Serum soluble interleukin-2 receptor as a biomarker in immunoglobulin G4-related disease.

OBJECTIVES: Serum soluble interleukin-2 (IL-2) receptor (sIL-2R) might reflect disease activity in immunoglobulin G4-related disease (IgG4-RD). We aimed to elucidate the clinical significance of blood markers, including sIL-2R, in patients with IgG4-RD. METHODS: We enrolled 59 patients with IgG4-RD and investigated the association between blood markers (white blood cells, C-reactive protein, sIL-2R, IgG, IgG4, IgE, total hemolytic complement), and clinical indices. RESULTS: At baseline, serum sIL-2R (Rs = 0.532, p < .001) and IgG4 (Rs = 0.545, p < .001) levels showed significant correlation to the number of organs involved. During follow-up period (median, 70 months; range, 7-195 months), 40 patients were treated with corticosteroids. Receiver operating characteristic (ROC) analysis showed that baseline sIL-2R levels most accurately predicted patients requiring glucocorticoid treatment (area under the ROC curve, 0.807). Among the 46 patients who improved, sIL-2R and IgG4 levels decreased in 42 and 41 patients, respectively. Among them, serum sIL-2R levels decreased to a normal range in 42 patients (91%), whereas IgG4 levels normalized in 19 (41%). CONCLUSION: The serum sIL-2R level is a potential biomarker for IgG4-RD that may reflect the number of involved organs and may predict patients requiring glucocorticoid treatment.

Thrombomodulin for acute exacerbations of idiopathic pulmonary fibrosis: a proof of concept study.

INTRODUCTION: The mortality of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is high. Anticoagulation therapy (recombinant human soluble thrombomodulin (rhTM)) is recognized as a potential new strategy for treating disseminated intravascular coagulation in Japan. This preliminary study was to evaluate whether the coagulation factors increase or decrease in AE-IPF-patients, and whether the additional administration of rhTM for AE-IPF-patients has any beneficial effects on inflammatory mediators and activated coagulation. METHODS: We retrospectively compared the clinical data of AE-IPF-patients, idiopathic pulmonary fibrosis (IPF) with pneumonia-patients and slowly progressive IPF-patients. As a subsequent study, AE-IPF-patients were prospectively treated with a bolus of rhTM intravenously for six days under mechanical ventilation. We historically investigated the improvement of the serial clinical data in both oxygenation and intravascular coagulation disturbance between treated AE-IPF-patients and untreated AE-IPF-patients. RESULTS: Eleven AE-IPF, 21 IPF with pneumonia and 16 slowly progressive IPF-patients were enrolled, and the coagulatory levels of the AE-IPF-patients were found to be significantly higher than in the other patients. In 20 treated AE-IPF-patients, the 28-day mortality and in-hospital mortality were 35% and 45%, respectively. The levels of oxygenation rapidly increased on day 1 and continued to improve until day 7 in the survival AE-IPF-patients. The thrombin-antithrombin complex levels and inflammatory cytokine levels in the survivors on day 7 were significantly different from those observed in the nonsurvivors. CONCLUSION: AE-IPF-patients were found to have significantly higher levels of coagulation. The rhTM administration in the surviving AE-IPF-patients led to significant differences in the oxygenation and intravascular coagulation disturbance.

