A possible role of galectin-9 in the pulmonary fibrosis of patients with interstitial pneumonia.

BACKGROUND: Galectin-9 (Gal-9) is a ß-galactoside-binding protein that induces biological reactions, such as cell activation, chemoattraction, and apoptosis. We evaluated the role of Gal-9 in the pathogenesis of interstitial pneumonia (IP). METHODS: Gal-9 levels in the bronchoalveolar lavage fluid (BALF) of patients with IP associated with collagen vascular disease (CVD-IP) and with idiopathic interstitial pneumonias (IIPs), including idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (idiopathic NSIP), were estimated by enzyme-linked immunosorbent assay. Gal-9 expression in the lungs of these patients was evaluated using immunohistochemistry. The effect of Gal-9 on the growth and apoptosis of human lung fibroblast cells was assessed in vitro. RESULTS: Gal-9 levels in the BALF were significantly higher in patients with CVD-IP than in patients with IIPs. Gal-9 levels significantly correlated with both the total cell count and the absolute number of lymphocytes in the BALF of patients with IIPs and CVD-IP. Strong reactivity with anti-Gal-9 antibody was observed in the cytoplasm of alveolar macrophages, lymphocytes, and type II pneumocytes in the lungs of patients with IP. Gal-9 expression in those cells was more remarkable in patients with CVD-IP than in patients with IPF and idiopathic NSIP. Gal-9 suppressed the growth of human lung fibroblast cells in a dose- dependent manner. Gal-9 induced apoptosis of human lung fibroblast cells in a dose-dependent manner. CONCLUSIONS: Our findings suggest that the expression level of Gal-9 in the lung is increased in patients with CVD-IP and that Gal-9 may have a protective role against pulmonary fibrosis of these patients.

[Bilateral pulmonary mucormycosis with diabetic ketoacidosis].

A 38 year-old woman admitted for bilateral infiltrates with a cavity and treated diabetic ketoacidosis and elevated inflammatory reaction in clinical examination was found in transbronchial lung biopsy specimens to have bilateral pulmonary mucormycosis. We controlled blood glucose with insulin and removed bilateral pulmonary lesions separately. Pulmonary mucormycosis with diabetic ketoacidosis is a rare but fatal fungal infection. Early diagnosis, intensive insulin therapy, and surgical resection may save patients with pulmonary mucormycosis even if lesions are bilateral.

[A case of Westermani Paragonimiasis with atypical change of CT findings].

A 47-year-old man presented with bloody sputum and a cavitary mass shadow was formed in his right middle lobe. Transbronchial lung biopsy revealed the presence of parasite eggs and eosinophil infiltration. Based on the positive reaction against Westermani Paragonimus by multiple dot ELISA, Westermani Paragonimiasis was diagnosed. The cavitary mass shadow disappeared after the treatment with Pragiquantel. This is a rare case of Westermani Paragonimiasis showing interesting changes of chest CT findings during its clinical course.

High concentrations of alpha-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome.

alpha-Defensins, antimicrobial peptides localized in neutrophils, participate in tissue damage through their cytotoxic effects in neutrophil-mediated pulmonary diseases. Neutrophils play an important role in the pathogenesis of acute respiratory distress syndrome (ARDS). We measured alpha-defensins levels in plasma and bronchoalveolar lavage fluid (BALF) of ARDS patients to assess the kinetics of alpha-defensins in ARDS. Plasma alpha-defensins levels were higher in ARDS patients than in control subjects, and BALF levels were also higher in ARDS patients than in control subjects. In ARDS, BALF alpha-defensins levels correlated with those of interleukin (IL)-8, and plasma alpha-defensins levels also correlated with Lung Injury Score. Peripheral neutrophil alpha-defensins contents were higher in ARDS than the control. IL-8 dose-dependently stimulated alpha-defensins release from cultured neutrophils and these levels were higher in ARDS than the control. Reverse-phase high performance liquid chromatography showed high plasma levels of pro-defensins, precursors of alpha-defensins from the bone marrow in ARDS, although alpha-defensins in peripheral and BALF neutrophils were mature type. In conclusion, high plasma alpha-defensins in ARDS patients result from the release of pro-defensins from bone marrow, rather than mature alpha-defensins from neutrophils that accumulate in the alveolar space. The alpha-defensins contents of peripheral neutrophils in ARDS are higher and easier to release than control.

