Amayasu H, Yoshida S, Ebana S, Yamamoto Y, Nishikawa T, Shoji T, Nakagawa H, Hasegawa H, Nakabayashi M, Ishizaki Y
Department of Medicine, Yokohama Rosai Hospital, Japan.
Ann Allergy Asthma Immunol. 2000 Jun;84(6):594-8. doi: 10.1016/S1081-1206(10)62409-X.
Although long-term administration of 14-membered macrolide antibiotics is a therapeutic alternative in asthma, both its pharmacologic mechanism of action and association with the pathogenesis of asthma remain obscure.
This study investigated the suppressive effect of clarithromycin on airway responsiveness to methacholine provocation testing and examined whether chrarithromycin's antiasthmatic activity is associated with a reduction in eosinophilic inflammation.
For 8 weeks, patients received 200 mg of clarithromycin or identical-appearing placebo twice daily. We assessed the effects of treatment with clarithromycin on bronchoconstriction precipitated by inhalation of methacholine in 17 adults with mild or moderate bronchial asthma who were in stable clinical condition. A double-blind, randomized, crossover design was used. Eosinophil counts and eosinophilic cationic protein (ECP) levels were determined in blood and sputum samples obtained on the morning of the methacholine provocation testing day.
After 8 weeks of treatment with clarithromycin, patients' symptoms, blood and sputum eosinophils counts and sputum ECP levels were significantly decreased compared with both placebo and baseline. Furthermore, values of PC20 methacholine improved in all patients after clarithromycin treatment.
Clarithromycin has a bronchial anti-inflammatory effect associated with decreased eosinophilic infiltration. This study suggests interesting therapeutic possibilities for bronchial asthma that warrant further trials.
尽管14元大环内酯类抗生素的长期给药是哮喘治疗的一种选择,但其药理作用机制以及与哮喘发病机制的关联仍不明确。
本研究调查了克拉霉素对乙酰甲胆碱激发试验气道反应性的抑制作用,并检验克拉霉素的抗哮喘活性是否与嗜酸性粒细胞炎症的减轻相关。
患者连续8周每日两次服用200毫克克拉霉素或外观相同的安慰剂。我们评估了克拉霉素治疗对17例临床病情稳定的轻度或中度支气管哮喘成年患者吸入乙酰甲胆碱诱发的支气管收缩的影响。采用双盲、随机、交叉设计。在乙酰甲胆碱激发试验当天上午采集的血液和痰液样本中测定嗜酸性粒细胞计数和嗜酸性粒细胞阳离子蛋白(ECP)水平。
与安慰剂和基线相比,克拉霉素治疗8周后,患者的症状、血液和痰液嗜酸性粒细胞计数以及痰液ECP水平均显著降低。此外,克拉霉素治疗后所有患者的乙酰甲胆碱PC20值均有所改善。
克拉霉素具有支气管抗炎作用,与嗜酸性粒细胞浸润减少有关。本研究提示支气管哮喘存在有趣的治疗可能性,值得进一步试验。