Hydrogen peroxide content and pH of expired breath condensate from patients with asthma and COPD.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Analysis of the expired breath condensate (EBC) has been suggested to provide non-invasive inflammatory markers that reflect oxidative stress in the airways. OBJECTIVE: The present study attempts to elucidate whether the hydrogen peroxide (H2O2) levels and pH values in EBC may be useful as biomarkers of the activity or severity of asthma and COPD. METHODS: We measured the H2O2 levels and pH values using a derivatives of reactive oxygen metabolites exhalation test kit (Diacron) and a pH analyser, respectively, in EBC obtained using an EcoScreen from 29 patients with asthma, 33 with COPD, and 33 healthy individuals (all non-smokers). We then examined the relationships among oxidative stress and the asthma control test (ACT) or COPD assessment test (CAT) scores, pulmonary function, fractional exhaled nitric oxide (FeNO), and the extent of low attenuation areas on HRCT. RESULTS: The H2O2 levels were elevated and pH was lower in both asthma (H2O2; 8.75 ± 0.88 µM, p < 0.01, pH; 7.14 ± 0.07, p < 0.05) and COPD (H2O2; 7.44 ± 0.89 µM, p < 0.01, pH; 6.87 ± 0.10, p < 0.01) compared with control subjects (H2O2; 3.42 ± 0.66 µM, pH; 7.35 ± 0.04). Neither the H2O2 levels nor pH correlated with the ACT scores and FeNO in asthma patients. Neither the H2O2 levels nor pH significantly correlated with the pulmonary function in asthma and COPD. However, the CAT scores significantly correlated with the H2O2 levels in patients with COPD (r = 0.52, p < 0.01). CONCLUSIONS: These findings suggest that oxidative stress is involved in the pathogenesis of asthma and COPD and that the H2O2 levels in EBC might reflect the health status in COPD.

Clinical and Pathophysiological Features of High-altitude Pulmonary Edema in the Japanese Population: A Review of Studies on High-altitude Pulmonary Edema in Japan.

High-altitude pulmonary edema (HAPE) is a life-threatening, noncardiogenic pulmonary edema that occurs in unacclimatized individuals rapidly ascending to high altitudes above 2,500 m above sea level. Until the entity of HAPE was first identified in a case report published in Japan in 1966, the symptoms of severe dyspnea or coma occurring in climbers of the Japan Alps were incorrectly attributed to pneumonia or congestive heart failure. The Shinshu University Hospital serves as the central facility for rescuing and treating patients with HAPE in the region. Over the past 50 years, a series of studies have been conducted at Shinshu University to gain a better understanding of the characteristics of HAPE. This review summarizes the major achievements of these studies, including their clinical features, management, and pathogenesis of HAPE, particularly in the Japanese population.

Prediction of requirement for mechanical ventilation in community-acquired pneumonia with acute respiratory failure: a multicenter prospective study.

BACKGROUND: Several severity scoring systems for predicting mortality are established in community-acquired pneumonia (CAP). OBJECTIVES: The predictability of the aggravation such as requirement for mechanical ventilation in addition to mortality was examined in CAP patients with acute respiratory failure by using the age, dehydration, respiratory failure, orientation disturbance and blood pressure (A-DROP) scoring system which was proposed by the Japanese Respiratory Society. METHODS: This study was a prospective, multicenter, observational cohort study. The severity of pneumonia was examined using A-DROP and Pneumonia Severity Index (PSI) which originated from the Infectious Disease Society of America. Requirement for mechanical ventilation and mortality were evaluated for 28 days. RESULTS: 482 CAP patients with acute respiratory failure were enrolled in the study. The 28-day mortality and mechanical ventilation rates were 12.3 and 14.4%, respectively. There were no significant differences in the areas under the receiver-operator characteristic curves for prediction of mortality between A-DROP and PSI (χ² test; p = 0.3613). In the subgroup analyses by severity, the A-DROP scoring system showed a severity-dependent increase of mortality (moderate 5.6%, severe 16.1%, extremely severe 27.1%, Cochran-Armitage trend test; p < 0.0001). Similar results were obtained for mechanical ventilation rate (moderate 9.8%, severe 16.7%, extremely severe 25.4%, Cochran-Armitage trend test; p = 0.0006). The compliance with scoring the A-DROP was higher than that with scoring the PSI (96.9 vs. 71.6%). CONCLUSIONS: The results of this study suggest that the A-DROP scoring system could be a simple CAP risk scoring system which could predict not only mortality, but also the requirement for mechanical ventilation.

