TGFB1 promoter polymorphism C-509T and pathophysiology of asthma.

BACKGROUND: TGF-beta1 can modulate airway inflammation and exaggerate airway remodeling. A polymorphism of a promoter region of TGFB1, C-509T, might be associated with the development of asthma, but its pathophysiologic relevance remains poorly understood. OBJECTIVE: We investigated relations of the C-509T polymorphism to airflow obstruction, sputum eosinophilia, and airway wall thickening, as assessed by means of computed tomography, in 85 patients with stable asthma. METHODS: The CC, CT, and TT genotypes were examined by means of PCR and restriction enzyme fragment length polymorphism. At a selected bronchus, 3 indices of airway wall thickness were measured with an automatic method. RESULTS: The CC, CT, and TT genotypes were found in 22, 46, and 17 patients, respectively. Serum TGF-beta1 levels were significantly associated with the polymorphism and were increased in the CT/TT genotypes. FEV(1) and sputum eosinophil percentages were also significantly associated with the polymorphism and were both decreased in the CT/TT genotypes. The polymorphism was unrelated to airway wall thickness. CONCLUSION: In addition to increased serum TGF-beta1 levels, the T allele of the C-509T polymorphism is related to increased airflow obstruction but attenuated eosinophilic inflammation. The former relation is not attributed to thickening of the central airway walls. The latter relation might reflect the anti-inflammatory effect of TGF-beta1. The C-509T polymorphism has a complex role in asthma pathophysiology, presumably because of the diverse functions of TGF-beta1 and its various interactions with cells and humoral factors in vivo.

[A case of drug-induced pleuritis, possibly due to Hochuekkito].

We report a case of drug-induced pleuritis possibly due to Hochuekkito. Hochuekkito, a Chinese-Japanese herbal medicine, was prescribed for a 33-year-old woman with panic disorder and depressive state. About 10 weeks after the first administration, she was admitted complaining of chest pain and cough. Chest X-ray and computed tomography showed the right pleural effusion. Thoracocentesis revealed eosinophilic pleuritis. Discontinuation of Hochuekkito resulted in improvement of the clinical findings. Based on the clinical course, we considered this case to be Hochuekkito-induced pleuritis.

[A case of cryptogenic organizing pneumonia accompanied by large bullae].

A 66-year-old man complaining of fever was given intravenous antibiotic therapy, but he did not improve. After subsequent admission, chest X-ray film and computed tomography scans showed large bullae and consolidation in the right lung field. A transbronchial lung biopsy specimen revealed infiltration of mononuclear cells in alveolar septa and organizing lesions in alveolar ducts. We considered this case to be cryptogenic organizing pneumonia (COP) from its clinical course and pathological findings. Treatment with corticosteroid resulted in disappearance of the large bullae and consolidations. COP accompanied by large bullae is very rare. The large bullae may have been caused by check-valve mechanism.

[A case of pulmonary adenocarcinoma accompanied by minimal change nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia].

A 49-year-old man was urgently admitted due to edema in both leg and left toe pain. A chest radiograph revealed a solitary nodule in the right lung field. Detailed investigations including bronchoscopy and renal biopsy led to a simultaneous diagnosis of clinical stage IIIB pulmonary adenocarcinoma, minimal change nephrotic syndrome, antiphospholipid syndrome, and warm-type autoimmune hemolytic anemia. Prednisolone was administered for nephrotic syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia, and 6 courses of chemotherapy with 70Gy radio-therapy were performed. The pulmonary nodule significantly decreased in size and the other three autoimmune diseases appeared to be well-controlled. Thirteen months after admission, multiple brain metastases developed along with worsening antiphospholipid syndrome symptoms including lupus anticoagulant. Following whole-brain irradiation, the brain metastases decreased in size and antiphospholipid syndrome symptoms improved. Thirty-nine months after the initial visit, the primary lung cancer, its brain metastasis and the 3 other autoimmune diseases appeared to be well-controlled. The temporal correlation of the lung cancer and the three autoimmune diseases suggests the latter may be paraneoplastic syndrome.

[Pleurodesis using autologous blood plus OK-432 for intractable spontaneous pneumothorax with high surgical risk].

Air leakage persisted from the lung in three cases of spontaneous pneumothorax. Pleurodesis with autologous blood ended in failure. Autologous blood plus OK-432 was instilled into the thoracic cavity from the chest drainage tube. Air leakage was stopped without serious side effects and the chest tube was removed uneventfully. Although the long-term outcome of this treatment is not known, pleurodesis using autologous blood plus OK-432 may be an effective way of treatment for spontaneous pneumothorax in cases with high surgical risk.

[Clinical evaluation of bird related hypersensitivity pneumonitis].

We retrospectively evaluated 8 cases of bird related hypersensitivity pneumonitis in Tenri hospital, all of whom underwent surgical lung biopsy. They had a history of contacting with birds and had serological studies using lymphocyte stimulation test to pigeon serum or antibody in serum and bronchoalveolar lavage fluid to pigeon dropping extracts yielded positive results. Computed tomography revealed a radiographic pattern unlike typical UIP. The result of pathological diagnosis of surgical lung biopsy was 'others' or NSIP pattern. Only one case had pathological findings of granuloma. Four cases had an improved or stable course only offer segregation from bird antigens. The other four cases needed corticosteroids and immunosuppressants, and two of the four cases had a progressive course and died of respiratory failure.

[A case of small cell lung cancer with an initial symptom of breast metastasis].

We report a case of small cell lung cancer with an initial symptom of breast metastasis. A 55-year-old woman was admitted complaining of multiple breast masses. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a left hilar mass. Specimens obtained from a breast mass and transbronchial biopsy revealed neoplastic cells suggesting small cell carcinoma Small cell lung cancer with breast metastasis was diagnosed. Systemic chemotherapy resulted in partial remission of the primary lesion and breast metastases.

Interstitial pulmonary edema revealed by high-resolution CT after relief of acute upper airway obstruction.

We report a case of acute pulmonary edema appearing soon after relief of an acute upper airway obstruction. The patient choked on some pieces of beef during dinner and fainted. He was quickly aided by paramedics and taken to our emergency room with persistent dyspnea and wheezing. His chest radiograph showed bilateral pulmonary edema predominantly distributed in the upper lung field, and high-resolution CT (HRCT) revealed that the pulmonary edema was mainly in the interstitium. The patient recovered uneventfully. HRCT clearly disclosed the characteristics of pulmonary edema of acute upper airway obstruction.

[Autopsy case of pulmonary aspergillosis soon after convalescence from pulmonary tuberculosis].

A 70-year-old man with liver cirrhosis and previous gastrectomy admitted for fever, coughing, and bloody sputum soon after convalescing from pulmonary tuberculosis had a peripheral white blood cell count of 9,900/microL, C-reactive protein of 14.1mg/dL, serum albumin of 2.0g/dL, and serum positive for antiaspergillus and beta-D glucan antibodies. Chest radiography showed thickening of the walls of the large residual cavities with previous tuberculosis lesions and infiltrates around them. On day 2 of hospitalization, Aspergillus fumigatus without other bacillus was detected in sputum culture taken on admission. Despite immediate treatment with intravenous micafungin and oral itraconazole and improved brief initial improvement, his general condition abruptly deteriorated into frequent massive hemoptysis and he developed of shock, respiratory failure, and severe malnutrition, dying 30 days later. Autopsy findings showed pulmonary aspergillosis in and around the large cavities and on the other side of the lungs. Pulmonary aspergillosis without hematological malignanciy and immunosuppression can thus be abruptly severe and fatal due to malnourishment stemming from pre-existing conditions such as chronic hepatitis despite prompt, ordinarily adequate medical treatment.

[Three sisters of pulmonary Mycobacterium avium complex disease].

We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.

[An adult case of cervico-mediastinal lymph nodes tuberculosis followed by the development of pulmonary lesions during the treatment with antituberculous drugs].