A possible role of TARC in antigen-specific Th2-dominant responses in patients with Paragonimiasis westermani.

BACKGROUND: Paragonimiasis westermani (Pw), a common parasitic zoonosis in Asia, is typically associated with eosinophilia. Th2 cytokines seem to have an important role in the clinical manifestations of this disease. Thymus and activation-regulated chemokine (TARC) is a potential key regulator of Th2-mediated inflammation. The purpose of the present study was to evaluate the antigen-specific Th2-dominant responses in patients with Pw. METHODS: The concentrations of cytokines and chemokines in supernatants of peripheral blood mononuclear cell (PBMC) cultures with or without antigen stimulation were measured by enzyme-linked immunosorbent assay (ELISA). TARC levels in serum from Pw patients were also evaluated by ELISA. The number of Th2 cells expressing the CC-chemokine receptor 4 (CCR4) in the peripheral blood was evaluated by flow cytometry. RESULTS: Antigen-stimulation induced production of IL-5 and IL-13, but not IFN-gamma from PBMC cultures in patients with Pw. Pw patients had elevated serum TARC levels and a higher proportion of CCR4-expressing cells among CD4+ T cells in the peripheral blood. There were also higher levels of TARC, but not IP-10, in supernatants of antigen-stimulated PBMC culture compared to unstimulated PBMC culture in patients with Pw. CONCLUSION: Our findings clarify antigen-specific Th2-dominant responses in patients with Pw and suggest a possible role for TARC in Th2-dominant responses.

Elevated serum beta-defensins concentrations in patients with lung cancer.

BACKGROUND: Beta-defensins (HBDs) are expressed in lung epithelial cells and act as antimicrobial agents. Most lung cancers that originate from pulmonary epithelial cells may produce HBDs. MATERIALS AND METHODS: We measured serum HBD-1 and HBD-2 levels in healthy subjects (HS), patients with lung cancer and patients with pneumonia by radioimmunoassay. RESULTS: Serum HBD-1 levels were higher in patients with lung cancer than HS and patients with pneumonia. Serum HBD-2 levels were higher in patients with lung cancer than HS. When cut-off values for positive HBD-1 were set at mean + 2SD of HS, the sensitivity and specificity of HBD-1 for the whole group of patients with lung cancer were 76.4 and 94.0%, respectively, and the proportion of patients with HBD-1-positive lung cancer and clinical stage I was 69.2%. CONCLUSION: Serum HBDs levels were high in patients with lung cancer and the serum HBD-1 level could be used as an auxiliary diagnostic tool for lung cancer.

[Farmer's lung cases of a farmer and his son with high BAL fluid beta-D glucan levels].

A farmer and his son, who treated straw in a cowshed, were admitted to our hospital because of severe dyspnea during summer time. Their chest X-ray films revealed bilateral reticulonodular shadows in the middle to lower lung fields. Bronchoalveolar lavage (BAL) fluid analyses showed a high proportion of lymphocytes and an increased CD4/8 ratio. They were diagnosed with farmer's lung and treated with pulse therapy with methylprednisolone and tapering of steroid. Hypoxemia and interstitial shadow improved, though the farmer relapsed one day after getting home. Immune precipitation showed positive reactions against Aspergillus fumigatus, Aspergillus terreus and Nocardiopsis alba. Their beta D-glucan levels in BAL fluid were higher than those of healthy normal volunteers, whereas their beta D-glucan levels in serum were below the detection levels. Ventilation of the cowshed and wearing a mask should prevent recurrence of the disease.

