Search

Objectives: Obstructive sleep apnoea hypopnoea syndrome (OSAHS) is associated with increased morbidity and mortality due to cardiovascular disease. In order to examine the association between OSAHS and cardiovascular disease, this study measured hypoxia-inducible and atherosclerosis-associated molecules in the peripheral blood. Methods: In this study peripheral blood was obtained early in the morning from 60 consecutive male patients with OSAHS (AHI ≥10 events/h) and 30 male control subjects without OSAHS (AHI

Simplified sleep polysomnography was performed in 207 adult men to examine the relationship between the frequency of sleep-disordered breathing (SDB) and lifestyle-related illness.Each subject was checked for SDB using a simplified sleep polysomnograph (Auto-Set Portable; Teijin Limited, Tokyo, Japan). Apnea and hypopnea were detected with a nasal cannula type airflow sensor. Hypoxemia was checked with a percutaneous oxygen saturation (SpO2) monitor. We analyzed the relationships between SDB and body mass index (BMI) and hypertension, hyperlipidemia, liver dysfunction, fatty liver, and abnormal glucose metabolism.Fifty-nine subjects (29%) showed SDB with apnea hypopnea index (AHI) over 15 times/h. The frequency of obesity (BMIor = 25), hypertension, hypercholesterolemia, fasting blood glucose level, and HbA1c were significantly higher in patients with SDB than in normal individuals (AHI5 times/h). The frequencies of hypertension, hyperlipidemia, and abnormal glucose metabolism were compared between the obesity-free normal AHI group and the SDB group, and only that of hypertension was significantly different between the two groups.The present study revealed a high frequency of SDB among Japanese individuals. The results also suggest that as SDB becomes severe, it becomes more closely linked to the onset of lifestyle-related illnesses, such as hypertension, hypercholesterolemia and abnormal glucose metabolism.

We present a case of primary malignant lymphoma arising from the posterior mediastinum. A 63-year-old woman was admitted to our hospital for further examination of her chest radiographic findings. She was asymptomatic. Chest computed tomography (CT) and magnetic resonance imaging (MRI) showed a posterior mediastinal mass in the right thoracic paravertebral region. A percutaneous needle biopsy was performed under CT. The histological findings with immunochemical staining revealed a B cell type of diffuse malignant lymphoma. 67Ga scintigraphy revealed accumulation in this area, suggesting the posterior mediastinum as the origin of the disease. Reports of primary malignant lymphoma in the posterior mediastinum are extremely rare. The radiographic characteristics are discussed.

Methotrexate-induced pneumonitis has been reported as an infrequent but potentially serious complication of therapy in a variety of malignant and benign conditions. Because inflammatory cell infiltration is concerned with the development of methotrexate-induced pneumoinitis, and because airway epithelial cells participate in the orchestration of lung inflammation, the authors determined whether methotrexate might stimulate airway epithelial cells (A549 cells) to release neutrophil, monocyte, and eosinophil chemotactic activities (NCA, MCA, and ECA). A549 cells released NCA, MCA, and ECA in a dose- and time-dependent manner in response to methotrexate. Partial characterization revealed the heterogeneity of NCA, MCA, and ECA. The release of chemotactic activity was blocked by lipoxygenase inhibitors and cycloheximide. NCA was inhibited by leukotriene (LT) B(4) receptor antagonist, and anti-interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) antibodies. MCA was attenuated by LTB(4) receptor antagonist, and anti-monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage CSF (GM-CSF) antibodies. ECA was attenuated by LTB(4) receptor antagonist, and anti-IL-8 and GM-CSF antibodies. The release of IL-8, G-CSF, MCP-1, GM-CSF, and LTB(4) from A549 cells significantly increased in response to methotrexate. The mRNA expression of IL-8 and MCP-1 was augmented by methotrexate stimulation. These data suggest that type II epithelial cells may modulate inflammatory cell recruitment into the lung by releasing NCA, MCA, and ECA in response to methotrexate.

