近日，新西兰医学研究所Richard Beasley教授及其研究小组，比较了布地奈德-福莫特罗缓解疗法与布地奈德维持+特布他林缓解疗法治疗成人轻中度哮喘的疗效。研究结果于8月23日在线发表于《柳叶刀》。

研究小组在新西兰的15个医疗保健单位进行了为期52周的开放标签、平行组、多中心、优越性的随机对照试验。参与者是18-75岁的成年哮喘病患者，在此前的12周，无论是否维持吸入低中剂量的皮质类固醇，他们都使用短效β-激动剂（SABA）来缓解症状。

哮喘重度急性发作定义为因哮喘使用全身皮质类固醇至少3天，或因哮喘需要进行全身皮质类固醇治疗而住院或挂急诊。

2016年5月4日至2017年12月22日，885名受试者按照1：1随机分为两组，437名分配到布地奈德-福莫特罗组（按需吸入布地奈德200μg+福莫特罗6μg），448名分配到布地奈德维持+特布他林组（每日吸入两次布地奈德200μg，按需吸入特布他林250μg）。

布地奈德-福莫特罗组每年每名患者的哮喘重度急性发作率为0.119，低于布地奈德维持+特布他林组（0.172）。两组患者最常见的不良反应为鼻咽炎，其中布地奈德-福莫特罗组中有154人（35%）发生鼻咽炎，布地奈德维持+特布他林组中有144人（32%）。

在成人轻中度哮喘患者中，按需吸入布地奈德-福莫特罗比低剂量布地奈德维持治疗联合按需吸入特布他林可更有效地预防重度急性发作。该发现有力地支持了2019年全球哮喘防治创议的建议。

据悉，对于成人轻度哮喘，与SABA缓解疗法相比，吸入皮质类固醇联合快速起效的长效β-激动剂（LABA）的缓解单药疗法可减少重度哮喘急性发作。

附：英文原文

Title: Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial

Author: Jo Hardy, BMBCh *,Christina Baggott, MBChB *,James Fingleton, PhD,Prof Helen K Reddel, PhD,Prof Robert J Hancox, MD,Matire Harwood, PhD,Andrew Corin, MBChB,Jenny Sparks, MSc,Daniela Hall, BMBS,Doñah,Sabbagh, BMBCh,Saras Mane, BMBCh,Alexandra Vohlidkova, MBBS,John Martindale, BSc,Mathew Williams, Dip Ex Sci,Philippa Shirtcliffe, MBChB,Mark Holliday, BSc,Prof Mark Weatherall, MApplStats,Prof,Richard Beasley, DSc,on behalf of the PRACTICAL study team

Issue&Volume: 23 August 2019

Summary : 

Background

In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide–formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline.

Methods

We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18–75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg–formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437.

Findings

Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide–formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide–formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48–1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide–formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed.

Interpretation

In adults with mild to moderate asthma, budesonide–formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid–formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma.

DOI: https://doi.org/10.1016/S0140-6736(19)31948-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31948-8/fulltext#