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Abstract Background Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP). Methods We reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). Results The expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP. Conclusion Our results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen.

We reported 3 cases of hypersensitivity pneumonitis who had been exposed to polyurethane material containing diphenylmethane diisocyanate (MDI) for 1-12 weeks. They had cough, fever and dyspnea before admission. All 3 cases were diagnosed immunologically using anti-MDI antibodies. Chest HRCT findings of the 3 cases were different. Case 1 showed an organizing pneumonia (OP) pattern : patchy peripheral consolidation with air bronchogram and ground-glass opacities (GGO), and case 2 showed a nonspecific interstitial pneumonia (NSIP) pattern : consolidation and reticular shadows in both lower lobes. In addition, case 3 showed a hypersensitivity pneumonitis (HP) pattern : centrilobular GGO and diffuse granular shadows. All cases were successfully treated by corticosteroids alone. This suggests that different amounts of inhaled antigen can cause different HRCT findings.

We report two cases of pleomorphic carcinoma with fever and severe inflammatory reaction. In case 1, an abnormal mass shadow was found on the chest X-ray film of a 63-year-old man with bloody sputum. After right upper lobectomy, the tumor was diagnosed as pleomorphic carcinoma. About 7 months after surgical operation, he had fever and chest pain. Although his test results showed leukocytosis and his elevated serum CRP level indicated some infection, there were no signs of bacterial or fungal infection. Further examination revealed metases of lung cancer in the left adrenal gland, mediastinal and iliac lymph nodes. Serological study revealed elevated level of G-CSF, likely due to G-CSF producing metastatic tumors. In case 2, a 77-year-old man presented with continuous high fever. Examinations revealed elevated serum CRP level and multiple nodular shadows and enlarged supraclavicular and mediastinal lymph nodes on the chest CT, suggesting some infectious, connective tissue, or lymphoproliferative diseases. He was finally found to have pleomorphic carcinoma of the lung by histological examination of lymph nodes. The continuous high fever seemed to be a tumor-related fever, because it rapidly disappeared after administration of naproxen.

A 32-year-old woman was admitted to our hospital because of fever and back pain. Two months previously, she had been given a diagnosis of bacterial pneumonia based on the same symptoms and recovered after antibiotic treatment. Chest CT scans on admission showed a consolidation and thickened pleura in the right lower lobe. Bronchoalveolar lavage fluids showed an alveolar hemorrhage. Lung biopsy specimens showed thickened pulmonary arteries and fibrotic nonspecific interstitial pneumonia (NSIP). Three years later, she was admitted with fever and pain of the left arm and aortitis syndrome was diagnosed. In this case of NSIP pattern associated with aortitis syndrome we speculate that repeated pulmonary infarction and alveolar hemorrhages caused the NSIP pattern.

A 37-year-old woman admitted elsewhere for a high fever, dry cough, stridor, and dyspnea was found in chest radiography and computed tomography on admission to have a thickened bronchial wall with centrilobular nodules in both lower lobes and skipped consolidations in the lower and middle lobe of the right lung. She had been diagnosed with mycoplasmal pneumonia because of high Mycoplasma pneumoniae antibody titer, so clarithromycin (CAM) was administrated. She was referred to us due to hypoxia with obstructive impairment in the pulmonary function test. Ventilation/perfusion radioisotope in the lung scan indicated heterogeneous distribution without mismatch, suggesting bronchiolitis obliterans due to M. pneumoniae pneumonia, so steroids were started. Five weeks of steroid administration ameliorated clinical symptoms, hypoxia, and abnormal shadows, but obstructive impairment diod not disappear completely. Early administration of steroid with antibiotics is required for bronchiolitis obliterans caused by M. pneumoniae. We review cases of mycoplasmal bronchiolitis reported in Japan.

Defensins are endogenous antibiotics and regulators of inflammation, immunity and wound repair. Their concentrations are substantially increased in bronchoalveolar lavage fluid (BALF) of patients with infectious lung diseases. alpha-defensin (HAD) levels are also elevated in patients with idiopathic pulmonary fibrosis (IPF) and correlated with the decline in pulmonary function tests, suggesting the association of defensins with the pathogenesis of interstitial lung diseases. The aim of this study was to determine the profile of defensins in interstitial lung diseases. Serum and BALF levels of HAD and beta-defensin 1 and 2 (HBD-1, and -2) were measured by radioimmunoassay in 63 patients with interstitial lung diseases, including idiopathic pulmonary alveolar proteinosis (PAP), IPF, nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) and pulmonary sarcoidosis, and in 9 healthy volunteers as controls. Levels of HAD in BALF of patients with PAP were significantly higher than those in controls and patients with COP and sarcoidosis. Serum levels of HAD in all groups were significantly higher than those in controls. Levels of HBD-1 and -2 in BALF of patients with PAP were extremely high in all subjects. Serum levels of HBD-1 were higher in all patient groups, with the exception of those with PAP, and those of HBD-2 were also higher in patients with IPF and sarcoidosis, compared with controls. BALF of PAP patients, but not IPF patients and controls, expressed antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Our findings suggest different kinetics of HAD and HBD-1 and -2 in serum and BALF of interstitial lung diseases and that these antimicrobial peptides in the airway lumen may contribute to prevention of bacterial airway infections in PAP.

A 15-year-old girl was admitted to our hospital because of polydipsia, polyuria, bilateral hilar lymphadenopathy and uveitis. A diagnosis of sarcoidosis with central diabetes insipidus was made by radiological, serological, bronchoalveolar lavage examinations, fluid restriction test and vasopression test. Prednisolone therapy improved all of her clinical findings except diabetes insipidus. So she had to continue intranasal 1-desamino-8-arginine vasopressin (DDAVP) therapy. In addition, we reviewed the clinical features of 27 patients of sarcoidosis with diabetes insipidus reported in Japan. They included 12 patients in young men and 21 patients having uveitis. These patients showed low frequency of lung complications in comparison with sarcoidosis without diabetes insipidus. Steroid therapy improved the symptoms of diabetes insipidus in only 3 patients, and all these 3 patients started steroid therapy within 1 month after the onset. Therefore we think that early diagnosis and treatment are important. Though central neurosarcoidosis was generally considered to have poor prognosis, there were only 3 patients who had recurrence by steroid tapering.

Objective and Background: Interferon gamma-inducible protein (IP)-10 and epithelial neutrophil-activating peptide (ENA)-78 belong to the CXC chemokine family and are important factors in inflammatory lung diseases. In sarcoidosis, the potential role of IP-10 to regulate the migration and activation of T-cells towards sites of sarcoid activity has been suggested., Methods: In this study, the concentrations of IP-10 and ENA-78 in the serum and BAL fluid of patients with different stages of active pulmonary sarcoidosis (n=41) and healthy subjects (n=12) were measured by enzyme-linked immunosorbent assay to evaluate the contribution of these CXC chemokines to this disease., Results: Serum and BAL fluid concentrations of IP-10 and BAL fluid levels of ENA-78 in patients with sarcoidosis were significantly higher than those in control subjects. The serum levels of IP-10 were significantly increased only in patients with stages I and II sarcoidosis, while BAL fluid levels of ENA-78 were increased only in stage III sarcoidosis. In addition, serum concentrations of IP-10 were elevated in patients with extrapulmonary lesions compared with those without such lesions. In patients with sarcoidosis, IP-10 concentrations in BAL fluid correlated with lymphocyte proportions in BAL fluid., Conclusion: IP-10 may play an important role in regulating lymphocytes into the lung and that ENA-78 may be associated with lung parenchymal disease in pulmonary sarcoidosis.

SELAPINA is generic product of PL granule which is one of the most common forms of combination remedies for the common cold in Japan, and includes acetaminophen. We report a case of SELAPINA-induced pneumonia successfully treated with glucocorticoid pulse therapy followed by orally administered prednisolone. A 68-year-old woman, who had been treated for rheumatoid arthiritis with pulmonary involvement, took SELAPINA with an antibiotic for 6 days because of her cold symptoms. She then suffered a high fever, cough, dyspnea, vomiting and diarrhea. Chest radiograph and high-resolution computed tomography (HRCT) scan revealed diffuse interstitial shadows. SELAPINA-induced pneumonia was diagnosed because the blastoid transformation test using her peripheral blood lymphocytes was positive on stimulation with SELAPINA, but negative for other medicines.

We report here 3 cases of chronic bird fancier's lung diagnosed immunologically using antibodies to pigeon dropping extract. None of the patients were bird fanciers but had indirect exposure to birds in their living environment, and had been using feather-filled duvets or pillows for a long time. Two of 3 cases were positive for environmental provocation tests and 2 cases had pathological findings of hypersensitivity pneumonitis such as multinucleated giant cells and non-necrotizing epithelioid cell granulomas. One case was resistant to steroid therapy alone and was successfully treated by coadministration of prednisolone and cyclosporin A. Another case was treated by steroid alone but died of acute exacerbation of unknown cause. These cases suggest that not only feathers but two or more kinds of bird-related antigens were involved in the sensitization immunology and development of bird fancier's disease, and that clinicians should perform thorough history taking with environmental surveillance relevant to birds.

A 29-year-old woman was admitted to our hospital because of persistent breathlessness on exertion after the delivery of her second child. Although at the age of 26 she had been given a diagnosis of multiple pulmonary arteriovenous fistula (PAVF), treatment was not done because of the absence of symptoms. An intrauterine growth retardation (IUGR) due to hypoxemia occurred during the second pregnancy, and then she delivered a 1,283g baby by cesarean section in the 36th gestation week. Her symptoms and hypoxemia improved after transcatheter embolization. Hereditary hemorrhagic telangiectasia was diagnosed on the basis of recurrent epistaxis since her childhood, pulmonary and hepatic vascular abnormality (PAVF and hepatic arterioportal shunt) and telangiectasis of the buccal mucosa and tongue. We should consider an early treatment of PAVF for young female because pregnancy may induce increase of arteriovenous shunt, fatal hemoptysis, infertility, miscarriage and IUGR.

A 37-year-old-woman was admitted to our hospital because of chest bilateral reticular shadow with fever, cough, general malaise and exertional dyspnea in the summer. A diagnosis of summer-type hypersensitivity pneumonitis (SHP) was made by radiological, serological and histological examinations. Her 10-year-old daughter had chest reticular shadows and similar symptoms. These two patients were positive for serum anti-Trichosporon cutaneum (T. asahii, T. mucoides) antibodies and T. asahii was identified from cultured samples obtained from their house. They recovered spontaneously after hospitalization or isolation from the antigen. We reviewed the clinical features in sixteen families with familial SHP reported in Japan. Children aged under 15 years old accounted for 34% and there was no gender difference among patients. This finding differs from the conventionally defined features of patients with SHP. Measurements of serum KL-6, SP-D and SP-A seem to be useful for auxiliary diagnosis and monitoring the disease activity of SHP, especially in pediatric cases who cannot undergo invasive evaluation.

A 59-year-old woman was admitted because of general fatigue, cough and progressive dyspnea about 5 months after treatment with simvastatin for hyperlipidemia. A chest radiograph and computed tomography scans revealed ground glass and reticular opacities in the right middle and lower lung fields. The percentage of peripheral blood eosinophils was elevated. After simvastatin was discontinued and administration of prednisolone was started, eosinophilia and reticular shadows improved. Drug lymphocyte stimulation test (DLST) for simvastatin was positive, so we diagnosed drug induced eosinophilic pneumonia. Now hyperlipidemia is treated frequently with HMG-CoA reductase inhibitor, but there are few reports demonstrating lung injury by this drug. We should be aware of lung side effects of HMG-CoA reductase inhibitor.

A 56-year-old woman presented with complaints of general malaise and left chest pain. Chest radiography and CT scanning revealed multiple nodules and infiltrations in both lung fields. Her symptoms diminished and the extent of some of the lung shadows decreased spontaneously. However, since new shadows appeared later in other parts of the lung, she was admitted to our hospital on September 3. A transbronchial lung biopsy was not adequate for diagnosing a particular disease. But thoracoscopic lung biopsy specimens revealed necrosis with localized pleural fibrosis, and so a diagnosis of pulmonary infarction was made. The patient did not have any underlying disease or coagulation abnormalities, but Sjögren's syndrome and an antipsychotic agent were suspected to be background factors.

A 53-year-old woman visited our hospital in July 2002 with complaints of skin eruptions on the face and extremities, dry cough and dyspnea. A diagnosis of amyopathic dermatomyositis (ADM) was made on the basis of characteristic skin lesions and skin biopsy findings with slight muscle symptoms and mild elevation of muscle enzymes. Interstitial shadows were observed in both lower lung fields on chest radiographs, and thoracoscopic lung biopsy specimens revealed a diffuse alveolar damage (DAD) pattern. After induction of chemotherapy with prednisolone (50 mg/day) and cyclosporin A (150 mg/day), the respiratory symptoms and interstitial shadows were gradually reduced. Although it is known that interstitial pneumonia has an acute course and poor prognosis in ADM, the present case responded well to the chemotherapy with prednisolone and cyclosporin A.