Cyclophosphamide is an alkylating antineoplastic agent used in several conditions. However, little is known about the mechanism of its pulmonary toxicity. In the present study, we determined that human lung fibroblasts release activity for neutrophils and monocytes in response to cyclophosphamide in a dose- and time-dependent manner. Checkerboard analysis revealed that both neutrophil and monocyte activities were chemotactic. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular-sieve column chromatography revealed that both neutrophil (NCA) and monocyte (MCA) chemotactic activities had multiple peaks. NCA was inhibited by a leukotriene B4receptor antagonist and anti-interleukin-8 and anti-granulocyte colony-stimulating factor antibodies. MCA was attenuated by a leukotriene B4receptor antagonist and anti-monocyte chemoattractant protein-1 and anti-granulocyte-macrophage colony-stimulating factor antibodies. The concentrations of interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor significantly increased in response to cyclophosphamide. These data suggest that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing NCA and MCA in response to cyclophosphamide.

To predict the natural history of pulmonary Mycobacterium avium-intracellulare (MAI) infection with nodular bronchiectasis, we retrospectively evaluated clinical manifestations, laboratory data, and bronchoalveolar lavage fluid (BALF) findings in 57 patients. The patients received follow-up chest computed tomographic scans and testing for sputum bacteriology between intervals of at least 12 mo. They were divided into two groups after observation for 28 +/- 13 mo: deteriorated (n = 34) and not-deteriorated (n = 23). There were no patients with spontaneous improvement. At the start of observation, the mean age was greater in the deteriorated group (69 +/- 9 yr) than in the not-deteriorated group (57 +/- 9 yr). The mean body-mass index was lower in the deteriorated group (19.2 +/- 3.1 kg/m(2)) than in the not-deteriorated group (21.5 +/- 1.5 kg/m(2)). C-reactive protein, erythrocyte sedimentation rate, and carbohydrate antigen 19-9 were significantly elevated in the deteriorated group. The BALF findings of the deteriorated group showed that the neutrophil cell counts were significantly increased. Thirty-four of 57 patients with pulmonary MAI infection with nodular bronchiectasis had progressive clinical and/or radiographic disease. The older and thinner patients tended to become worse. Neutrophil-related inflammation associated with a decrease in CD4+ lymphocyte might reflect the progression of pulmonary MAI infection with nodular bronchiectasis.

We determined whether human lung fibroblasts (HLFs) might release mediators that are responsible for monocyte chemokinetic activity (MCA) constitutively. HLF supernatant fluids showed MCA in a time-dependent manner ( P 4(LTB4)-receptor antagonist attenuated the total MCA and the lowest molecular weight peak of MCA. The concentrations of LTB4were 153.4 ± 12.4 (24 h) and 212 ± 16.6 (72 h) pg/ml. These findings suggest that HLFs may modulate the recruitment of monocytes into the lung by releasing MCP-1, GM-CSF, TGF-β, and LTB4constitutively.

Optimal chemotherapeutic regimen in thymic carcinoma remains uncertain and the efficacy of second line chemotherapy has not been established either.We retrospectively evaluated the efficacy of an irinotecan plus cisplatin or carboplatin (IP) regimen as a salvage treatment for patients with unresectable thymic carcinoma that progressed after cisplatin, doxorubicin, vincristine and cyclophosphamide (ADOC) chemotherapy. Seven patients with histologically confirmed thymic carcinoma that was resistant to or who had relapsed after initial chemotherapy with ADOC were treated with IP. The treatment consisted of irinotecan (CPT-11, 60 mg/m2, days 1, 8 and 15) and cisplatin (80 mg/m2, day 1) or carboplatin (AUC 4) intravenously every 4 weeks, for at least 2 cycles.Two patients achieved partial responses. Although another two patients showed a significant reduction of the primary thoracic lesion, the appearance of a new lesion was found in one and a metastatic lesion was unchanged in the other. Neutropenia over grade 3 was observed in all patients but none of the patients developed serious infections. There were no severe non-hematological toxicities, including diarrhea.We conclude that salvage chemotherapy may be useful in certain patients with thymic carcinoma and irinotecan may be a novel and alternative agent for relapsed thymic carcinoma.

