激素治疗对运动诱发性哮喘患者痰嗜酸性粒细胞计数的影响

The influence of inhaled corticosteroid therapy on the enumeration of sputum eosinophils in exercise-induced asthma

目的探讨气道嗜酸性粒细胞性炎症和运动诱发的支气管痉挛(EIB)之间的关系,及其对吸入糖皮质激素(ICS)治疗的反应。方法本研究为随机、双盲、二阶段交叉试验,将26例有运动诱发性支气管痉挛发作史且从未接受过激素治疗的哮喘患者随机分为两组,每组分别给予两个剂量水平的布地奈德吸入:①100μg/d与400μg/d对比;②200μg/d与800μg/d对比。每一阶段为3周,洗脱期3～8周。治疗前及开始治疗后每隔1周进行1次运动激发试验并留取痰液标本行嗜酸性粒细胞计数。结果高剂量ICS治疗(400μg/d和800μg/d)可显著减少痰嗜酸性粒细胞比例。痰嗜酸性粒细胞百分比与运动诱发性支气管痉挛严重程度相关,且对EIB的严重程度有预测作用;高剂量ICS治疗时,尚可预测EIB对激素治疗有效,而对低剂量ICS组(100μg/d和200μg/d)则无预测作用。低剂量ICS治疗,不管基线痰嗜酸性粒细胞计数是否增多,EIB在第1周末发作显著减轻,尔后几无改善。而高剂量ICS治疗对EIB的改善作用在痰嗜酸性粒细胞增多的患者中显著优于嗜酸性粒细胞计数小于5%者,这种明显的差异在开始治疗1周后即显现,且随时间的推移而继续加大。结论气道嗜酸性粒细胞性炎症可能在EIB的发生及其对ICS治疗有效的调节机制中起重要的作用。测定痰嗜酸性粒细胞计数在预测EIB的严重程度及其对不同剂量ICS治疗的反应具有一定的临床应用价值。

Objective To investigate the relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction（EIB）,and the response to inhaled corticosteroids（ICS） therapy.Methods Twenty-six steroid-naive asthmatic patients with EIB were randomized into two parallel,double-blind,cross-over study arms.Each arm compared two doses of inhaled budesonide that were administered for 3 weeks with a washout period of 3 to 8 weeks,namely（1） 100 vs 400 μg daily;and（2） 200 vs 800 μg daily.Baseline and weekly assessments with exercise challenge and sputum analysis were performed.Results Only high-dose ICS therapy（300 and 400 μg） significantly attenuated the percentage of sputum eosinophil.The percentage of sputum eosinophil was significantly correlated with EIB severity.The percentage of sputum eosinophil also predicted the magnitude and temporal response of EIB to high-dose therapy,but not to low-dose therapy（ie,100 and 200 μg）.Low-dose ICS therapy significantly reduced EIB at the 1st week,with little additional improvement thereafter and irrespective of baseline sputum eosinophil counts.In contrast,a high-dose ICS therapy provided a significantly greater improvement in EIB in subjects with sputum eosinophilia compared to those with an eosinophil count of 5%.The difference was evident after the first week of high-dose ICS therapy and increased with time.Conclusion Eosinophilic airway inflammation may modify the severity of EIB and the response to ICS therapy.The percentage of sputum eosinophil may,therefore,be used in predicting the magnitude and temporal response of EIB to different dose levels of ICSs.