Increased human Ca²âº-activated Cl⁻ channel 1 expression and mucus overproduction in airway epithelia of smokers and chronic obstructive pulmonary disease patients.

BACKGROUND: The mechanisms underlying the association between smoking and mucus overproduction remain unknown. Because of its involvement in other airway diseases, such as asthma, we hypothesized that Ca²âº-activated Cl⁻ channel 1 (CLCA1) was associated with overproduction of mucus in the airways of smokers and COPD patients. METHODS: Using real-time quantitative PCR analyses, we compared the CLCA1 mRNA expression levels in induced-sputum cells from COPD patients (n = 20), smokers without COPD (n = 5), and non-smokers (n =13). We also examined the relationship between CLCA1 protein expression and mucus production in lung airway epithelia of COPD patients (n = 6), smokers without COPD (n = 7), and non-smokers (n = 7). RESULTS: CLCA1 mRNA expression was significantly up-regulated in the induced-sputum cells of COPD patients compared with cells of non-smokers (p = 0.02), but there was no significant difference compared with cells of smokers without COPD. Using immunostaining with an anti-CLCA1 antibody, semi-quantitative image analyses of airway epithelium demonstrated significantly increased CLCA1 expression in smokers without COPD (p = 0.02) and in COPD patients (p = 0.002) compared with non-smokers. There were significant negative correlations between CLCA1 protein expression and FEV1/FVC (r = -0.57, p = 0.01) and %predicted FEV1 (r = -0.56, p = 0.01). PAS staining for mucus showed that there was a significant positive correlation between CLCA1 protein expression and mucus production (r = 0.67, p = 0.001). These markers were significantly increased in smokers without COPD (p = 0.04) and in COPD patients (p = 0.003) compared with non-smokers (non-smokers < smokers ≤ COPD). CONCLUSIONS: CLCA1 expression is significantly related to mucus production in the airway epithelia of smokers and COPD patients, and may contribute to the development and pathogenesis of COPD by inducing mucus production.

Potential benefits of early continuous positive pressure ventilation in patients with rapidly progressive interstitial pneumonia.

BACKGROUND AND OBJECTIVE: Rapidly progressive interstitial pneumonia (RPIP), including acute exacerbations of interstitial pneumonia, is associated with high rates of mortality. The present study was performed to examine the effects of respiratory management using non-invasive ventilation (NIV) in patients with RPIP and to assess the prognostic factors for survival. METHODS: BiPAP Vision was used for NIV. Clinical data and information on NIV were retrospectively obtained from patient records. Survival at 30 days was evaluated, and biomarkers were measured after initiation of NIV. RESULTS: Thirty-eight patients who had been admitted with RPIP and treated by NIV were included in the study. The ratio of PaO(2) to fraction of inspired oxygen at initiation of NIV was higher in survivors than in non-survivors (P = 0.0054). The mean duration to initiation of NIV after admission was significantly shorter in survivors than in non-survivors (P = 0.0006). Serum Krebs von den Lungen-6 (KL-6) and LDH levels at the start of NIV were higher in non-survivors than in survivors (KL-6, P = 0.022; LDH, P = 0.044). Bivariate logistic regression analysis showed that early intervention with NIV was a significant predictor of survival at 30 days. In addition, the ratio of PaO(2) to fraction of inspired oxygen and both LDH and KL-6 levels at initiation of NIV were significant predictors of survival. CONCLUSIONS: Early intervention with NIV, mainly continuous positive pressure ventilation, is beneficial for the management of patients with RPIP. A randomized controlled study in a large population is needed to confirm the value of early NIV.

Antimicrobial and anti-inflammatory effects of clarithromycin on Mycobacterium avium complex replication in cultured human bronchial epithelial cells.

