Broncholithiasis has a low incidence rate. Herein, we report partial atelectasis in the right middle lobe in a patient with asthma symptoms. Fiberoptic bronchoscopy revealed broncholithiasis colonized filamentous fungi. The patient’s asthma symptoms immediately improved after removing the bronchial stone. Hence, filamentous fungi were partly associated with the symptoms. To the best of our knowledge, this is the first case report of asthma exacerbation caused by filamentous fungi-related broncholithiasis.
Case Report
An 81-year-old Japanese male patient was diagnosed with and treated for asthma at another hospital. He received budesonide/formoterol inhalation at a dose of 640/18 μg/day. He visited our hospital on June 28, 2019, due to a persistent cough and wheezing. The patient had no history of smoking or contact with animals and soil.
The physical examination results were unremarkable except for minimal wheezing on the chest with forced exhalation. Fever was not observed. The laboratory tests showed that the patient’s peripheral white blood count was normal. However, the eosinophil (483 μg/mL) and total serum immunoglobulin E levels (1938 IU/ml) were high. Further, the radioallergosorbent test, which is used to examine the amount of immunoglobulin E antibodies against nine aeroallergens, had positive results.
Chest computed tomography (CT) scan revealed partial atelectasis in the right middle lobe [Figure 1]. An allergic reaction to the fungus was suspected. Curschmann’s spiral and Charcot–Leyden crystal were detected on the sputum smear. The patient’s pulmonary function was normal (forced expiratory volume in the first second [FEV1]: 1.91 L, FEV1% [FEV1/forced vital capacity]: 74.0%).
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Figure 1: Chest computed tomography findings. (a) Arrow showed partial atelectasis in the right middle lobe, (b) after stone removal, the right middle lobe bronchus opened
Fiberoptic bronchoscopy under local anesthesia was performed to investigate the cause of atelectasis. A white stone with a diameter of approximately 1 cm was found in the right middle lobe bronchus. After confirming its mobility, it was removed [Figure 2]. Histologically, the stone was calcified with filamentous fungi with septa [Figure 3]. Ceriporia lacerata was detected on the sputum culture repeatedly. Therefore, bronchial colonization of filamentous fungi was considered. Persistent cough and wheezing disappeared after removing the bronchial stone. In addition, atelectasis improved immediately after removal without relapse.
Figure 2: Fiberoptic bronchoscopy findings. (a) White stone with a diameter of approximately 1 cm was found in the right middle lobe bronchus, (b) right middle lobe bronchus after removal of the stone
Figure 3: Pathological findings. Pathologically, the stone was calcified with filamentous fungi and septa. (a) H and E, ×400, (b) Grocott methenamine silver staining, ×100
Discussion
Broncholithiasis is defined as the presence of calcified or ossified materials within the tracheobronchial tree.[1] Broncholithiasis is a rare disease. Hence, its incidence and prevalence are unknown. The causes of broncholithiasis include calcification of bronchial secretions and inhalation of foreign substances, calcification of bronchial cartilage, migration of calcified components, and perforation of calcified lymph nodes into the bronchi.[2] Necrotizing granulomatous mediastinal lymphadenitis attributed to tuberculosis and histoplasmosis are the most common causes of broncholithiasis. Moreover, other infections are associated with the pathogenesis of broncholithiasis. Cryptococcosis, Coccidioidomycosis,[3] Endobronchial Aspergillosis,[4] Endobronchial Nocardiosis, and disseminated Mycobacterium kansasii[5] can also cause broncholithiasis.
Stone formation caused by the retention of bronchial secretion may be observed in bronchiectasis and pulmonary aspergillosis. However, there are no reports on filamentous fungi involvement as in this case. Ceriporia lacerate is a wood-inhabiting white-rot fungus and is ubiquitous in the environment. It was first isolated in 1994 from decayed wood in Miyawaki forest in Japan.[6] C. lacerate produces white to buff dense nonsporulating colonies. The fungus has been associated with a wide spectrum of clinical manifestations ranging from saprobic colonization to fungal pneumonia.[7] Filamentous fungi can colonize the respiratory tracts of patients with underlying conditions, including chronic sinusitis, chronic obstructive pulmonary diseases, interstitial lung disease, posttubercular sequelae, and asthma. However, C. lacerate containing filamentous fungi can colonize the respiratory tract of individuals with anatomical lung damage or seemingly normal lungs. Although colonization is not recognized in most instances and it may be discovered incidentally,[4] respiratory symptoms can be attributed to colonization in some cases.
The most common symptoms of broncholithiasis are prolonged cough (45%–100%) and hemoptysis (26%–75%).[8] Wheezing can develop if there is partial bronchial obstruction. Wheezing caused by broncholithiasis is often localized. In this case, it was also observed these symptoms, and the patient was treated for bronchial asthma.
Filamentous fungi are found in the environment and are involved in the exacerbation of asthma. Severe asthma with fungal sensitization (SAFS) is defined as severe asthma with evident fungal colonization or airway sensitization.[9] According to the diagnostic criteria of SAFS, allergic bronchopulmonary aspergillosis was ruled out in this case, and there was no previous history of oral corticosteroid treatment for severe asthma. Further, immediate skin reaction or serum-specific immunoglobulin G antibody positivity to the causative fungus is challenging to confirm. In this case, the patient presented with eosinophilia. The filamentous fungi caused eosinophilic ETosis, which leads to viscous ETosis, allergic airway inflammation, and bronchial asthma symptoms. The patient did not meet the diagnostic criteria of SAFS. However, broncholithiasis could have caused mucous membrane damage attributed to filamentous fungi colonization, resulting in airway inflammation.
Broncholithiasis have multiple management options, which include assessment, endoscopic removal, and surgery. However, there are no established treatment guidelines. In this case, persistent cough and atelectasis with calcification in the right middle lobe on CT scan were observed. Thus, bronchoscopy was essential. The use of bronchoscopy for both diagnosis and concurrent removal of mucus plugs would prevent local inflammation at the early stages.[10] Bronchoscopy revealed stones in the right middle lobe bronchus. Next, stone removal through bronchoscopy was performed. After the procedure, atelectasis and airway symptoms improved. Therefore, stone removal through bronchoscopy was effective in improving clinical symptoms.
Herein, we present a rare case of filamentous fungi-related broncholithiasis associated with asthma exacerbation.
Author contributors
- C. N. wrote the manuscript
- O. T. provided pathology findings and helped to write the manuscript
- H. M. is a supervisor and edited the manuscript
- K. N. is a co-supervisor and edited the manuscript
- All authors reviewed and approved the final manuscript.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
We would like to thank Dr. Katsuhiko Kamei, Medical Mycology Research Center, Chiba University.
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