中度和重度哮喘中气道中的凝血因子以及吸入性糖皮质激素的作用
2009/10/15
背景：有证据表明，哮喘患者气道中的外源性凝血通路活化可能与血浆和局部衍生的某些因子相关。我们认为通过痰诱导取样的健康气道中正常的凝血平衡有助于哮喘患者气道纤维蛋白的形成，而吸入糖皮质激素（ICS）及血浆渗出能影响该平衡。
方法：采用ELISA和活性分析检测30名受试对象（10例名对照，10例轻度哮喘患者，10例重症哮喘患者）高渗盐水诱导的痰液中α-2-巨球蛋白（一种血浆渗漏指数）和凝血因子。此外，中度哮喘患者停止使用ICS，并在停止糖皮质激素5天后进行痰诱导试验。
结果：停止使用ICS显著增加痰液纤溶酶原（中位数 (IQR): 13.92 (6.12-16.17) vs. 4.82 (2.14-13.32) ng/ml; 95% CI： 0.003-8.596, P=0.0499）和组织纤溶酶原活化物（tPA; 5.57 (3.57-14.35) vs. 3.88 (1.74-4.05) ng/ml; 95%CI：0.828-9.972, P=0.0261）。未治疗的中度哮喘患者的tPA水平显著高于正常值（2.14 (0.0-2.53) ng/ml）（P=0.0029）。与对照组相比，严重哮喘患者痰液α-2-巨球蛋白（P=0.0003）、组织因子（P=0.023）、纤溶酶原活化物抑制剂（P=0.0091）、凝血酶激活的纤溶抑制物（P=0.0031）及纤维蛋白降解产物（P=0.0293）显著增加。
结论：未治疗的中度哮喘与纤维蛋白溶解增加相关，后者能被ICS所纠正。严重哮喘和高剂量糖皮质糖皮质激素治疗与气道内促纤维蛋白原和抗纤维蛋白溶解环境相关。我们研究表明，抑制严重哮喘患者气道纤维蛋白沉积可能成为哮喘的治疗措施之一。
（林江涛 审校）
Brims FJ, et al. Thorax. 2009 Aug 23. [Epub ahead of print]
Coagulation factors in the airways in moderate and severe asthma and the effect of inhaled steroids.
Brims FJ, Chauhan AJ, Higgins BR Mr, Shute JK.
Portsmouth Hospitals NHS Trust, United Kingdom.
BACKGROUND: There is evidence of activation of the extrinsic coagulation cascade in the asthmatic airway and both plasma and locally-derived factors may be involved. We tested the hypothesis that the normal haemostatic balance of healthy airways sampled by sputum induction favours fibrin formation in asthmatic airways, and that inhaled corticosteroids (ICS) and plasma exudation influence this balance.
METHODS: ELISA and activity assays were used to measure alpha-2-macroglobulin (an index of plasma leakage) and coagulation factors in hypertonic saline-induced sputum of 30 stable subjects (10 controls, 10 moderate and 10 severe asthmatics). Additionally, the moderate cohort were weaned off their ICS, followed by further sputum induction 5 days after cessation of steroids.
RESULTS: ICS wean induced a significant rise in plasminogen (median (IQR): 13.92 (6.12-16.17) vs. 4.82 (2.14-13.32) ng/ml; 95% CI 0.003 to 8.596, p=0.0499) and tissue-plasminogen activator (tPA; 5.57 (3.57-14.35) vs. 3.88 (1.74-4.05) ng/ml; 95% CI 0.828 to 9.972, p=0.0261) levels in sputum, such that tPA in untreated moderate asthma was significantly (p=0.0029) higher than normal (2.14 (0.0-2.53) ng/ml). Severe asthmatics had significantly more alpha-2 macroglobulin (p=0.0003), tissue factor (p=0.023), plasminogen activator inhibitor (p=0.0091) thrombin activatable fibrinolysis inhibitor (p=0.0031) and fibrin degradation products (p=0.0293) in their sputum than control subjects.
CONCLUSION: Untreated moderate asthma is associated with increased fibrinolysis that is corrected by ICS. Severe asthma and high dose corticosteroid therapy is associated with a pro-fibrinogenic, anti-fibrinolytic environment in the airways. Our study suggests that inhibition of fibrin deposition in severe asthma may be a therapeutic approach.
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吸入性糖皮质激素加用妥洛特罗贴剂（β2受体激动剂）对哮喘的治疗效果
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卵清蛋白致敏的豚鼠中吸入孟鲁司特抑制半胱氨酰白三烯诱导的支气管收缩：治疗哮喘的一种潜在新药