Diagnoses of infectious tuberculosis (TB) patients were followed by thorough contact investigation on the basis of our hospital's Infectious Disease Manual ever since an infection of an inpatient with extended hospital stay was confirmed by a positive acid-fast sputum smear in October 1998. In September 2000, a nurse was found to have pulmonary TB and another was given a diagnosis of right tuberculous pleuritis the following November. Contact investigations were expedited among all hospital staff, families of the infected nurses, and all suspected inpatients. Five were diagnosed as TB, 8 were given chemoprophylaxis and 8 others required observation. The result verified a TB outbreak within the hospital, and management of TB infection control was re-enforced subsequently. We concluded that immediate contact investigation promoted successful early diagnosis, and reacknowledged the significance of the health supervision of all staff, operations including the environment and equipment control of the institution, and frequent contact and integration with the administration of the public health center. This experience enabled a useful revision of the disease manual for the future.

The role of systemic chemotherapy and optimal regimen in thymic carcinoma remains uncertain. We evaluated the clinical responsiveness of ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) chemotherapy for advanced thymic carcinoma that have distant metastatic or unresectable lesions. From 1996 to 2000, we treated eight cases of thymic carcinoma. According to the classification by Masaoka et al., the clinical stage in one case was IVa, whereas the others were IVb. Histologic subtypes were as follows: four cases were squamous cell carcinoma, two cases were undifferentiated, and two were small-cell carcinoma. All patients received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously on day 1, 0.6 mg/m2 of vincristine intravenously on day 3, and 700 mg/m2 of cyclophosphamide intravenously on day 4, ADOC regimen, respectively, at 3- to 4-week intervals. Six patients obtained a partial response after ADOC chemotherapy and the overall clinical response rate was 75%. There were no life-threatening side effects noted. Cisplatin plus VP-16 chemotherapy (PVP) was performed in three cases before the ADOC regimen, but PVP chemotherapy did not show beneficial effects in two patients. Median survival time was 19 months. ADOC chemotherapy appears to have significant activity against thymic carcinoma.

Objectives: Lyophyllum aggregatum (LA) is called Shimeji in Japanese and is eaten commonly as a mushroom. Shimeji mushrooms are cultivated in an indoor environment all year round. This study aimed to clarify the clinical features of hypersensitivity pneumonitis (HP) induced by LA. Patients and setting: Ten patients showed mild respiratory symptoms including dry cough, sputum, and low-grade fever. We tried to characterize the clinical features and the findings using chest high-resolution CT (HRCT), pulmonary function tests (PFTs), and BAL fluid (BALF) tests in patients with HP induced by LA. HP was diagnosed from clinical features, HRCT findings, BALF findings, lung histology, and lymphocyte stimulation tests (LSTs) for LA. Results: Laboratory findings showed mean ( SD) elevated levels of C-reactive protein (0.78 1.3 mg/dL), erythrocyte sedimentation rate (48 23 mm/h), and -globulin (26.9 7.6%). PFTs revealed a slight decrease in the percentage diffusing capacity of the lung for carbon monoxide, possibly due to the presence of epithelial granulomas in the alveoli. Although 4 of 10 patients showed normal findings on the chest radiograph (CXR), chest HRCT findings of all patients showed centrilobular small nodules and diffuse ground-glass opacities. The BALF testing revealed an increase in total cell counts, showing predominantly activated T lymphocytes. The CD4/CD8 cell ratio was significantly decreased (0.5 0.3). The results of the LSTs were positive in seven of seven cases. Conclusions: Since patients with HP induced by LA typically have mild respiratory symptoms and sometimes normal CXR findings, their conditions might remain undiagnosed. However, the chest HRCT images showed the typical subacute phase of HP. (CHEST 2001; 120:1085–1093)

Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner ( P < 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) B4-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an LTB4-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung.

