Hoshino M, Nakamura Y, Sim J J, Yamashiro Y, Uchida K, Hosaka K, Isogai S
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Clin Exp Allergy. 1998 May;28(5):568-77. doi: 10.1046/j.1365-2222.1998.00277.x.
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.
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.
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.
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).
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.
支气管活检标本的病理学研究已证实上皮基底膜网状层明显增厚。皮质类固醇已被证明在改善气道炎症方面最为有效。然而,关于皮质类固醇治疗对基底膜影响的数据并不多。
研究吸入丙酸倍氯米松(BDP)对哮喘患者基底膜厚度、支气管黏膜细胞浸润以及生长因子表达的影响。
我们以双盲方式研究了24例哮喘患者在吸入BDP(每日两次,每次400微克)或安慰剂治疗6个月前后的支气管活检情况。每位受试者记录每日哮喘症状和呼气峰流速(PEF)。在治疗前后测量肺功能和支气管对乙酰甲胆碱的反应性。通过电子显微镜确定基底膜的厚度。在内支气管活检标本中通过免疫组织化学检查炎症细胞和生长因子的表达。
治疗6个月后,与安慰剂组相比,BDP组患者的哮喘症状(P<0.01)、PEF(P<0.01)、PEF日变化(P<0.05)和气道反应性(P<0.05)有显著改善。这伴随着BDP治疗患者的网状层厚度显著降低(P<0.001),以及活化嗜酸性粒细胞数量(P<0.01)、T淋巴细胞数量(P<0.01)和成纤维细胞数量(P<0.05)的减少。胰岛素样生长因子(IGF)-I的表达也有所降低(P<0.01)。发现IGF-I表达与胶原增厚(rs = 0.34,P<0.01)和成纤维细胞数量(rs = 0.45,P<0.01)之间存在显著相关性。
这些结果表明,哮喘患者使用皮质类固醇治疗可通过调节IGF-I表达来减少网状层厚度,从而抑制炎症细胞对气道的浸润,因此可能有助于预防气道重塑。