多剂量干粉吸入器吸入福莫特罗一日两次与定量气雾剂吸入沙丁胺醇一日四次对持续性哮喘患者的疗效、耐受性及哮喘相关生活质量的影响：一项多中心、随机、双盲、双模拟、安慰剂对照的平行组研究。

Efficacy, tolerability, and effect on asthma-related quality of life of formoterol bid via multidose dry powder inhaler and albuterol QID via metered dose inhaler in patients with persistent asthma: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study.

作者信息

Busse William, Levine Bernard, Andriano Kim, Lavecchia Catherine, Yegen Umit

机构信息

Department of Allergy and Immunology, University of Wisconsin Medical School, Madison, Wisconsin, USA.

出版信息

Clin Ther. 2004 Oct;26(10):1587-98. doi: 10.1016/j.clinthera.2004.10.004.

DOI:10.1016/j.clinthera.2004.10.004

PMID:15598475

Abstract

BACKGROUND

Inhaled beta(2)-agonists are widely used in asthma treatment. The design limitations of pressurized metered dose inhalers (pMDIs) have prompted the development of dry powder inhalers (DPIs) for the delivery of asthma medications.

OBJECTIVE

The goal of this study was to evaluate the efficacy, tolerability, and effect on asthma-related quality of life (QOL) of a long-acting beta(2)-adrenoreceptor agonist, formoterol, delivered via multidose DPI, compared with albuterol delivered via pMDI or placebo in adolescents and adults with persistent asthma.

METHODS

This multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was conducted in outpatient clinics at 18 US centers. Adolescents and adults with persistent asthma received formoterol 10 pg BID via multidose DPI, albuterol 180 microg QID via pMDI, or placebo for 12 weeks. The primary efficacy variable was the 12-hour AUC of forced expiratory volume in 1 second (FEV(1)) after 12 weeks treatment. Secondary efficacy variables included asthma-related QOL, asthma symptom scores, rescue medication use, and other pulmonary function measures.

RESULTS

A total of 239 patients (147 females, 92 males; age range, 13-85 years) with persistent asthma were enrolled (formoterol, n = 80; albuterol, n = 79; placebo, n = 80). Formoterol delivered via the multidose DPI resulted in clinically relevant and statistically significant increases in 12-hour AUC of FEV(1) after 12 weeks of treatment compared with albuterol pMDI and placebo (P < 0.019 and P < 0.001, respectively). Asthma-related QOL (total score) was significantly improved with formoterol treatment compared with placebo (P < 0.015). Nocturnal asthma symptom scores significantly improved with formoterol compared with albuterol and placebo (P < 0.001 and P < 0.003, respectively) and rescue medication use was significantly less with formoterol compared with albuterol and placebo (P < 0.004 and P < 0.002, respectively). Treatment with formoterol was well tolerated.

CONCLUSIONS

In this study of adolescents and adults with persistent asthma, 12 weeks of treatment with formoterol 10 microg BID delivered via a multidose DPI provided significantly greater 24-hour bronchodilation compared with albuterol and placebo and resulted in significant improvements in asthma-related QOL compared with placebo. Formoterol was well tolerated in these patients.

摘要

背景

吸入性β₂受体激动剂广泛应用于哮喘治疗。压力定量吸入器（pMDIs）的设计局限性促使了干粉吸入器（DPIs）的研发，用于递送哮喘药物。

目的

本研究的目的是评估长效β₂肾上腺素能受体激动剂福莫特罗通过多剂量干粉吸入器递送，与沙丁胺醇通过压力定量吸入器递送或安慰剂相比，在持续性哮喘青少年和成人中对哮喘相关生活质量（QOL）的疗效、耐受性和影响。

方法

这项多中心、随机、双盲、双模拟、安慰剂对照、平行组研究在美国18个中心的门诊进行。持续性哮喘的青少年和成人接受通过多剂量干粉吸入器每日两次给予10μg福莫特罗、通过压力定量吸入器每日四次给予180μg沙丁胺醇或安慰剂，为期12周。主要疗效变量是治疗12周后1秒用力呼气量（FEV₁）的12小时药时曲线下面积（AUC）。次要疗效变量包括哮喘相关生活质量、哮喘症状评分、急救药物使用情况以及其他肺功能指标。

结果

共纳入239例持续性哮喘患者（14例女性，92例男性；年龄范围13 - 85岁）（福莫特罗组，n = 80；沙丁胺醇组，n = 79；安慰剂组，n = 80）。与沙丁胺醇压力定量吸入器和安慰剂相比，通过多剂量干粉吸入器递送的福莫特罗在治疗12周后导致FEV₁的12小时AUC有临床意义且在统计学上有显著增加（分别为P < 0.019和P < 0.001）。与安慰剂相比，福莫特罗治疗使哮喘相关生活质量（总分）显著改善（P < 0.015）。与沙丁胺醇和安慰剂相比，福莫特罗使夜间哮喘症状评分显著改善（分别为P < 0.001和P < 0.003），且与沙丁胺醇和安慰剂相比，福莫特罗的急救药物使用显著减少（分别为P < 0.004和P < 0.002）。福莫特罗治疗耐受性良好。