Theophylline inhibits eosinophilic infiltration into the bronchial wall. It is unknown whether this is mediated by a cyclic adenosine monophosphate (c-AMP)-dependent reduction in eosinophil chemotactic activity (ECA) from bronchial epithelial cells (BEC). Therefore the effect of a beta2-agonist, procaterol and theophylline on the release of ECA from a BEC line, BEAS-2B was evaluated in response to interleukin (IL)-1beta and tumour necrosis factor-alpha (TNF-alpha). ECA was assessed using a blind-well chemotactic chamber, and the release and gene expression of cytokines were evaluated by means of enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. IL-1beta and TNF-alpha stimulated the release of ECA from BEAS-2B cells in a dose- and time-dependent manner. Procaterol and theophylline directly inhibited eosinophil migration to IL-1beta and TNF-alpha-conditioned medium. The pretreatment of BEAS-2B cells with the same concentrations of procaterol inhibited the release of ECA in a dose-dependent fashion. Anti-IL-8, anti-regulated on activation, normal T-cell expressed and secreted (RANTES), and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited ECA. Procaterol inhibited the release of RANTES, GM-CSF and IL-8 in a dose-dependent fashion. The effect of theophylline was less potent. Procaterol augmented cAMP levels in BEAS-2B cells in a time- and dose-dependent manner. The expression of IL-8, RANTES, and GM-CSF messenger ribonucleic acid was not inhibited by procaterol and theophylline. These data indicate that procaterol and theophylline may directly inhibit eosinophil migration and that procaterol may further inhibit the release of eosinophil chemotactic activity from BEAS-2B cells via a cyclic adenosine monophosphate-dependent mechanism. This warrants further studies on the involvement of bronchial epithelial cells in the anti-inflammatory effects of procaterol and theophylline in patients with asthma.

Although bleomycin, an antineoplastic drug, is used in the treatment of a variety of tumors, the mechanisms of bleomycin-induced lung injury and fibrosis are not fully elucidated. We postulated that bleomycin might stimulate A549 cells, a type II pneumocyte cell line, to release neutrophil and monocyte chemotactic activities (NCA and MCA, respectively). To test this hypothesis, A549 cell supernatant fluids were harvested and evaluated for NCA and MCA. A549 cell supernatant fluids showed NCA and MCA in response to bleomycin in a dose- and time-dependent manner ( P < 0.05). Checkerboard analysis revealed that both NCA and MCA were predominantly chemotactic. Partial characterization of the released NCA and MCA showed that the activities were partially heat labile, trypsin digested, and predominantly ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of chemotactic activities significantly. Molecular-sieve column chromatography revealed that the released activities were heterogeneous. However, low-molecular-weight activity was prominent. Leukotriene B4-receptor antagonist, anti-interleukin-8, anti-granulocyte colony-stimulating factor, and anti-monocyte chemoattractant protein-1 antibodies attenuated the chemotactic activities. Immunoreactive leukotriene B4receptor, interleukin-8, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1 significantly increased in supernatant fluids in response to bleomycin. These data demonstrate that bleomycin stimulates type II epithelial cells to release chemotactic activities and plays a role in inflammatory cell recruitment into the lung.

We determined whether human lung fibroblasts might release chemotactic activity for neutrophils (NCA) and monocytes (MCA) in response to bleomycin. The human lung fibroblasts supernatant fluids were evaluated for chemotactic activity by a blind well chamber technique. Human lung fibroblasts released NCA and MCA in a dose- and time-dependent manner in response to bleomycin. Checkerboard analysis of supernatant fluids revealed that both NCA and MCA were chemotactic. Partial characterization revealed that NCA was partly heat labile, trypsin sensitive, and predominantly ethyl acetate extractable. In contrast, MCA was partly trypsin sensitive and ethyl acetate extractable. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular sieve column chromatography revealed that both NCA and MCA had multiple chemotactic peaks. NCA was inhibited by leukotriene B4 receptor antagonist and anti-IL-8 and G-CSF Abs. MCA was attenuated by leukotriene B4 receptor antagonist, and monocyte chemoattractant protein-1, GM-CSF, and TGF-β Abs. Leukotriene B4 receptor antagonist and these Abs inhibited the corresponding m.w. chemotactic activity separated by column chromatography. The concentrations of IL-8, G-CSF, monocyte chemoattractant protein-1, GM-CSF, and TGF-β in the supernatant fluids significantly increased in response to bleomycin. These data suggest that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing NCA and MCA in response to bleomycin.

