儿童哮喘患者体内对氟替卡松和孟鲁司特反应的特征分析。

Characterization of within-subject responses to fluticasone and montelukast in childhood asthma.

作者信息

Szefler Stanley J, Phillips Brenda R, Martinez Fernando D, Chinchilli Vernon M, Lemanske Robert F, Strunk Robert C, Zeiger Robert S, Larsen Gary, Spahn Joseph D, Bacharier Leonard B, Bloomberg Gordon R, Guilbert Theresa W, Heldt Gregory, Morgan Wayne J, Moss Mark H, Sorkness Christine A, Taussig Lynn M

机构信息

Department of Pediatrics, National Jewish Medical and Research Medical Center and University of Colorado Health Sciences Center, Denver, CO 80206, USA.

出版信息

J Allergy Clin Immunol. 2005 Feb;115(2):233-42. doi: 10.1016/j.jaci.2004.11.014.

DOI:10.1016/j.jaci.2004.11.014

PMID:15696076

Abstract

BACKGROUND

Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients.

OBJECTIVE

We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other.

METHODS

Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 microg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers.

RESULTS

Defining response as improvement in FEV 1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20) and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC(20) and pulmonary function values.

CONCLUSIONS

Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs.

摘要

背景

哮喘患者对吸入性糖皮质激素（ICSs）和白三烯受体拮抗剂（LTRAs）的反应各不相同。

目的

我们试图确定个体对ICSs和LTRAs的反应是否一致，或者对一种药物无反应的哮喘患者对另一种药物是否有反应。

方法

在一项多中心、双盲、为期18周的试验中，将6至17岁的轻至中度持续性哮喘儿童随机分为2种交叉治疗顺序之一，包括接受8周的ICS丙酸氟替卡松（每日2次，每次100μg）治疗和8周的LTRA孟鲁司特（根据年龄每晚5 - 10mg）治疗。根据第1秒用力呼气容积（FEV₁）的改善情况评估反应，并评估其与基线哮喘表型相关生物标志物的关系。

结果

将反应定义为FEV₁改善7.5%或更高，126名参与者中17%对两种药物均有反应，23%仅对氟替卡松有反应，5%仅对孟鲁司特有反应，55%对两种药物均无反应。与对两种药物均无反应者相比，仅对氟替卡松有良好反应与呼出一氧化氮水平较高、总嗜酸性粒细胞计数较高、血清IgE水平较高、血清嗜酸性粒细胞阳离子蛋白水平较高以及乙酰甲胆碱PC₂₀水平较低和肺功能较低有关；仅对孟鲁司特有良好反应与年龄较小和病程较短有关。与孟鲁司特相比，对氟替卡松的差异反应更大与支气管扩张剂使用更多、支气管扩张剂反应、呼出一氧化氮水平和嗜酸性粒细胞阳离子蛋白水平较高以及乙酰甲胆碱PC₂₀和肺功能值较低有关。