The Mycobacterium avium complex (MAC) invades cultured human bronchial cells, can replicate intracellularly, and facilitates the release of inflammatory cytokines and chemokines from cells. The purpose of this study was to examine the effects of clarithromycin (CAM) on MAC invasion, replication, and the release of cytokines and chemokines. A human bronchial epithelial cell line (BEAS-2B) monolayer grown on a tissue culture plate was infected with MAC. After 24 h, the cells were washed with Hanks' buffered salt solution, and extracellular bacteria were killed. The monolayer was further cultured for 5 days in medium containing CAM and subjected to a replication assay. The supernatants were assessed using a microchemotaxis assay and enzyme-linked immunosorbent assay (ELISA). mRNA expression was evaluated using a DNA array. The amount of intracellular MAC on day 5 of culture was significantly lower in the presence of CAM at the levels of 1× and 4× MIC. CAM inhibited the release of chemotactic activity and the production of interleukin (IL)-8 and macrophage chemotactic protein (MCP)-1. DNA array analysis of mRNA expression in BEAS-2B cells showed that CAM inhibited the expression of inflammatory cytokines and chemokines, involving IL-6, MCP-1, and IL-8 mRNA. MAC invaded and replicated in BEAS-2B cells and induced the production of chemotactic factors. In contrast, CAM may have bactericidal and bacteriostatic effects leading to the inhibition of inflammatory events.

Clarithromycin inhibits interleukin-13-induced goblet cell hyperplasia in human airway cells.

IL-13 is a T-helper class 2 cytokine that induces goblet cell hyperplasia and mucus production in airway epithelial cells. Because macrolide antibiotics are known to have immunomodulatory and mucoregulatory properties, the aim of this study was to examine the effect of clarithromycin on IL-13-induced goblet cell hyperplasia and mucin hypersecretion in normal human bronchial epithelial (NHBE) cells. NHBE cells were cultured to differentiation at an air-liquid interface with IL-13 plus clarithromycin or vehicle. Histochemical analysis was performed using H&E staining, periodic acid-Schiff (PAS) staining, and MUC5AC immunostaining. MUC5AC synthesis was assayed using RT-PCR and ELISA. Western blotting was used to evaluate signaling pathways. IL-13 significantly increased the number of PAS-positive, MUC5AC-positive goblet cells, and this was significantly attenuated by clarithromycin at concentrations greater than 8 µg/ml (P < 0.01). Clarithromycin also dose-dependently decreased MUC5AC mRNA expression induced by IL-13 (P < 0.001), and, at 24 µg/ml, clarithromycin significantly attenuated the amount of MUC5AC protein in cell supernatants (P < 0.01). Western blotting showed that clarithromycin affected IL-13 receptor janus kinase signal transducers, activators of transcription6 (STAT6), and epidermal growth factor receptor mitogen-activated protein kinase signaling and that inhibition of these pathways by clarithromycin decreased goblet cell hyperplasia via nuclear factor-κB inactivation. We conclude that clarithromycin inhibits goblet cell hyperplasia and may directly regulate mucus secretion by IL-13 in NHBE cells.

[Long term oxygen therapy and mechanical ventilation for patients with COPD].

Non-drug treatments such as long term oxygen therapy (LTOT) and non-invasive positive pressure ventilation (NPPV) are thought important for patients with chronic obstructive pulmonary disease (COPD). It is reported that LTOT can improve the prognosis of patients with COPD, particularly who have severe respiratory failure. NPPV attracted attention to avoid endotracheal intubation and high efficacy in patients with acute exacerbation of COPD. In chronic phase of COPD, NPPV may improve the quality of life in patients with hypercapnia, selected carefully.

Exogenous surfactant instillation attenuates inflammatory response to acid-induced lung injury in rat.

