title: Inhaled corticosteroid reduced lamina reticularis of the basement membrane by modulation of insulin-like growth factor (IGF)-I expression in bronchial asthma.
abstract: BACKGROUND
  Pathological studies of bronchial biopsy specimens have confirmed the apparent thickening of lamina reticularis of the epithelial basement membrane. Corticosteroids have proven to be most effective in modifying airway inflammation. However, there is not much data on the effects of corticosteroid-treatment on the basement membrane.
  
  
  OBJECTIVE
  To investigate the effects of inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane and cellular infiltration into the bronchial mucosa, and the expression of growth factors in patients with asthma.
  
  
  METHODS
  We studied bronchial biopsies from 24 asthmatic patients before and after treatment with inhaled BDP, 400 microg twice a day or placebo, for 6 months in a double-blind manner. Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. The thickness of the basement membrane was determined by electron microscopy. Inflammatory cells and the expression of growth factors were examined by immunohistochemistry in endobronchial biopsy specimens.
  
  
  RESULTS
  After 6 months of treatment, we observed a significant improvement of asthma symptoms (P<0.01), PEF (P<0.01), diurnal variation of PEF (P<0.05), and airway responsiveness (P< 0.05) in the BDP group compared with the placebo group. This was accompanied by a significant decrease in the thickness of the lamina reticularis (P < 0.001), and in the number of activated eosinophils (P<0.01), T-lymphocytes (P<0.01), and fibroblasts (P < 0.05) in BDP-treated patients. There was also a reduction in the expression of insulin-like growth factor (IGF)-I (P < 0.01). Significant correlation was found between the IGF-I expression and collagen thickening (rs = 0.34, P<0.01), and the number of fibroblasts (rs = 0.45, P < 0.01).
  
  
  CONCLUSIONS
  These results suggest that corticosteroid treatment in asthma can reduce the lamina reticular thickness by modulation of IGF-I expression with consequent inhibition of the airway infiltration by inflammatory cells, and therefore may help to prevent remodelling of the airways.
authors.affiliation: Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hoshino
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: J J
authors.initials: JJ
authors.lastname: Sim
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashiro
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Hosaka
authors.forename: S
authors.initials: S
authors.lastname: Isogai
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001485:Basement Membrane / Q000473:pathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D001999:Bronchoscopy; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008854:Microscopy, Electron; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D010366:Peak Expiratory Flow Rate
chemical_list: D018927:Anti-Asthmatic Agents; D007334:Insulin-Like Growth Factor I; D001507:Beclomethasone