A 72-year-old female presented with recurrent cough, yellow phlegm and intermittent hemoptysis for over 8 years. Initially, the patient began coughing frequently after a cold with purulent sputum, occasionally with blood-tinged sputum or mild hemoptysis. She was diagnosed with bronchiectasis after a chest computed tomography (CT) examination by local hospital eight years ago. Previous medical records indicated that no fungi were detected in bronchoalveolar lavage (BAL) fluid and sputum. Pulmonary symptoms were usually reduced or alleviated by empirical broad-spectrum antibiotics (levofloxacin, ceftriaxone/tazobactam, biapenem) for about one week and hemostatic therapy (Yunnan Baiyao Capsule, a traditional Chinese medicine) as needed. However, due to progressive aggravation of cough and purulent sputum, gradually appearance of breathlessness and chest tightness for the last two years, and most importantly, increased volume of hemoptysis from less than 10ml at the beginning to occasionally 30-60ml/24h, the patient admitted for further investigation in April 2019. The main symptom on admission was cough with purulent sputum accompanied by bright red blood, about 4-8 times a day and 5-10ml each time. Fever, chills, night sweat, rash or joint pain were denied. The patient reported a history of tuberculosis 10 years ago, and recovered after one year of anti-tuberculosis drug treatment. Beyond that, smoking or drinking were denied, nor did she have a history of hypertension, diabetes, cancers, chronic hepatitis, or blood disease.
At the time of admission, physical examination revealed a thin woman with normal vital signs. The breath sounds of both lungs were coarse, bibasilar crackles were auscultated especially in the right lung. No rhonchi or wheezes. Blood routine suggested mild anemia (hemoglobin 9.8g/dL) with normal white blood cell count. As for inflammatory markers, the level of procalcitonin (PCT) was less than 0.05ng/mL, both erythrocytes sedimentation rate (ESR, 26 mm/h) and hypersensitive C-reactive protein (hs-CRP, 2.1mg/L) were increased slightly. No significant abnormalities were found in blood coagulation function, liver and kidney function, and anti-neutrophil cytoplasmic antibody. Chest CT indicated bronchiectasis accompanied by infection in the middle and lower lobe of the right lung, multiple patchy infiltrates of both lungs with increased mediastinal lymph nodes (Fig. 1A,B,C). Fiberoptic bronchoscopy before antibiotic administration (Fig. 2) showed a few dark red blood stains and a lot of purulent secretions in the bilateral bronchus, especially in the right middle lobe and the left superior lobar bronchus. After aspiration, the lumen was unobstructed and the mucosa was smooth. BAL fluid from the right middle bronchus was incubated on slants of Sabouraud 's dextrose agar, many white velvety and brownish-gray pigmented colonies grew after 10 days incubation (Fig. 3). Fungal PCR using 28S rDNA primers identified Microascus cirrosus. Sputum and BAL cultures grew normal flora, with no evidence of viral, mycobacterial, or additional fungal pathogens isolated; likewise, blood cultures remained negative. T-spot test and MTB/RIF GeneXpert detection assays were negative. Both galactomannan enzyme-linked immunosorbent assays and 1,3-beta-D-glucan tests were negative in serum and BAL fluid.
Given these findings, the patient was diagnosed with a pulmonary fungal infection with bronchiectasis. So intravenous (oral after discharged) voriconazole 200 mg twice daily and aerosolized amphotericin B 12.5mg twice daily were initiated for empiric treatment in April 2019. The blood concentration of voriconazole when administered orally was 2.1 mug/mL (therapeutic window: 2-6 mug/mL). While on combinational antifungal treatment, the patient presented resolution of hemoptysis, as well as remission of cough, wheezing and chest tightness. Two months later, chest CT demonstrated a slight improvement (Fig. 1D,E,F). Repeat bronchoscopy on Day 77 denoted no distinct abnormality in the visible areas of bilateral bronchi, although BAL fluid grew mold identified again as M. cirrosus. No obvious side effects to liver function were observed in the first three months, but aspartate aminotransferase and gamma-glutaminase elevated 2-3 times on Day 93. The antifungal drugs were withdrawn and pulmonary symptoms did not relapse. Liver function returned basically normal three weeks later. The level of hemoglobin increased from 9.8g/dL to 10.9g/dL two months later and remained at 10.9g/dL after antifungal therapy was discontinued (on Day 102). Moreover, there was no radiologic progression during another 3 months (Fig. 1G and H,I) and one year (Fig. 1J,K,L) of follow-up.
CT images of the patient. CT images indicated bronchiectasis in both lungs, multiple calcified nodules and patchy infiltrates in the right lung before treatment (A,B,C).