Nontuberculous mycobacterial (NTM) diseases are common infectious diseases in the United States, and the number of NTM isolates has recently exceeded that of Mycobacterium tuberculosis isolates.1,2 Skin tests have shown that the frequency of NTM sensitization in the United States has been increasing.3 In Japan, the number of NTM patients has increased 25-fold over the last 25 years.4 More than 125 species of NTM have been identified; however, Mycobacterium avium and Mycobacterium intracellulare (both referred to as M. avium complex: MAC) are the most common NTM pathogens.5 Patients with MAC infections often show thin-walled cavities on computed tomography (CT),6,7 but there have been few reports of bronchoscopic examination of the inner walls of the cavities caused by MAC. Here, we report a case of MAC pulmonary infection with cavitation in which the cavitary lumen was directly visualized through flexible bronchoscopy during the course of treatment.
A 58-year-old man was admitted to Toranomon Hospital because of fever and loss of appetite. Fourteen years earlier, he had undergone a radical middle to lower esophagectomy and proximal gastrectomy with reconstruction of the gastric conduit for treatment of esophageal cancer. Routine chest radiography and high-resolution CT 12 years after the surgery revealed multiple small cavitary lesions in the right upper lobe (Figs. 1A, 2A). He was diagnosed as having M. avium infection by bronchial lavage culture; however, the cavities could not be observed through bronchoscopy at that time. He was treated with daily rifampicin 450 mg/d, ethambutol 750 mg/d, and clarithromycin 600 mg/d. Two months after treatment, he discontinued rifampicin and ethambutol because of loss of appetite but continued with clarithromycin 400 mg/d monotherapy at another clinic. After 2 years of treatment with clarithromycin, he developed fever and loss of appetite for 2 weeks and revisited our hospital. The complete blood count was normal. His serum C-reactive protein level was 2.8 mg/dL, and his fasting glucose and hemoglobin A1C levels were both normal. His antibodies were negative for human immunodeficiency, hepatitis B, and hepatitis C viruses. Chest radiography revealed a dense infiltrate around the cavities in the right upper and middle lung fields, with a shift of the mediastinum to the right. New infiltrations were seen in the left apex (Fig. 1B). High-resolution CT revealed enlarged thick-walled cavities, with destruction of partitions and lung parenchyma in the right upper lobe. Consolidations, small well-defined nodules, and bronchiectasis were also observed in the right lower and left upper lobes (Fig. 2B).
Bronchoscopic examination was performed using a 4.9-mm bronchoscope (LTF TYPE 260; Olympus, Tokyo, Japan). A large cavity was directly visible through both the posterior and the anterior segmental bronchi of the right upper lobe (Fig. 3A). The inner wall was almost completely covered with thick gray debris (Fig. 3B). Microscopy of biopsy specimens of the debris showed necrotic tissue, and a culture of the cavitary lavage was found to be positive for M. avium. The organism was found to be clarithromycin resistant.
The patient was treated with streptomycin 0.75 g 3 times a week and daily rifabutin 300 mg/d, levofloxacin 500 mg/d, and ethambutol 500 mg/d. Six months later, chest radiography showed improvement of the consolidated opacities around the cavities (Fig. 1C). High-resolution CT also showed decreased cavitary wall thickening and consolidation (Fig. 2C). Bronchoscopic examination demonstrated decrease in the gray debris of the inner wall (Fig. 3C). A culture of the cavitary lavage was negative. Three months after the last bronchoscopic examination, Aspergillus fumigatus was detected in the patient’s sputum culture. He was administered micafungin 150 mg/d; however, he suffered sudden death because of massive hemoptysis. An autopsy was performed.
The cavitary walls of the right lung consisted of collapsed lung parenchyma or fibrous tissue, and their inner surface were covered with either hemorrhages or granulation tissue along with aggregates of fungal hyphae (Fig. 4). A culture of the lung tissue obtained at autopsy was positive for A. fumigatus but not M. avium.
We used high-resolution CT and flexible bronchoscopy to successfully observe serial changes in the inner walls of the cavities in a patient with M. avium pulmonary infection. The thin-walled cavities have often been observed by CT in NTM patients.6–8 Christensen et al9 reported that 88% NTM patients had cavities; however, the size of these cavities was relatively smaller and was ranged between 2 and 4 cm in nearly half of these patients. To our knowledge, visualization of cavities by bronchoscopy has been reported in only 3 NTM patients, and all of these reports were published in the Japanese literature.10,11 Niijima and Edo11 reported pulmonary cavities observed through an ultra-thin bronchoscope in 15 patients who had lung cancer, aspergillosis, tuberculosis, or NTM infections. They divided the cavities into 2 groups on the basis of their appearance: the red cavity group (n=5) and the necrotic cavity group (n=10). The necrotic cavity group tended to have longer clinical courses compared with those of the red cavity group. Our patient had a cavitary M. avium infection for approximately 2 years, and his cavities can be categorized as necrotic.
The cavities are predictors of poor response to treatment and have an important role in MAC infection.12 The mechanisms of cavity formation in MAC patients are not clear. Two hypotheses have been proposed: (1) a check-valve mechanism and (2) the discharge of the necrotic tissue containing MAC to the draining bronchus.13,14 Fujita et al14 reported the pathologic analysis of 9 patients with MAC infection. MAC existed predominantly in the caseating necrotic tissue of the inner walls of the cavities and not in the bronchus. In the patient in the present study, we could not find any bronchial stenosis or obstruction in the right upper lobe, suggesting that cavity formation was caused by a discharge of necrotic tissue to the draining bronchus and not by a check-valve mechanism. In addition, serial CT scans of our patient revealed growing cavitary lesions, with destruction of partitions, and pulmonary parenchyma.
Bronchoscopy is useful for the diagnosis and assessment of the treatment efficacy of large cavitary M. avium pulmonary infection. To fully understand the evolution of cavity formation in MAC infections, more cases should be studied by serial observation using bronchoscopy.
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