The present study was performed to investigate the role of exogenous surfactant on hydrochloric acid (HCL) - induced lung injury in rats. Six-week-old male Sprague-Dawley rats were anesthetized by intraperitoneal injection of pentobarbital sodium (40mg/kg) and HCL (0.1N, 2mL/kg) or normal saline (NS, 2mL/kg) was instilled into the trachea. Thirty minutes after HCL instillation, surfactant at a dose of 60mg (=2mL)/body or NS (2mL) was instilled into the rat lungs. Animals in another experimental group were also treated with the same dose of surfactant supplement 2hours after the first administration. Bronchoalveolar lavage fluid (BALF) was obtained 5hours after HCL instillation. In BALF, increases in total nuclear cell counts, neutrophil counts, optical density at 412nm as an indicator of pulmonary hemorrhage, neutrophil elastase activity, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) induced by HCL instillation were significantly attenuated by surfactant treatment. The wet-to-dry weight (W/D) ratio in the lung and partial oxygen tension (P(O2)) were also estimated; surfactant treatment significantly attenuated the W/D ratio and improved deteriorated P(O2) induced by HCL. Additional surfactant supplementation did not show further beneficial effects on HCL-induced lung injury compared with a single treatment. These results suggest that surfactant shows an anti-inflammatory effect on acid lung injury in rats but the beneficial effects may be dose limited.

Comparison of acid-induced inflammatory responses in the rat lung during high frequency oscillatory and conventional mechanical ventilation.

BACKGROUND: The present study was performed to compare the effects of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) on pulmonary inflammatory responses in a rat acid-induced lung injury model. METHODS: Anesthetized rats were instilled intratracheally with HCl (0.1 N, 2 mL/kg) and then randomly divided into three mechanical ventilation settings: HFOV (an oscillatory frequency of 15 Hz, mean airway pressure (MAP) of 9 cmH(2)O), CMV at tidal volume of 12 and 6 mL/kg for 5 h. RESULTS: After HCl instillation, HFOV significantly attenuated the increases in neutrophil infiltration and TNF-α concentration in bronchoalveolar lavage fluid compared with the CMV groups. During HFOV, there was an inhibition of an increase in TNF-α mRNA expression and a decrease in SP-A mRNA expression induced by acid instillation. CONCLUSION: This animal study demonstrates that HFOV is a suitable form of mechanical ventilation to prevent inflammatory responses in acid-induced lung injury.

Successful salvage chemotherapy with gemcitabine and vinorelbine in a malignant pleural mesothelioma patient previously treated with pemetrexed.

The role of second-line and salvage chemotherapy in malignant pleural mesothelioma treatment is not yet established. We report a case of relapsed malignant pleural mesothelioma in which the patient failed to respond to pemetrexed-based chemotherapy but was successfully treated with gemcitabine and vinorelbine. The patient underwent a left extrapleural pneumonectomy. Three years later she developed anterior chest wall and retroperitoneal masses. Histological findings revealed metastases from the malignant pleural mesothelioma. Although two cycles of carboplatin plus pemetrexed chemotherapy were administered, she had progressive disease. Then, 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine were administered every 2 weeks. The chemotherapy regimen was tolerated well, and the tumors were remarkably reduced. She was treated with 12 cycles of gemcitabine plus vinorelbine, and 8.5 months of progression-free survival was observed. Gemcitabine plus vinorelbine chemotherapy may be a candidate regimen for salvage chemotherapy against malignant pleural mesotheliomas.

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of pulmonary vascular status in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Lung uptake of iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) is used as an indicator of pulmonary endothelial function. Decreased lung uptake of ¹²³I-MIBG has been demonstrated in patients with COPD as compared with normal subjects. The present study was performed to examine the relationship between lung uptake of ¹²³I-MIBG and pulmonary artery pressure (Ppa) at rest and during exercise, in patients with COPD. METHODS: ¹²³I-MIBG scintigraphy was performed in 19 patients with COPD. Anterior planar images were acquired 15 min after the injection of ¹²³I-MIBG, and the total lung to upper mediastinum ratio (LMR) was calculated for both lungs. Right heart catheters were used to monitor Ppa continuously at rest and during exercise. Exercise was performed on an electrically braked bicycle ergometer at a constant workload of 25 W for 3 min. RESULTS: In COPD patients the LMR were not correlated with the pulmonary function parameters measured before exercise, including FEV1, PaO2, DL(CO), or Ppa at rest. However, the percentage increase in Ppa during exercise was significantly correlated with LMR. CONCLUSIONS: Evaluation of the kinetics of lung uptake of ¹²³I-MIBG may be a novel scintigraphic tool for the assessment of exercise-induced pulmonary hypertension in patients with COPD.

