A 36-year-old female patient was admitted to our hospital due to chronic cough, expectoration, chest tightness and wheezing. She is a never smoker. She had experienced chronic sinusitis since the age of 12 and started experiencing cough and purulent sputum at the age of 20. The symptoms progressively worsened, presenting with exertional dyspnea and constant wheezing. At the age of 25, the patient underwent “thoracotomy drainage and biopsy” in the local hospital due to “empyema and pleural effusion.” Physical examination on admission revealed diffuse expiratory wheezes and coarse crackles in both lungs. Pulmonary function test showed that the ratio of the forced expiratory volume in 1 second to the forced vital capacity (FEV1/FVC) was 43.39% (). Blood gas analysis showed hypoxemia with an oxygen partial pressure (PaO2) of 62 mmHg and oxygenation index of 155 mmHg. Chest high-resolution computed tomography (HRCT) scan showed well-defined multiple centrilobular nodules and diffuse tree-in-bud pattern (). No obvious abnormalities were found in routine blood tests, procalcitonin, sputum smear microscopy, sputum culture, tuberculosis bacili gamma interferon release test, rheumatoid factors, humoral immunity, connective tissue related antibodies, anti-neutrophil cytoplasmic antibody, etc. On the first admission, the patient’s symptoms improved after symptomatic treatment such as antitussive, expectorant and antiasthmatic treatment and discharged from the hospital automatically.\nHowever, the patient presented with the above symptoms repeatedly and was hospitalized in our hospital again after 1 month. On this admission, we performed further investigations on this patient. Paranasal sinus CT showed bilateral maxillary sinus inflammation (). Cold agglutinin level was in the normal range. A diagnosis of diffuse panbronchiolitis was made given the symptoms, signs, history of sinusitis, radiological, pulmonary function and laboratory findings. In this hospitalization, we treated the patient with azithromycin (500 mg per day), and the respiratory symptoms of the patient were obviously improved. However, dyspnea symptoms of the case 1 were not well controlled, so we treated the patient with prednisone acetate for 12 months. The dose was gradually reduced from 30 mg to 10 mg per day and finally stopped.\nSince then, the patient has been followed up at our hospital for 2 years, sometimes hospitalized for deterioration of her condition. Sixteen months after the definite diagnosis, the patient was hospitalized again in our hospital for cough, expectoration and dyspnea. Chest CT showed a small nodule at the upper tip of the right lung (). Sputum culture showed a small amount of Pseudomonas aeruginosa growth (++). Fiberoptic bronchoscopy revealed abundant purulent secretions in the left and right main bronchi and all levels of bronchi (). Bronchoalveolar lavage fluid culture showed that Pseudomonas aeruginosa was 300 colony-forming units per milliliter (CFU/ml). The second bronchoscope lavage fluid smear revealed 1 root of acid-fast bacilli/300 visual field, and the culture showed a small amount of fusarium. Mycobacterium tuberculosis complex group DNA was positive. The patient was diagnosed as secondary pulmonary tuberculosis and received anti-tuberculosis treatment with isoniazid, rifapentine, ethambutol and moxifloxacin. Since then, the patient has received anti-tuberculosis treatment for up to 12 months. The patient’s condition gradually improved and the nodule in the right lung showed significant shrinkage () after anti-tuberculosis treatment.
A 76-year-old man was admitted to our hospital because of one-month history of dyspnoea on exertion, cough, and viscous sputum. He has been diagnosed with asthma since he was 62 years, and has been partially controlled (score 20 in Asthma Control Test) with inhaled corticosteroids/long-acting β2 agonist (ICS/LABA). When he was 75 years old, he noticed lymphadenopathy, and was diagnosed with follicular lymphoma. He received six courses of rituximab combined with pirarubicin-cyclophosphamide, vincristine and prednisolone (R-THP-COP) therapy, and a complete remission was achieved. After the chemotherapy, he noticed shortness of breath, cough, and viscous sputum. As chest computed tomography (CT) revealed diffuse granular shadows in bilateral lungs, he was referred to our hospital. He had a surgical history of chronic sinusitis at 28 years of age, and had a 30-pack-year history of smoking until the age of 62. Physical examination revealed hypoxia, peripheral capillary oxygen saturation (SpO2) 92% with a low-grade fever. Auscultation of the lungs showed coarse crackles and wheezes in both lung fields. On laboratory findings, white blood cell counts increased to 8670/μL with neutrophilia (72.6%). C-reactive protein level was 7.82 mg/mL. Pseudomonas aeruginosa was detected in sputum culture. The level of total immunoglobulin E was 288 IU/mL, and a titre of cold agglutinin was >64. Fibre-optic bronchoscopy was performed to evaluate the shadows; the cellularity of bronchoalveolar lavage fluid (BALF) was increased to 1.91 × 105/mL with increased proportion of both neutrophils (86.4%) and eosinophils (8.2%). Transbronchial lung biopsy revealed mild infiltration of lymphocytes, plasma cells, and foamy macrophages around the respiratory bronchioles, which was compatible with DPB, and goblet cell hyperplasia with thickness of basement membrane, which was compatible with asthma (Fig. ). As he fulfilled the diagnostic criteria for DPB, we started low-dose macrolide therapy. After erythromycin (400 mg/day) was added to ICS/LABA, his symptoms reduced, along with the improvements in pulmonary function, diffuse granular shadows, and airway clearance determined by saccharin test (Table ). Conversely, the level of fractional exhaled nitric oxide (FeNO), a biomarker of eosinophilic airway inflammation, increased 2 weeks after the macrolide therapy. The level of FeNO then gradually decreased (Table ).