Inflammatory cells accumulate within the lungs of cigarette smokers. Current concepts suggest that these cells can induce protease-antiprotease and/or oxidant-antioxidant imbalance(s), which may damage the normal lung alveolar and interstitial structures. Because type II pneumocytes line the alveolar space, and because the inflammatory cells migrate and reside at the alveolus, we postulated that the type II pneumocytes might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, A549 cells were cultured and the supernatant fluids were evaluated for the neutrophil and monocyte chemotactic activity (NCA and MCA) by a blind-well chamber technique. A549 cells released NCA and MCA in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was chemotactic. Partial characterization of NCA and MCA revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of NCA and MCA. Molecular sieve column chromatography showed multiple peaks for both NCA and MCA. NCA was inhibited by anti-human-interleukin (IL)-8 antibody, granulocyte colony-stimulating factor (G-CSF) antibody, or leukotriene (LT)B4 receptor antagonist. Monocyte chemoattractant protein (MCP)-1 antibody or LTB4 receptor antagonist inhibited MCA. Immunoreactive IL-8, G-CSF, MCP-1, and LTB4 significantly increased in the supernatant fluids in response to smoke extract. These data suggest that the type II pneumocytes may release NCA and MCA and modulate the inflammatory cell recruitment into the lung.

We evaluated the potential of A549 cells, an alveolar type II epithelial cell line, to release granulocyte colony-stimulating factor (G-CSF), in addition to interleukin (IL)-8 and leukotriene B4, as neutrophil chemotactic activity (NCA). Human recombinant IL-1β stimulated A549 cells to release NCA in a time- and dose-dependent fashion. The released NCA was blocked by mouse anti-human G-CSF polyclonal antibody. Molecular-sieve column chromatography revealed that IL-1β induced the release of a 19- to 20-kDa chemotactic mass that was inhibited by anti-human G-CSF antibody. IL-1β stimulated the release of G-CSF in a dose-dependent fashion, but the time-dependent profile of G-CSF showed that the concentration of G-CSF declined after 48 h. Tumor necrosis factor (TNF)-α, Escherichia coli lipopolysaccharide (LPS), and bradykinin (BK) stimulated A549 cells to release NCA that was inhibited by anti-G-CSF antibody. The release of G-CSF in response to TNF-α, LPS, and BK was significantly increased. The similar concentrations of human recombinant G-CSF (10–1,000 pg/ml) as in the supernatant fluid induced neutrophil chemotaxis. G-CSF mRNA was expressed time and dose dependently at 4 h and declined after 4 h in response to IL-1β as evaluated by RT-PCR. The expression of G-CSF mRNA was also observed by TNF-α, LPS, and BK stimulation. These data suggest that type II alveolar epithelial cells may produce G-CSF as NCA and may participate in the regulation of leukocyte extravasation.

To clarify the structure and function of the airways in Mycobacterium avium-intracellulare (MAI) infection, we performed pulmonary function tests and high-resolution computed tomography (HRCT) of the thorax in female patients 61 +/- 9 yr of age (n = 12) with pulmonary MAI infection without predisposing lung disease and compared their data with those of normal female volunteers 54 +/- 8 yr of age (n = 9). We calculated the E/I ratio, i.e., the average ratio of HRCT number at full expiration to that at full inspiration, as an index for the evaluation of air trapping distal to the small airways. Patients showed significant increases in residual volume and slope of phase III (DeltaN2) of the single-breath nitrogen test, and significant decreases in flow at 50 and 25% of FVC, suggesting hyperinflation and obstruction of the small airways. HRCT of patients revealed the small nodules and ectasis of bronchioles and small bronchi located mainly in segments (S) S2, S3, S4, and S5. The E/I ratio was significantly elevated in patients, and especially higher in the upper lung field than in the lower lung field, suggesting air trapping distal to the small airways. The difference of E/I ratio between the upper and lower field is probably related to the segmental distribution of CT abnormalities. These findings suggest that MAI infection can lead to air trapping distal to the small airways.