[A case of eosinophilic pneumonia caused by visceral larva migrans due to Ascaris suum].

A 50-year-old male, living in the rural distinct of Kagoshima Prefecture complained of high fever and fatigue. Chest X-ray showed ground glass opacities in the right lung field. His symptoms and radiographic findings were gradually improved by intravenous or per os administraions of some antibiotics intravenously or per os. Following the chest computed tomography one month later demonstrated ground glass opacities in the right lung field. Examinations of peripheral blood showed increased IgE level but no eosinophila. Bronchoalveolar lavage fluid obtained from B4 showed high proportion of eosinophils. Because of the positive finding for Ascaris suum in the assay of multi dot-ELISA for parasite, he was diagnosed as Ascaris suum infection. The patient was successfully treated with Alvendazol. This is a rare case of Ascaris suum infection causing eosinophilic pneumonia.

Elevated levels of circulating adhesion molecules in patients with active pulmonary tuberculosis.

OBJECTIVE: Recent studies have indicated the importance of cell adhesion molecules in the pathogenesis of various inflammatory lung diseases. Our study was designed to determine whether five soluble adhesion molecules including soluble L-, E- and P-selectin (sL-, sE- and sP-selectin), intercellular adhesion molecule-1 (sICAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) in serum reflect the severity of active pulmonary tuberculosis (TB), and whether there is a distinct profile of these soluble molecules in this disease. METHODOLOGY: Using enzyme-linked immunosorbent assays, we measured the serum levels of these five soluble adhesion molecules in 31 patients with active TB and 11 healthy volunteers. RESULTS: Serum levels of sE-selectin, sP-selectin and sICAM-1, but not sL-selectin or sVCAM-1, were significantly higher in patients with active TB than in the control subjects (P < 0.001, each). Significant correlations were detected only between serum levels of sE-selectin and sP-selectin, sE-selectin and sICAM-1, and sP-selectin and sICAM-1. There was a significant correlation between the Gaffky scale result (a scale assessing the number of mycobacteria bacilli present) and all of the above adhesion molecules, except for sL-selectin. Serum levels of sE-selectin, sL-selectin and sICAM-1 also correlated with the CXR radiological score. Higher levels of sL-selectin and sICAM-1 were detected in the serum of patients with radiological cavity formation compared to those without. The ESR, C-reactive protein and circulating neutrophil counts all correlated significantly with sE-selectin, sP-selectin, sICAM-1 and sVCAM-1. CONCLUSION: The results suggest that there is a distinct profile of soluble adhesion molecules in active pulmonary TB and that sE-selectin, sP-selectin, and especially sICAM-1 appear to be the most sensitive clinical measures of disease severity.

[A case of negative pressure pulmonary hemorrhage (NPPH) due to upper airway obstruction induced by asphyxia].

A non-smoking 76-year-old woman was admitted to our hospital complaining of cough, bloodstained sputum and difficulty in breathing that had developed while she was eating a meal. The initial diagnosis was upper airway obstruction. Her past history revealed no major illness, except that she was under medication for the treatment of hypertension. On examination, chest radiography and computed tomography (CT) scans showed diffuse ground glass opacities in both lungs, and bronchoalveolar lavage studies further yielded findings compatible with pulmonary hemorrhage. The patient's symptoms and hypoxemia improved gradually without any specific treatment. Laboratory data showed no specific underlying cause, such as vasculitis or collagen vascular disease, for the pulmonary hemorrhage. We therefore reached a diagnosis of a negative pressure pulmonary hemorrhage (NPPH) caused by upper airway obstruction. Follow-up examinations after 7 months showed no abnormal findings in the chest radiography or arterial blood gas analysis. To our knowledge, this is the first case of negative pressure pulmonary hemorrhage in japan.