Respiration 2017;93:430-5. [Crossref] [PubMed]
19. Saito Y, Imamura H. Airway stenting. Surg Today 2005;35:265-70. [Crossref] [PubMed]
20. Ayub A, Al-Ayoubi AM, Bhora FY. Stents for airway strictures: selection and results. J Thorac Dis 2017;9:S116-21. [Crossref] [PubMed]
21. Lynch JP 3rd, Fishbein MC, Abtin F, et al. Part 1: Mucormycosis: prevalence, risk factors, clinical features, and diagnosis. Expert Rev Anti Infect Ther 2023;21:723-36. [Crossref] [PubMed]
22. Lynch JP 3rd, Zhanel GG. Part 2: mucormycosis: focus on therapy. Expert Rev Anti Infect Ther 2023;21:737-48. [Crossref] [PubMed]