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New therapy for refractory chronic sinusitis in application with priming effect of macrolide on steroid therapy

大环内酯类药物启动效应应用治疗难治性慢性鼻窦炎的新疗法

基本信息

批准号：
22591901
负责人：
MATSUNE Shoji
金额：
$ 2.41万
依托单位：
Nippon Medical School (2011-2012)Kagoshima University (2010)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

In Japan long term low dose macrolide therapy is now a fundamental and standard pharmacotherapy for chronic rhiosinusitis (CRS), especially in neutrophil rather than eosinophil dominant type. Erythromycin, 14-memmbered macrolide, was originally and prevalently used as an appropriate macrolide therapy for CRS. Later, clarithromycin (CAM) and roxithromycin (RXM), new 14-membered macrolide, became practically in use in1990s. As to the mechanism of macrolide effects on CRS, anti-inflammation is regarded to be much more important than antibiotic effects; macrolide suppresses IL-8 production at the site of inflammatory mucosa and inhibits recruit and activation of neutrophils. Recently, quite refractory cases with pronounced eosinophil infiltration in nasal polyps or sinus mucosa are seen in 30~40% among CRS with nasal polyps (CRSwNP). Postoperative oral steroid is now only effective and practical therapy for “remission induction” of this type of CRS. However, long term or high dose oral steroids induce harmful side effects such as stomach ulcer, moon face, osteoporosis and susceptibility to infection. This study was designed in order to elucidate the priming effect of macrolide on steroids experimentally and clinically. In this experimental and clinical trials, CAM was chosen as a representative 14-membered macrolides. For steroids in the trials, Dexamethasone (DEX) was used in experiments and steroid nasal spray, Mometasone or Betamethasone, was prescribed clinically. Experimentally and clinically, priming effect of CAM was depending on the case. Further study is necessary to delineate in details what kind ofcases among refractory CRS cases are eligible for priming effect of macrolide on steroidtherapy.

在日本，长期低剂量大环内酯类药物治疗现已成为慢性鼻窦炎 (CRS) 的基本和标准药物治疗，尤其是中性粒细胞而非嗜酸性粒细胞占主导地位的类型。红霉素是一种 14 元大环内酯类药物，最初广泛用作治疗 CRS 的合适大环内酯类药物。后来，克拉霉素（CAM）和罗红霉素（RXM）等新型14元大环内酯类药物在20世纪90年代开始实用化。就大环内酯类药物治疗CRS的机制而言，抗炎作用被认为比抗生素作用更为重要；大环内酯类药物可抑制炎症粘膜部位 IL-8 的产生，并抑制中性粒细胞的募集和活化。近年来，鼻息肉或鼻窦粘膜明显嗜酸性粒细胞浸润的难治性病例，在伴有鼻息肉的慢性鼻窦炎（CRSwNP）中占30%~40%。目前，术后口服类固醇是此类 CRS“诱导缓解”的唯一有效且实用的疗法。然而，长期或大剂量口服类固醇会引起有害的副作用，如胃溃疡、圆脸、骨质疏松和易感染等。本研究旨在通过实验和临床阐明大环内酯类药物对类固醇的启动作用。在本次实验和临床试验中，选择CAM作为具有代表性的14元大环内酯类药物。对于试验中的类固醇，实验中使用地塞米松（DEX），临床上则使用类固醇鼻喷雾剂莫米松或倍他米松。实验和临床上，CAM的启动效应视具体情况而定。需要进一步研究来详细说明难治性 CRS 病例中哪些病例适合大环内酯类固醇治疗的启动效应。