中重度哮喘患者气道内凝血因子的测定及吸入皮质激素对其的影响
2010/08/20
有证据显示哮喘患者气道内可以激活外源性凝血反应，血浆内和局部衍生因子均可能与此相关。假设在正常气道内的凝血物质是平衡的，在哮喘患者的诱导痰中则有纤维蛋白形成，并且经试验证实吸入皮质激素以及血浆渗出物可以影响这种平衡。
F J H Brims等人利用ELISA法和效能测定测量30名稳定期受试者（对照组10人，中度哮喘10人，重度哮喘10人）的高渗盐水诱导痰中的α2巨球蛋白和凝血因子含量。一部分患者于停止吸入皮质激素5天后再次进行诱导痰测定。研究发现停止吸入皮质激素后痰中纤溶酶原（IQR：13.92（6.12-16.17）VS4.82（2.14-13.32）ng/ml，95%CI：0.003-8.596，p=0.0499）和组织型纤溶酶原激活剂（t-PA） (IQR：5.57（3.57-14.35）VS 3.88（1.74-4.05）ng/ml，95%CI：0.828-9.972，p=0.0261）含量明显上升。在未经治疗的中度哮喘患者tPA水平远高于正常人群 （2.14 （0.0–2.53） ng/ml，p=0.0029）。与对照组相比，重度哮喘患者痰液中的α2巨球蛋白（p=0.0003）、凝血激酶（p=0.023）、纤溶酶原激活物抑制剂（p=0.0091）、凝血酶激活的纤维蛋白溶解抑制剂（p=0.0031）和纤维蛋白降解产物（p=0.0293）水平则更高，且有显著意义。
Brims等人的研究提出未经治疗的中度哮喘患者伴有纤维蛋白溶解增加，且可以通过吸入皮质激素纠正。重度哮喘患者应用大量皮质激素治疗会在气道内产生一个纤溶-抗纤溶的环境。该研究预测抑制纤维蛋白沉积有可能成为重度哮喘患者的治疗方法之一。
(于娜 沈阳中国医科大学附属第一医院呼吸内科 110001 摘译)
（Thorax 2009;64:1037-1043 /doi:10.1136/thx.2009.114439）
（Thorax 2009;64:1037-1043 /doi:10.1136/thx.2009.114439）
Coagulation factors in the airways in moderate and severe asthma and the effect of inhaled steroids
1. F J H Brims1,
2. A J Chauhan1,
Abstract
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. 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, was tested.
Methods: ELISA and activity assays were used to measure α2-macroglobulin (an index of plasma leakage) and coagulation factors in hypertonic saline-induced sputum of 30 stable subjects (10 controls, 10 with moderate asthma and 10 with severe asthma). 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 (inter quartile range (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). Subjects with severe asthma had significantly more α2-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 profibrinogenic, antifibrinolytic environment in the airways. This study suggests that inhibition of fibrin deposition in severe asthma may be a therapeutic approach.
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气道平滑肌重构在重度长期持续的哮喘患者中是一个动态过程
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哮喘气道平滑肌增厚与哮喘严重度相关，但与哮喘病程无关
