沙美特罗/氟替卡松和单用氟替卡松治疗哮喘1年对小气道功能影响的比较

Comparison of the Effects of Salmeterol/fluticasone versus Fluticasone over 1-year on Small Airway Functions in Asthmatics

目的比较沙美特罗与氟替卡松联用(SFC)和单用氟替卡松(FC)治疗哮喘52周对小气道功能的影响。方法采用随机、分层、双盲、平行分组对照研究方法,将34例未控制的哮喘患者随机分配至 SFC 组(n=18)或单用 FC 组(n=16)。按既往吸入糖皮质激素剂量不同,起始药物剂量不同。治疗逐步升级至达到哮喘完全控制(或吸入 FC 至最大剂量500 μg,每日两次),共治疗52周。比较治疗后4、12、24、36、48及52周小气道功能指标呼出50%肺活量时流速(FEF50)、呼出75%肺活量时流速(FEF75)、最大呼气中期流速(MMEF)和哮喘常规肺功能观察指标1秒钟用力呼气容积(FEV_1)和最大呼气流量(PEF)的变化,以及这些指标的改善率达到12%的两组间差异。结果 SFC 组治疗4周时,FEF50、FEF75和 MMEF 分别为(2.09±0.95)、(0.70±0.47)和(1.67±0.87)L/s,与治疗前的(1.70±0.76)、(0.58±0.34)和(1.37±0.70)L/s 相比差异有显著性,且此后各次随访指标与治疗前相比差异均有显著性(P 均<0.05);FC 组治疗12周时,才出现与治疗前比较差异有显著性的指标(P 均<0.05)。治疗4周时,SFC 组的 FEF50、FEF75和 MMEF 改善率≥12%的比率分别为77.8%、66.7%和72.2%,明显高于 FC 组的43.8%、20.0%和37.5%(P 均<0.05)。治疗52周时,SFC 组和 FC 组分别有100%和75%的患者 FEF50改善率≥12%,两组相比差异有显著性(P<0.05)。治疗后52周,SFC 组和 FC 组分别有72.2%和37.5%的患者FEV_1改善率≥12%,两组相比差异也有显著性(P<0.05)。结论与单用 FC 比较,SFC 对未控制的哮喘患者小气道功能的改善更有效、更迅速。

Objective To compare the effects of inhalation of salmeterol/fluticasone with fluticasone propionate monotherapy on small airway functions of patients with uncontrolled asthma. Methods In this randomized, stratified, double-blind, and parallel-group study, 34 symptomatic asthmatics patients were randomly divided into 2 groups and received either salmeterol/fluticasone （n = 18） or fluticasone （n = 16） twice daily respectively, via a single Diskus inhaler for 52 weeks. The initial dosage of inhaled corticosteroid at the randomization for each patient was determined according to their individual treatment before the study. The dosage of fluticasone was stepped-up until totally controlled asthma was achieved （or maximum 500 μg fluticasone twice a day）. Forced expiratory flow at 50% of vital capacity （FEF50）, forced expiratory flow at 75% of vital capacity （FEF75）, maximum midexpiratory flow rate （MMEF） and forced expiratory volume during the first second （FEV1）, and peak expiratory flow （PEF） at the baseline and the end of 4, 12, 24, 36, 48, and 52 weeks of treatment were evaluated, as well as the number of patients who achieved 12% improvement in these parameters. Results FEF50, FEF75, and MMEF （2.09±0.95, 0.70±0.47 and 1.67 ± 0.87 L/s, respectively） were significantly increased at the end of week 4 compared with baseline （1.70 ± 0.76, 0.58 ± 0.34 and 1.37 ± 0.70 L/s, respectively） and remained in the subsequent follow-ups with combination inhaled salmeterol/fluticasone, whereas no significant increases in FEF50, FEF75, and MMEF were observed until the end of week 12 with inhaled fluticasone. There were 77.8%, 66.7%, and 72.2% of patients respectively with inhalation of salmeterol/fluticasone achieved a 12% improvement in FEF50, FEF75, and MMEF at the end of week 4, compared with 43.8%, 20.0%, and 37.5% with fluticasone alone （all P 〈 0.05）. 100% of the patients with salmeterol/fluticasone achieved a 12% improvement in FEF50 at the end of week 52, whereas only 75% with fluticasone （P 〈 0.05）. At the end of week 52, 72.2% and 37.5% of the patients achieved a 12% improvement in FEV1 with salmeterol/ fluticasone group and fluticasone alone respectively and the difference was statistically significant too. Conclusion For improving small airway functions in patients with uncontrolled asthma, almeterol/ fluticasone is more effective and the improvement achieved more rapidly compared with fluticasone alone.