Pedersen B, Dahl R, Karlström R, Peterson C G, Venge P
Department of Lung Medicine, University Hospital, Arhus, Denmark.
Am J Respir Crit Care Med. 1996 May;153(5):1519-29. doi: 10.1164/ajrccm.153.5.8630596.
The object of this investigation was to study the long-term effects of antiasthma treatment on blood markers of inflammation and lung function in adult asthmatic subjects. For this purpose 85 allergic and nonallergic asthmatic subjects were randomized into three groups, which were given high-dose (1,600 micrograms/d) inhaled budesonide, low-dose (400 micrograms/d) inhaled budesonide, and oral theophylline (600 mg/d), respectively, and were followed for 11 mo with testing of lung function and blood sampling for the assay in serum of eosinophil cationic protein (ECP), eosinophil protein x/eosinophil derived neurotoxin (EPX/EDN) as eosinophil markers, and myeloperoxidase (MPO) and lactoferrin (LF) as neutrophil markers. Lung functions (FEV1% predicted, and histamine PC20) and the eosinophil markers ECP and EPX/EDN were improved and reduced, respectively, by budesonide in a dose-dependent and temporally parallel fashion. Theophylline did not alter lung functions but reduced ECP and EPX/EDN after prolonged treatment. The treatment efficacy of budesonide was attributed solely to an effect on nonsmoking asthmatic subjects, since neither lung functions nor eosinophil markers changed in smokers even with high-dose budesonide. MPO but not LF was reduced after several months of treatment in all three groups, but only in nonsmokers. We conclude that ECP and EPX/EDN may be used to monitor antiinflammatory treatment in asthmatic patients, and that smoking asthmatic subjects are resistant to inhaled corticosteroids.
本研究的目的是探讨抗哮喘治疗对成年哮喘患者炎症血液标志物和肺功能的长期影响。为此,将85名过敏性和非过敏性哮喘患者随机分为三组,分别给予高剂量(1600微克/天)吸入布地奈德、低剂量(400微克/天)吸入布地奈德和口服氨茶碱(600毫克/天),并随访11个月,期间检测肺功能并采集血样,以检测血清中的嗜酸性粒细胞阳离子蛋白(ECP)、嗜酸性粒细胞蛋白X/嗜酸性粒细胞衍生神经毒素(EPX/EDN)作为嗜酸性粒细胞标志物,以及髓过氧化物酶(MPO)和乳铁蛋白(LF)作为中性粒细胞标志物。布地奈德以剂量依赖和时间平行的方式分别改善和降低了肺功能(预测FEV1%和组胺PC20)以及嗜酸性粒细胞标志物ECP和EPX/EDN。氨茶碱未改变肺功能,但长期治疗后降低了ECP和EPX/EDN。布地奈德的治疗效果仅归因于对不吸烟哮喘患者的作用,因为即使使用高剂量布地奈德,吸烟者的肺功能和嗜酸性粒细胞标志物也未改变。治疗数月后所有三组中MPO降低,但LF未降低,且仅在不吸烟者中出现。我们得出结论,ECP和EPX/EDN可用于监测哮喘患者的抗炎治疗,且吸烟哮喘患者对吸入性糖皮质激素耐药。