Palmqvist M, Bruce C, Sjöstrand M, Arvidsson P, Lötvall J
Section of Allergy, The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden.
Allergy. 2005 Jan;60(1):65-70. doi: 10.1111/j.1398-9995.2005.00633.x.
Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.
对变应原的早期哮喘反应(EAR)和迟发哮喘反应(LAR)是由一系列支气管收缩介质的局部释放所诱发的,这些介质包括白三烯和组胺。抗白三烯药物和其他抗哮喘药物,如吸入性糖皮质激素,均已显示可减轻EAR和LAR。本研究的目的是直接比较口服抗白三烯药物孟鲁司特(Mont;每日一次,每次10 mg,共8天)和吸入性糖皮质激素[丙酸氟替卡松(FP),每日两次,每次250 μg,共8天]常规治疗对吸入变应原激发后的EAR和LAR的影响。在筛查访视时记录有EAR和LAR的患者以双盲、双模拟、交叉方式随机接受这些治疗或安慰剂治疗。在治疗的第八天给予能同时引起EAR和LAR的剂量的变应原激发。在EAR期间,安慰剂治疗时FEV1的最大下降为17.8%,Mont治疗时为8.3%,FP治疗时为16.3%(Mont与安慰剂相比,P<0.05)。在LAR期间,安慰剂治疗时最大下降为13.8%,Mont治疗时为11.8%,FP治疗时为2%(FP与安慰剂相比,P<0.05;FP与Mont相比,P<0.05)。与Mont相比,FP治疗后变应原激发24小时后乙酰甲胆碱激发浓度(PC20)显著更高(P<0.05)。与安慰剂治疗相比,孟鲁司特和氟替卡松均可降低变应原激发后痰液嗜酸性粒细胞的相对数量。本研究表明,抗白三烯药物可有效减轻EAR,而吸入性糖皮质激素在减轻EAR方面比抗白三烯药物更有效,且能在更大程度上改善支气管高反应性。总之,在轻度哮喘患者中,吸入性糖皮质激素在减轻变应原诱导的气道反应方面总体疗效优于口服抗白三烯药物。