Bronchial subepithelial fibrosis and expression of matrix metalloproteinase-9 in asthmatic airway inflammation.

BACKGROUND: Bronchial asthma is characterized by airway structural changes, including mucosal inflammation and subepithelial collagen deposition. An imbalance between the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is thought to play a critical role in the synthesis or degradation of the extracellular matrix of the airway architecture. However, the relationship between subepithelial basement membrane thickness and these enzymes in asthma has not been determined. OBJECTIVE: We compared the thickness of collagen and tenascin deposition and the expression of MMP-9 and TIMP-1 in bronchial biopsy specimens from subjects with asthma and control subjects. METHODS: Bronchial biopsy specimens were obtained from 25 subjects with asthma and 10 healthy control subjects to estimate the extent of collagen and tenascin deposition in subepithelial reticular basement membrane by immunohistochemical staining. Using a computer-assisted image analysis system, we quantitated expression of both epithelial and submucosal MMP-9 and TIMP-1. The numbers of inflammatory cells were also determined. RESULTS: Subjects with asthma exhibited greater thickness of collagen III (P <.01), collagen V (P <.01), and tenascin (P <.01) deposition in reticular basement membrane than did control subjects. The proportions of epithelium and submucosa immunoreactive to MMP-9 and TIMP-1 were significantly higher in the subjects with asthma than in the control subjects (each P <.001). Submucosal expression of MMP-9 was significantly higher than that of TIMP-1 in subjects with asthma (P <.01). Significant correlations were found between the number of myofibroblasts and thicknesses of collagen III (rs = 0. 70, P <.001), collagen V (rs = 0.67, P <.001), and tenascin (rs = 0. 58, P <.01) in subjects with asthma. On the other hand, the number of eosinophils was correlated with degree of mucosal expression of MMP-9 (rs = 0.43, P <.05) and TIMP-1 (rs = 0.69, P <.001). In subjects with asthma, a significant inverse correlation was found between subepithelial fibrosis and FEV1 (type III collagen, rs = -0. 89, P <.001; type V collagen, rs = -0.90, P <.001; tenascin, rs = -0. 88, P <.001), and airway responsiveness (type III collagen, rs = -0. 59, P <.01; type V collagen, rs = -0.47, P <.05; tenascin, rs = -0. 48, P <.05). CONCLUSION: These findings suggest that collagen III, collagen V, and tenascin deposition in basement membrane in subjects with bronchial asthma are associated with increased expression of MMP-9, which may be produced by eosinophils, and that airway remodeling in subjects with asthma may be related to air-flow obstruction and airway hyperresponsiveness.

[The effect of azelastine on bronchial mucosa in bronchial asthma--suppression of cytokine mRNA].

Azelastine is an oral antiallergic drug. Although oral antiallergic drugs are classified as controllers because of the possession of anti-inflammatory effect, the mechanism of action has remained obscure. Thus the author investigated the effects of azelastine on inflammatory cells infiltrating into the bronchial mucosa and on the expression of cytokines in patients with atopic asthma. Biopsy specimens of the bronchial mucosa were bronchoscopically obtained before and after the administration of azelastine for 3 months. Inflammatory cells in the bronchial mucosa, including eosinophils, mast cells, macrophages, and T lymphocytes, were stained immunocytochemistry; expression of cytokine mRNA [Interleukin (IL)-4 and IL-5] was examined by the in situ hybridization method. The results obtained revealed that the number of eosinophils (p < 0.01), T lymphocytes (p < 0.01), and cells expressing mRNA of IL-4 (p < 0.05) or IL-5 (p < 0.01) significantly decreased after the administration of azelastine. These results suggest that azelastine inhibits the action on local infiltration of inflammatory cells and following proinflammatory cytokine production as one mechanism of bronchial asthma.

[A case of adenosquamous carcinoma with unknown origin and with superior vena cava syndrome as the first symptom].

This report is concerning a case of adenosquamous carcinoma having unknown origin and showing SVC syndrome as the first symptom. A 44 year-old man was admitted to our hospital because of facial edema at the beginning of April 1990. He was diagnosed as having a mediastinal tumor of the SVC syndrome type. Resection of the SVC tumor and part of the pericardium was performed on June 20, 1990. The operation had extraordinary findings. Lymph nodes adhering to tumor invaded the adjacent right side of the trachea and were situated in a rosette-like form. Furthermore, a part of the tumor stemmed into the lumen of the superior vena cava causing complete obstruction. The pathological diagnosis of the SVC tumor was adenosquamous carcinoma, however, no clinical examinations could identify its original matrix. Mediastinal tumors of unknown origin are reported as about 1% of all mediastinal tumors, and are responsible for 0.68% of all carcinomas in the mediastinum. This was one experience of a rare case of mediastinal tumor having unknown origin and showing SVC syndrome as the first symptom.