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The densitometric parameter of relative volume change calculated on paired inspiratory and expiratory MDCT using the threshold of -860 H in limited lung correlated closely with airway dysfunction in COPD regardless of the degree of emphysema.

Abstractfibroblasts, and that the thickness of the subepithelial collagen appears to be Background -Bronchial asthma is charlinked to an increase in bronchial reacterised by airway structural changes, insponsiveness and exacerbation of clinical cluding mucosal inflammatory infiltration manifestations. and subepithelial collagen deposition, that (Thorax 1998;53:21-27) may represent the morphological basis for the chronicity of the disease. The relationship between airway wall thickness Keywords: bronchial asthma, growth factors, fibroblast, remodelling of airway wall.and growth factors in asthma has not been elucidated. Methods -Bronchial biopsy specimens were obtained from 21 asthmatic patients Identification of the histopathological features and eight healthy subjects and the base-of bronchial asthma has been largely based ment membrane thickness was measured on the results of necropsy studies which have by light microscopy and electron micro-documented epithelial cell shedding, inflamscopy. At the same time the numbers of matory cell infiltrate with numerous eosinoeosinophils and fibroblasts were assessed phils, 1 2 and subepithelial collagen thickening. and the expression of transforming growth It has now become clear that this phenomenon factor 1 (TGF-1 ), platelet derived growth occurs in mild atopic asthma, even in patients factor (PDGF), and insulin like growth with a relatively short clinical history.3 In factor (IGF) I in the bronchial mucosa patients with asthma chronic inflammation dewas examined by immunostaining. The termines pathological changes in the airways relationship between the degree of thick-and causes marked remodelling of the structure ening of the subepithelial layer and both of the bronchi. 4 Bronchial biopsy specimens the clinical data and pulmonary function from asthmatic patients have indicated that the were also investigated.typical remodelling of the airways is caused by Results -The basement membrane of the thickening of the subepithelial layer.5 This view asthmatic patients was thicker than that has persisted, despite ultrastructural studies of the healthy controls (median 8.09 versus showing that the true epithelial basement mem-4.02 m). Electron microscopic examina-brane was normal and that the thickening was tion of the basement membrane revealed due to deposition of fibrillar collagen species, thickening of the subepithelial lamina re-leading to an increase in depth and density of ticularis; this thickening significantly cor-the lamina reticularis beneath the basement related with the number of fibroblasts in membrane.6 7 Further studies using antibodies the submucosa in the asthmatic subjects to different types of collagen have revealed an (r S =0.88) but not in the controls (r S =0.70). increase in the amount of interstitial collagen There was a significantly higher number of types I, III, and V and fibronectin in the eosinophils in the airways of the asthmatic thickened basal lamina of patients with subjects than in the healthy subjects asthma. histochemistry. Further...

Airway lumen measured at expiratory CT was more closely related to expiratory airflow measurements than was lumen measured at inspiratory CT. In addition, the changes of airway luminal area between inspiration and expiration were strongly related to airflow limitation.

Mucus overproduction is a clinical feature of asthma. Ca2+-activated Cl- channel 1 (CaCC1) has been identified as a protein that is expressed in intestinal epithelia and that plays an important role in fluid and electrolyte transport. Recently, its mouse counterpart, gob-5, was identified as a key molecule in the induction of murine asthma through mucus overproduction. To elucidate the relationship of CaCC1 to human asthma, we examined CaCC1 expression using real-time quantitative polymerase chain reaction analysis in bronchial tissues from patients with asthma and normal control subjects. The expression of CaCC1 was significantly upregulated in patients with bronchial asthma compared with control subjects. In situ hybridization and immunohistochemical analysis demonstrated that CaCC1 is located in the bronchial epithelium, especially in mucus-producing goblet cells. In vitro transfection of a CaCC1 expression vector into the human mucoepidermoid cell line, NCI-H292, increased mucus production and induced the MUC5AC gene. These results suggest that CaCC1 plays a direct role in mucus production and differentiation in goblet cells and may contribute to the pathogenesis of asthma through its mucus-inducing activity.