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

在日本，长期小剂量大环内酯类药物治疗是治疗慢性鼻窦炎(CRS)的基本和标准药物疗法，尤其是对中性粒细胞占优势的类型，而不是嗜酸性粒细胞占优势的类型。红霉素是一种14元大环内酯类药物，最初被广泛用于CRS的治疗。后来，克拉霉素(CAM)和罗红霉素(RXM)这两种新的14元大环内酯类药物在20世纪90年代开始实际使用。至于大环内酯类药物对CRS的作用机制，抗炎作用比抗生素作用重要得多；大环内酯类化合物抑制炎症黏膜部位IL-8的产生，抑制中性粒细胞的募集和活化。近年来，在CRS合并鼻息肉(CRSwNP)中，有30%~40%的难治性病例出现明显的鼻息肉或鼻窦粘膜嗜酸性粒细胞浸润。术后口服类固醇是目前唯一有效和实用的治疗此类CRS“缓解诱导”的方法。然而，长期或大剂量口服类固醇会导致胃溃疡、月亮面、骨质疏松和感染易感性等不良副作用。本研究旨在从实验和临床两个方面阐明大环内酯对类固醇的启动作用。在本次实验和临床试验中，CAM被选为具有代表性的14元大环内酯类化合物。对于试验中的类固醇，实验中使用了地塞米松(DEX)，临床上开了类固醇喷雾剂莫米松或倍他米松。在实验和临床上，CAM的启动效果取决于具体情况。在难治性CRS病例中，哪些病例有资格接受大环内酯类激素类药物的启动治疗，有待进一步研究。

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.