吸入糖皮质激素哮喘患者高和低剂量过敏原激发试验
2014/11/05
摘要
目的:吸入过敏原激发模型之前一直被用于探究新型抗炎药物在吸入激素(ICS)初治哮喘患者中的疗效。本研究旨在描述对于正在使用ICS治疗的哮喘患者中,高和低剂量过敏源激发试验的特点。
方法:28例正在使用ICS的哮喘患者接受高剂量过敏原激发试验,其中10例随后接受重复低剂量激发试验,包括7个过敏源激发试验。收集诱导痰液以检测细胞数和上清液生物标记物。
结果:高剂量过敏原激发试验导致28例中19例有早发和迟发哮喘反应;FEV1平均最大下降分别为29.1%(SD 6.2%)和25.1%(SD 9.6%)。痰中嗜酸性粒细胞增加6.2%(p=0.0004),浮层嗜酸细胞阳离子蛋白(ECP)水平也同样增加。低剂量过敏原激发试验导致FEV1快速下降,但是在激发试验或痰液检测后24小时对FEV1无影响。
结论:ICS哮喘患者的高剂量过敏原激发试验诱导了与嗜酸性粒细胞气道炎症增加相关的迟发哮喘反应。以上提示,对于在ICS维持治疗的基础上加用新型抗炎药物的疗效研究,这可能是一个适用模型。
(林江涛 审校)
Br J Clin Pharmacol. 2014 Sep 11. doi: 10.1111/bcp.12508. [Epub ahead of print]
High and low dose allergen challenges in asthma patients using inhaled corticosteroids
Lee WY1, Southworth T, Booth S, Singh D
ABSTRACT
AIMS: The inhaled allergen challenge model has previously been used to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS) naïve asthmatics. The aim of this study was to characterise high and low dose allergen challenges in asthma patients using ICS.
METHODS: 28 asthma patients taking ICS (beclomethasone equivalent <1000 mcg/day) were recruited for high dose allergen challenge, of which 10 subsequently also had a repeat low dose challenge comprising 7 allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers.
RESULTS: The high dose allergen challenge caused an early and late asthmatic response in 19 out of 28 patients; the mean maximum fall in FEV1 was 29.1% (SD 6.2%) and 25.1% (SD 9.6%) respectively. There was also an increase in sputum eosinophils of 6.2% (p=0.0004), as well as supernatant ECP levels. The low dose allergen challenge caused an acute fall in FEV1 , but had no effect on FEV1 at 24 hrs after challenge or sputum measurements.
CONCLUSIONS: The high dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment.
Br J Clin Pharmacol. 2014 Sep 11. doi: 10.1111/bcp.12508. [Epub ahead of print]
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