A 46-year-old man with no history of smoking was referred to our hospital in 2008 because of abnormal opacities on chest radiographs that were obtained at a local clinic where he had been treated for bronchial asthma. He had worked in an aluminum-processing factory for the past 6 years, from 1996 through 2001, where he had been exposed to aluminum dust. Beryllium was not used. He had not worn a protective mask. He had no signs of cough, dyspnea, fever, skin involvement, or arthritis. His past medical history included tuberculosis in childhood, gallstones at 21 years of age, and bronchial asthma at 43 years of age. His medications included theophylline, montelukast, olopatadine, beclometasone dipropionate, and fenoterol hydrobromide. With regard to family history, his mother had had tuberculosis.
Physical examination revealed a well-developed, well-nourished man. Chest auscultation revealed no abnormal findings, and there was no evidence of uveitis, cervical or supraclavicular lymphadenopathy, arthralgia, skin eruption, or muscle weakness.
Laboratory investigations showed the following values: WBC count 6280/mm3 with 0.6% eosinophils, Hb 16.8 g/L, C-reactive protein 0.1 mg/dL, aspartate aminotransferase 17 U/L, alanine aminotransferase 17 U/L, lactate dehydrogenase 195 IU/L, Upsilon-glutamyl transferase 21 U/L, creatinine 0.60 mg/dL, ACE 15.3 U/L, serum KL-6 291 U/mL, and SP-D 25.0 ng/mL. QuantiFERON TB-2G testing (Cellestis, Carnegie, Australia) was positive with culture filtrate protein-10 of 5.14 IU/mL, and the 6-kDa early secretory antigenic target of Mycobacterium tuberculosis was 0.20 IU/mL (normal range <0.35 IU/mL). PPD skin testing was positive for indurations of 27 mm x 24 mm. Arterial blood gas analysis while breathing room air did not reveal hypoxemia (PaO2 90.3 Torr), with PaCO2 39.7 Torr and pH 7.433. Pulmonary function tests showed the following values: VC 3.05 L (83.7%) and forced expiratory volume in 1 s 2.53 L (78.6%). Diffuse nodular shadows were found on chest X-ray (Fig. 4A), and chest HRCT showed diffuse nodular opacities with interlobular septal thickening (Fig. 4B). In BAL fluids there were 3.1 x 105 cells per mL, with 1.0% neutrophils, 18.5% lymphocytes, and 80.5% macrophages. The ratio of CD4 to CD8 T lymphocytes was 0.94. BAL fluid cultures and acid-fast bacillus PCR were free of pathogens. Histology performed on transbronchial biopsies did not reveal granuloma and no definite diagnosis could be made. Anti-tuberculosis drug therapy using rifampicin, isoniazid, ethambutol, and pyrazinamide for 3 months did not improve the chest HRCT findings. Then a video-assisted lung biopsy was performed. Results of histology of tissue obtained from the right S3 region are shown in Fig 5. Granulomatous lesions mainly composed of multinucleated giant cells were observed predominantly in the pulmonary interstitium. Results of microscopic examination of the tissue with special stains for mycobacteria and fungi were negative. Hemosiderosis and anthracosis with pneumoconiotic materials were also observed (not shown). Elemental analysis was performed for the granuloma (Fig. 6A) and the centrilobular fibrosing lesion (Fig. 6C). Silicon, aluminum, iron, and titanium were detected in both lesions (Table 1 Site 3 and 4). Especially wide distribution of aluminum was observed in the granuloma (Fig. 6B).
The patient was followed up without special medication though 2014 when his chest HRCT findings showed no changes and he was without respiratory symptoms.