Studies on the inflammatory changes in the airway mucosa of patients in the early stage of asthma and the necessity for inhaled glucocorticoids therapy for these patients.

从以下临床研究和动物实验的结果中提出了从哮喘早期开始吸入性糖皮质激素治疗的必要性。哮喘发病1年内哮喘患者的支气管黏膜炎症改变：与慢性哮喘患者一样，黏膜下层和上皮均可见嗜酸性粒细胞浸润。大多数嗜酸性粒细胞被激活。结论：1.虽然哮喘患者的基底膜厚度平均值明显低于哮喘病史2年以上的患者，但仍有患者基底膜明显增厚。吸入糖皮质激素对近期预后的影响始于哮喘发作后不久：大多数哮喘患者在哮喘发作后1年内开始吸入糖皮质激素治疗，哮喘症状在1个月内完全消失，对乙酰胆碱的反应性恢复正常。在这种情况下，…更多的患者经常不再去医院，这使得进行后续研究变得困难。相比之下，在接受缓释茶碱治疗并吸入β2-激动剂的哮喘患者中，哮喘控制并不完美，他们中的大多数人在病情恶化时来我们的门诊就诊。大剂量吸入糖皮质激素治疗对慢性哮喘患者基底膜增厚的影响：对5例接受大剂量吸入糖皮质激素治疗至少3年的慢性哮喘患者进行支气管活检，并比较两组标本的基底膜厚度。大剂量吸入糖皮质激素治疗后嗜酸性粒细胞浸润强度降低，但基底膜厚度无明显变化，提示吸入糖皮质激素治疗对已建立的气道重塑无效。白三烯受体拮抗剂对慢性哮喘豚鼠模型气道壁增厚的保护作用：用卵白蛋白(OA)致敏的豚鼠，随后在24周内每周雾化一次OA，显示明显的气道壁增厚，尤其是平滑肌层。用白三烯受体拮抗剂处理动物后，气道壁增厚被阻断，提示该药对气道重塑有抑制作用。较少

Necessity for starting inhaled glucocorticoids therapy from the early stage of asthma was suggested from the results of the following clinical studies and animal experiment.1. Inflammatory changes in the bronchial mucosa of asthma patients whose asthma onset had been within one year : Like patients with chronic asthma, eosinophil infiltration was observed both in the submucosa and epithelium. Most of eosinophils were activated. Although the mean value of basement membrane thickness was significantly less than that of patients whose asthma history was more than 2 years, there were patients with markedly thickened basement membrane.2. The effects of inhaled glucocorticoids started soon after the onset of asthma on the short-term prognosis : In most of asthmatics in whom inhaled glucocorticoids therapy was started within one year after the asthma onset, asthma symptoms completely disappeared within one month and bronchial responsiveness to acetylcholine was normalized. In such cases, the … More patients often discontinue to attend hospital, which made it difficult to perform follow up studies. In contrast, in asthmatics who were treated with sustained-release theophylline and inhaled beta2-agonist, asthma control was not perfect and most of them visited to our out clinic on exacerbations.3. Effects of high-dose inhaled glucocorticoids therapy on thickening of basement membrane in chronic asthma : Bronchial biopsies were done after receiving high-dose inhaled glucocorticoids therapy for at least 3 years in five patients with chronic asthma in whom bronchial biopsies had been performed before this therapy and the thickness of basement membrane in both specimens was compared. The intensity of eosinophil infiltration decreased after high-dose inhaled glucocorticoids therapy, but the thickness of basement membrane unchanged, suggesting that inhaled glucocorticoids therapy is not effective for established airway remodeling.4. Protective effect of leukotriene receptor antagonist on airway wall thickening in a guinea pig model of chronic asthma : Guinea pigs sensitized with ovalbumin (OA) and subsequently challenged with aerosolized OA once a week over 24 weeks showed marked airway wall thickening, in particular the smooth muscle layer. When animals were treated with leukotriene receptor antagonist, the airway wall thickening was blocked, suggesting the inhibitory effect of this drug on airway remodeling. Less