Clinical characteristics of combined pulmonary fibrosis and emphysema.

UNLABELLED: This study describes the clinical characteristics of patients with CPFE and compares these with patients with COPD. It should therefore be noteworthy that the prevalence of lung cancer might be high in CPFE patients. BACKGROUND AND OBJECTIVE: Patients with combined pulmonary fibrosis and emphysema (CPFE) are sometimes seen, and we speculate that these patients have some different clinical characteristics from COPD patients. This study clarifies the clinical characteristics of CPFE patients. METHODS: This was a retrospective study of 47 stable patients with concurrent emphysema and diffuse parenchymal lung disease with fibrosis, based on the findings of chest CT (CPFE patients). The clinical characteristics of CPFE patients were compared with those of emphysema-dominant COPD patients without parenchymal lung disease (COPD patients). RESULTS: Forty-six of the 47 CPFE patients were male. Paraseptal emphysema was particularly common in the CPFE group. Honeycombing, ground-glass opacities and reticular opacities were present in 75.6%, 62.2% and 84.4% of CPFE patients, respectively. Twenty-two of the 47 CPFE patients (46.8%) had lung cancer. Pulmonary function tests showed that the CPFE group had milder airflow limitation and lower diffusing capacity than the COPD group. Desaturation during 6-min walking test in CPFE patients tended to be more severe than in COPD patients, if the level of FEV1 or 6MWD was equal. CONCLUSIONS: CPFE patients had some different clinical characteristics in comparison with COPD patients and may also have a high prevalence of lung cancer.

A case of severe ARDS caused by novel swine-origin influenza (A/H1N1pdm) virus: a successful treatment with direct hemoperfusion with polymyxin B-immobilized fiber.

In 2009, a 35-year-old female with Down syndrome was admitted to our hospital because of severe pneumonia caused by an infection with the novel swine-origin influenza (A/H1N1pdm) virus (S-OIV). A chest X-ray on admission revealed bilateral infiltration shadows. Although mechanical ventilation was administered because of the development of ARDS, the hypoxemia continued to progressed. We observed evidence of alveolar hemorrhage on evaluation of the patient using bronchofiberscopy. The bacterial examination was negative. Despite intensive care, including respiratory management with high-frequency oscillatory ventilation (HFOV), the patient's hypoxemia and hypotension progressed. We concluded that a cytokine storm due to the influenza infection with SIRS caused shock status, resulting in septic shock. We subsequently treated the patient with direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP). The hypoxemia improved immediately. She was free from mechanical ventilation and discharged from the hospital by the 17th day of her hospitalization. PMX-DHP seems to improve hypoxemia in patients with severe ARDS who cannot maintain sufficient respiratory control under mechanical ventilation. This case is the first report about severe and life-threatening ARDS due to the novel influenza, in which PMX-DHP showed beneficial effects.