A 27-year-old man was admitted to our hospital due to a painful mass in the right neck and fever. Cervical and superior mediastinal computed tomography showed an enlargement of right supraclavicular lymph node and multiple swollen mediastinal lymph nodes, including low-density areas and contrast medium-enhanced septa and margins. Smears of the pus obtained from right supraclavicular lymph node showed acidfast bacilli identified as Mycobacterium tuberculosis by PCR method. He was treated with antituberculous drugs with INH, RFP, EB, and PZA. PZA was given for initial two months. Six months later, productive cough developed and chest X-ray films showed infiltrative shadow in the right upper lung field. One month after the onset of cough, bronchoscopy revealed a polypoid lesion with a white coating in the right main bronchus. Microscopic examination of the specimen obtained by transbrochial biopsy revealed many epithelioid cell granulomas, consistent with tuberculosis. From these findings, pulmonary lesion was suggested to be due to invasion of the mediastinal lymph node into the bronchus. After one year of antituberculous chemotherapy, the swelling of the cervical-mediastinal lymph nodes was reduced and the abnormal chest X-ray shadows disappeared.

[Case of drug-induced pneumonia possibly due to mefloquine (antimalarial drug)].

A 59-year-old man took mefloquine (antimalarial drug), total dose of 1,000 mg, to prevent malaria before and during traveling to South Africa. Three weeks after the first administration, he was admitted complaining of fever and dyspnea. Chest HRCT showed ground-glass opacities and consolidation in both lung fields. Withdrawal of mefloquine and treatment with corticosteroid resulted in improvement of the clinical findings. From the clinical course, we considered this case to be mefloquine-induced pneumonia. Mefloquine may have caused pulmonary toxicity.

Bronchial dilatation in asthma: relation to clinical and sputum indices.

BACKGROUND: Investigations using high-resolution CT (HRCT) show that bronchial dilatation (BD) is found in many patients with asthma. However, the pathogenesis and pathophysiologic relevance of BD in asthma are poorly understood. A balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may control the remodeling of extracellular matrix, and excess MMPs have been associated with destruction or dilatation of airways in patients with bronchiectasis. OBJECTIVES: To study the prevalence of BD as assessed by HRCT according to standard subjective criteria in 37 patients with stable asthma and 10 healthy control subjects, and to examine the relation of BD in asthmatic patients to clinical characteristics and sputum indices, including MMP-9 and TIMP-1 levels. DESIGN: A prospective cohort study. RESULTS: At least one dilated bronchus was present in 23 asthmatic subjects (62%) and 2 control subjects (20%) [p = 0.030]. The ratio of dilated bronchi to all eligible bronchi in each subject (individual BD%) was higher in the asthmatic patients than in the control subjects (11.4 +/- 16.1% vs 1.3 +/- 3.0%, p = 0.011) [mean +/- SD]. Asthmatic patients with (n = 23) and those without BD (n = 14) were similar with regard to age, duration and severity of asthma, atopy, pulmonary function, sputum eosinophil or neutrophil count, and sputum levels of MMP-9 or TIMP-1 and their molar ratio. Individual BD% of asthmatic patients was also unrelated to these clinical and sputum variables. When analysis was confined to the 23 patients with BD, however, individual BD% correlated with the severity score of asthma (r = 0.49, p = 0.023). The results of follow-up HRCT obtained from 19 patients suggested that BD was a fixed rather than transient phenomenon. CONCLUSION: BD is more prevalent in asthmatic patients than in normal subjects and might be associated with the severity of asthma. Cellular inflammation or possible imbalance between MMP-9 and TIMP-1 was not demonstrated in this study to be related to BD in asthma.

An autopsy case of acute pulmonary toxicity associated with gemcitabine.

Acute respiratory distress syndrome (ARDS) developed following intravenous gemcitabine monotherapy in a 75-year-old man with non-small cell lung cancer. The total dose of gemcitabine was 1,500 mg, and the latent period from starting gemcitabine to pulmonary toxicity was three days. The chest radiographs and high resolution computed tomographic scan revealed bilateral ground-glass opacity. He died on the fourteenth post-chemotherapeutic day due to respiratory failure. Postmortem examination of the lung revealed mixed exudative and fibrotic stages of diffuse alveolar damage. Pulmonary toxicity from gemcitabine can be acute and fatal.

