随机对照试验：三联吸入器疗法与双联吸入器疗法对吸烟哮喘患者小气道的影响。

Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics.

机构信息

Scottish Centre for Respiratory Research, School of Medicine, Ninewells Hospital, University of Dundee, Dundee, Scotland.

出版信息

Clin Exp Allergy. 2020 Oct;50(10):1140-1147. doi: 10.1111/cea.13702. Epub 2020 Jul 27.

DOI:10.1111/cea.13702

PMID:33180376

Abstract

BACKGROUND

Smoking worsens underlying asthma inflammation and also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control.

OBJECTIVES

We investigated the effects on small airways of adding long-acting beta-agonist (LABA) alone or with long-acting muscarinic antagonist (LAMA) to ICS in asthmatic smokers.

METHODS

Sixteen current smokers were enrolled: mean age 44 year, FEV1 84%, FEF25-75 47%, R5 158%, ACQ 1.69, 20 pack year . Patients were converted to a reference ICS as HFA-BDP during initial run-in at median dose of 800 µg/day. Open label olodaterol 5 µg od (OLO) or olodaterol 5 µg/tiotropium 5 µg od (OLO/TIO) was added to HFA-BDP for median duration of 3 weeks in a randomized cross over design, including run-in and washout periods on HFA-BDP. IOS and spirometry were measured after each treatment (BDP/OLO/TIO or BDP/OLO) and at baseline after run-in and washout (BDP).

RESULTS

After chronic dosing, IOS outcomes at trough except for R20 were all significantly improved with OLO/TIO compared to OLO. For the primary end-point of total airway resistance (as R5), the mean difference (95%CI) at trough was 0.06 (0.015-0.10) kPa/l/s, peripheral airways resistance (as R5-R20) 0.03 (0.003-0.06) kPa/l/s, peripheral lung reactance area (as AX) 0.38 (0.08-0.68) kPa/l and resonant frequency (as RF) 2.28 (0.45-4.12) Hz. FEF25-75 at trough was also better with OLO/TIO vs TIO: 0.93 (0.86 - 0.95) l/s while FEV1 was not different.

CONCLUSIONS

ICS/LABA/LAMA was superior to ICS/LABA on trough small airway outcomes in asthma patients who smoke.

摘要

背景

吸烟会加重潜在的哮喘炎症，还会导致对吸入性皮质类固醇（ICS）的耐药性。脉冲振荡法（IOS）测量的小气道功能障碍与控制效果较差有关。

目的

我们研究了在哮喘吸烟者中，ICS 中单独添加长效β-激动剂（LABA）或长效抗胆碱能药物（LAMA）对小气道的影响。

方法

纳入 16 名当前吸烟者：平均年龄 44 岁，FEV1 84%，FEF25-75 47%，R5 158%，ACQ 1.69，20 包年。患者在初始运行时转换为参考 ICS（HFA-BDP），中位剂量为 800μg/天。在随机交叉设计中，以开放标签奥洛他定 5μg 每日一次（OLO）或奥洛他定 5μg/噻托溴铵 5μg 每日一次（OLO/TIO）添加至 HFA-BDP，中位持续时间为 3 周，包括 HFA-BDP 的运行期和洗脱期。在每次治疗后（BDP/OLO/TIO 或 BDP/OLO）和运行期和洗脱期后的基线时测量 IOS 和肺活量计。

结果

在慢性给药后，与 OLO 相比，OLO/TIO 在谷值时所有 IOS 结果（除 R20 外）均显著改善。对于总气道阻力（R5）的主要终点，谷值时的平均差异（95%CI）为 0.06（0.015-0.10）kPa/l/s，周边气道阻力（R5-R20）为 0.03（0.003-0.06）kPa/l/s，周边肺反应面积（AX）为 0.38（0.08-0.68）kPa/l 和共振频率（RF）为 2.28（0.45-4.12）Hz。与 TIO 相比，OLO/TIO 在谷值时 FEF25-75 也更好：0.93（0.86-0.95）l/s，而 FEV1 没有差异。