Identification of occult parechymal disease such as emphysema or airway disease using screening computed tomography.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a major public health problem. This study was performed to determine whether the low attenuation area (LAA) and visual score provided by low-dose computed tomography (CT) can be used to detect occult parenchymal disease, such as insidious COPD. METHODS: Each participant underwent low-dose CT scan and pulmonary function tests. The LAA% of the corresponding lung area was calculated. The cut-off level between the normal lung density area and LAA was defined as -960 HU, and the severity of emphysematous change (visual score) and LAA% were evaluated on three same chest CT slices obtained at full inspiration. RESULTS: Forty-eight of 2,247 individuals including 1058 non-smokers and 1189 smokers were diagnosed with COPD. Chest CT findings in individuals diagnosed with COPD showed centrilobular emphysema (50%), however, 17 of the subjects diagnosed with COPD had normal screening CT findings. Thirty-one subjects diagnosed with COPD showed a positive visual score, and 27 individuals with COPD showed LAA% of more than 30. Nine of 17 subjects with a negative visual score showed LAA% of more than 30. The visual score in smokers was significantly higher than that of non-smokers. The lung function in smokers was lower than that of non-smokers. Smokers also showed higher frequencies of chest CT abnormalities. CONCLUSION: Low-dose CT scans detected LAA and a positive visual score before COPD associated with an impaired lung function develops. Smokers with normal spirometry had a potential to develop an airflow obstruction accompanied with abnormal CT findings.

[Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension].

The Ministry of Health, Labour and Welfare (Japan) has approved research into primary pulmonary hypertension (PPH) and pulmonary hypertension due to chronic thromboembolic and/or embolic disease (CTE-PH) to examine their epidemiology, pathophysiology, and develop new therapeutic strategies. The Respiratory Failure Research Group, with grant support from the Ministry of Health, Labour and Welfare, changed the diagnostic names of PPH and CTE-PH. The Specific Diseases Control Division in the Health Service Bureau of the Ministry of Health, Labour and Welfare supported our proposal. One of the major purposes of The Respiratory Failure Research Group has been to maintain and, if possible, promote patient quality of life and prognosis in cases of intractable respiratory diseases. The name PPH has been changed to "pulmonary arterial hypertension (PAH)", and the name CTE-PH has been changed to "chronic thromboembolic pulmonary hypertension (CTEPH)", in keeping with recent worldwide research progress in this field. PAH should be subdivided into different pathophysiologic conditions, such as idiopathic and hereditary PAH, PAH associated with connective tissue diseases, portal hypertension, congenital heart disease, persistent pulmonary hypertension in newborn babies, pulmonary veno-occlusive disease etc. Different therapeutic strategies may be adopted for different subgroups. Pulmonary hypertension due to left heart disease, lung disease and/or hypoxia and CTEPH should be excluded from PAH. Continuous monitoring of PAH and CTEPH is required in patients with these conditions, even if the degree of pulmonary hypertension is improved by therapeutic intervention, because these diseases are incurable.

[A case of a pulmonary pleomorphic carcinoma with fever which responded well to chemotherapy].

BACKGROUND: Pulmonary pleomorphic carcinoma is a very rare pulmonary malignant tumor which has various clinical manifestations and a poor prognosis. CASE: A 74-year-old man presented with fever and weight loss of more than 10kg during 2 months from April 200X. Chest CT showed a nodule in the right upper lobe, and supraclavicular and mediastinal lymphadenopathy. Positron emission tomography (PET) comfirmed 18Ffluorodeoxyglucose accumulation in the sites. A left supraclavicular node biopsy demonstrated pulmonary pleomorphic carcinoma. The tumors responded well to gemcitabine plus docetaxel combination chemotherapy. This symptoms disappeared and the response continued for 1 year after 6 cycles of chemotherapy. CONCLUSION: We report a case of pulmonary pleomorphic carcinoma presenting with fever, which showed a marked response to chemotherapy.

[A case of primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome].

An 80-year-old man was admitted to our hospital with a 4.0 x 2.0 cm shadow accompanied by calcification, found on chest CT scans on a health check. The shadow was located in the left lower lobe (S10), and was attached to the pleura. A transbronchial biopsy did not yield a definitive diagnosis. A percutaneous needle biopsy yielded a diagnosis of leiomyosarcoma. A general examination did not show any metastatic lesions in other areas. However, the tumor grew rapidly, with pleural effusion, and therefore he was treated only by palliative therapy. He died from respiratory failure 90 days after onset. The primary site of the tumor was determined to be intrapulmonary area by radiographic and autopsy findings. We report a rare primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome.