克拉霉素通过抑制中性粒细胞性炎症治疗难治性哮喘
2008/04/30
难治性哮喘即使在吸入大剂量糖皮质激素和长效支气管扩张剂的情况下仍有持续症状，目前对这种难治性哮喘的辅助治疗手段有限。大环内酯类抗生素如克拉霉素在体外研究中发现有抗IL-8和中性粒细胞的作用，而这些炎症介质在非嗜酸性粒细胞性哮喘中有重要作用。
因此，大环内酯类抗生素有望作为难治性哮喘的辅助治疗。Simpson JL等对克拉霉素在治疗重度难治性哮喘尤其是非嗜酸性粒细胞性哮喘中的作用进行了观察。该研究入选了45例重度难治性哮喘患者，随机给予克拉霉素（500mg，2次/日）或安慰剂治疗8周。通过诱导痰中性粒细胞计数，测定诱导痰中IL-8、中性粒细胞弹性蛋白酶和基质金属蛋白酶（MMP）-9水平，并评估患者临床表现，包括肺功能、气道反应性，哮喘症状控制以及生活质量。
结果发现，与安慰剂组相比，克拉霉素治疗组气道IL-8水平和中性粒细胞数明显降低，生活质量评分改善，诱导痰中中性粒细胞弹性蛋白酶和MMP-9浓度也降低，尤其是难治性非嗜酸性粒细胞性哮喘患者降低更为明显。
因此，作者认为大环内酯类可作为难治性哮喘尤其是非嗜酸性粒细胞性哮喘的辅助治疗。
（王苹莉 浙江医科大学附属第二医院呼吸科 310009 摘译）
（Am J Respir Crit Care Med. 2008;177:148-155）
Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG. Clarithromycin targets neutrophilic airway inflammation in refractory asthma.Am J Respir Crit Care Med. 2008 Jan 15;177(2):148-55.
RATIONALE: Patients with refractory asthma have persistent symptoms despite maximal treatment with inhaled corticosteroids and long-acting bronchodilators. The availability of add-on therapies is limited, and effective add-on therapies that target noneosinophilic airway inflammation are needed. Macrolide antibiotics, such as clarithromycin, have in vitro efficacy against IL-8 and neutrophils, key inflammatory mediators in noneosinophilic asthma.
OBJECTIVES: To determine the efficacy of clarithromycin in patients with severe refractory asthma and specifically in a subgroup of patients with noneosinophilic asthma. METHODS: Subjects with severe refractory asthma (n = 45) were randomized to receive clarithromycin (500 mg twice daily) or placebo for 8 weeks.
MEASUREMENTS AND MAIN RESULTS: The primary outcome for this study was sputum IL-8 concentration. Other inflammatory outcomes assessed included sputum neutrophil numbers and concentrations of neutrophil elastase and matrix metalloproteinase (MMP)-9. Clinical outcomes were also assessed, including lung function, airway hyperresponsiveness to hypertonic saline, asthma control, quality of life, and symptoms. Clarithromycin therapy significantly reduced airway concentrations of IL-8 and neutrophil numbers and improved quality-of-life scores compared with placebo. Reductions in neutrophil elastase and MMP-9 concentrations were also observed. These reductions in inflammation were most marked in those with refractory noneosinophilic asthma.
CONCLUSIONS: Clarithromycin therapy can modulate IL-8 levels and neutrophil accumulation and activation in the airways of patients with refractory asthma. Macrolide therapy may be an important additional therapy that could be used to reduce noneosinophilic airway inflammation, particularly neutrophilic inflammation, in asthma. Clinical trial registered with the Australian Clinical Trials Registry
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