[Therapeutic drug monitoring of cyclosporine MEPC (Neoral) therapy for interstitial pneumonia].

It is widely recognized that the area under the concentration-time curve (AUC) correlates with the clinical effects of cyclosporine MEPC (Neoral) therapy and adverse reactions to it. In this study, we investigated which single blood-level measurement had correlated best with AUC in interstitial pneumonia therapy. Neoral was prescribed in ten cases of interstitial pneumonia. We measured the concentration during the 4 hours following its administration and calculated AUC0-4 (AUC 0-4 hr). The concentration after 2 hours of administration (C2) correlated best with AUC (r2 = 0.71). This result suggests that C2 monitoring would be a better predictor for AUC than C0 (trough level) monitoring in interstitial pneumonia therapy.

[Saprophytic mycosis appearing as a necrotic bronchial tumor and masking lung cancer].

We describe four cases of saprophytic mycosis superficially covering lung cancer to form a bronchial necrotic tumor. Although the first biopsy in each case disclosed mycosis with necrosis, repeated transbronchial biopsy revealed malignant cells. In two of the four cases, we started treatments for lung cancer based on the clinical diagnosis preceding histological diagnosis. Although no treatment to eliminate fungi was performed, all cases showed an uneventful clinical course. It is important not to misdiagnose cancer as a fungal disease on the basis only of a transbronchial biopsy, and to bear in mind this type of saprophytic mycosis.

[A case of juvenile pulmonary infarction associated with diet therapy].

A 31-year-old man experienced chest pain, fever, bloody sputum and cough after diet therapy. Chest radiography and chest CT showed infiltration in the right lower lung field and right pleural effusion. Pulmonary embolism and infarction was diagnosed using 99mTc-MAA perfusion scans and chest enhanced CT. The patient did not have a thrombotic disposition and deep vein thrombosis in the lower extremities. This case did not have an acute onset or dyspnea, and was not typical of pulmonary embolism. The diet therapy may have caused dehydration and acted as a predisposing cause of pulmonary embolism.

[A case of intramedullary spinal cord metastasis due to small cell lung cancer].

A 69-year-old woman was diagnosed with limited stage, small cell lung cancer in February 2001. Systemic chemotherapy and radiotherapy were performed resulting in complete remission of the disease. In October 2001, she complained of pain and numbness of her left arm. Magnetic resonance imaging (MRI) of the neck showed an intramedullary enhanced mass at the C4-5 level. Specimen obtained by tumor biopsy showed pathological diagnosis of metastasis from small cell lung cancer. Neurological symptoms improved after radiochemotherapy. Intramedullary metastasis of lung cancer is very rare, and early diagnosis and multidisciplinary treatment may improve quality of life.

[A case of MPO-ANCA-related vasculitis after asbestos exposure with progression of a renal lesion after improvement of interstitial pneumonia].

A 72-year-old woman was admitted complaining of productive cough. She had worked for an asbestos factory for twenty years. She was positive for MPO-ANCA. The chest HRCT showed interstitial pneumonia without any UIP pattern. A specimen obtained by video-assisted thoracoscopic lung biopsy revealed chronic interstitial pneumonia associated with an asbestos body. Although the interstitial pneumonia improved after the administration of a corticosteroid and an immunosuppressive agent, hematuria and renal dysfunction developed about nine months later. The serum MPO-ANCA titer was elevated and the renal biopsy specimen revealed the presence of vasculitis. As the interstitial pneumonia improved after this treatment, the correct diagnosis may have been, not asbestosis, but MPO-ANCA-related interstitial pneumonia.

[A giant pulmonary aspergilloma managed surgically in an elderly man].

We describe a case of giant pulmonary aspergilloma in a 79-year old man. He had undergone an operation for pulmonary tuberculosis of the right lung at the age of 49 years. His chest ragiograph showed a large fungus ball in the right upper lung field. Taking his age and pulmonary condition into consideration, we performed a cavernostomy and fungus ball resection to prevent life-threatening hemoptysis. The postoperative course was satisfactory and without complication. Cavernostomy may be an alternative choice in high-risk aspergilloma patients.