一项关于小颗粒吸入类固醇治疗难治性嗜酸性粒细胞哮喘 (SPIRA)的随机对照试验.
2015/06/18
摘要
背景：有证据表明：一些难治性哮喘患者的远端气道存在不受控制的嗜酸性粒细胞炎症。然而传统的吸入类固醇配方主要到达大气道，具有超细粒度的新配方则能到达末梢气道。专门治疗远端气道炎症可能改善哮喘控制。
方法：本研究共纳入30例存在持续气道嗜酸性粒细胞增多的难治性哮喘患者。尽管使用高剂量吸入类固醇，这些患者的哮喘仍然难以控制。使用两周泼尼松龙30mg之后，哮喘控制有所改善的患者随机接受为期8周的环索奈德（320 µg，每日两次）加常规泼尼松龙维持治疗或安慰剂加常规泼尼松龙维持治疗。主要的观察指标是第八周的痰液嗜酸性粒细胞数。肺泡一氧化氮作为远端气道炎症的标志物被测定。
结果：环索奈德组痰液嗜酸性粒细胞数持续被抑制(中值2.3%)，而安慰剂组痰液嗜酸性粒细胞数没有被抑制（中值4.5%），尽管组间差异并不显著。当排除了试验中改变维持性泼尼松龙剂量的患者后，组间差异显著(1.4% vs 4.5%, p=0.028)。尽管环索奈德组的肺泡一氧化氮降低，但数值没有统计学意义。
结论：这些数据证明：伴有持续性嗜酸性粒细胞炎症的哮喘患者不是真正难以治疗的，额外吸入皮质类固醇可能会维持对气道嗜酸性粒细胞数目的抑制。进一步的工作需要关注以患者为本的测量结果如哮喘急性发作率及额外的小气道功能测试。
（苏欣 审校）
Thorax. 2015 Apr 9. pii: thoraxjnl-2014-206481.doi:10.1136/thoraxjnl-2014-206481. [Epub ahead of print]
A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA).
Hodgson D1, Anderson J1, Reynolds C1, Meakin G1, Bailey H1, Pavord I2, Shaw D1, Harrison T1.
Abstract
BACKGROUND:Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control.
METHODS:30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation.
RESULTS:There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance.
CONCLUSIONS:These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function.
Thorax. 2015 Apr 9. pii: thoraxjnl-2014-206481.doi:10.1136/thoraxjnl-2014-206481. [Epub ahead of print]
