Azuma Arata, Kudoh Shoji
Respiratory Medicine of Nippon Medical School, Tokyo, Japan.
Respirology. 2006 May;11(3):249-61. doi: 10.1111/j.1440-1843.2006.00845.x.
Diffuse panbronchiolitis is characterized by chronic sinobronchial infection and diffuse bilateral centrilobular lesions consisting of peribronchial infiltration of inflammatory cells. At present, it is known that diffuse panbronchiolitis is relatively restricted to East Asia. This uneven distribution is suspected to be highly associated with genetic predisposition located between human leucocyte antigen-A and -B loci. Low-dose, long-term macrolide therapy for the disease was suggested from a detailed observation of a single case that significantly improved by erythromycin therapy. Otherwise simple bactericidal activity of macrolides has been assumed as a candidate because of their clinical effect on the pathogenesis. In the last 10 years, the possible mechanism underlying the effectiveness of macrolide therapy has been dynamically investigated. To understand the pathological features and potential targets for macrolides in diffuse panbronchiolitis, the authors introduce the incidence of diffuse panbronchiolitis in East Asia, the profile of the disease and then trace the history of macrolide therapy in this review. The proposed mechanism of action includes the inhibition of excessive mucus and water secretion from the airway, the inhibition of neutrophil, and sometimes of lymphocyte and macrophage accumulating in the airway, the inhibition of transcription factors expressing several cytokines and the attenuation of bacterial virulence. Intracellular mechanisms of the action of macrolide are a hot topic of interest in research. The anti-inflammatory activity of macrolides is independent of their bactericidal effect, and a new anti-inflammatory analogue without antimicrobial activity should be developed to minimize the emergence of macrolide-resistant microorganisms and to maintain the safety of this treatment.
弥漫性泛细支气管炎的特征是慢性鼻窦支气管炎感染以及由炎症细胞的支气管周围浸润组成的双侧弥漫性小叶中心性病变。目前已知,弥漫性泛细支气管炎相对局限于东亚地区。这种分布不均被怀疑与位于人类白细胞抗原-A和-B位点之间的遗传易感性高度相关。通过对一例经红霉素治疗后显著改善的病例进行详细观察,提出了对该疾病采用低剂量、长期大环内酯类药物治疗的方法。此外,由于大环内酯类药物对发病机制的临床作用,其简单的杀菌活性也被视为一种可能。在过去十年中,人们对大环内酯类药物治疗有效性的潜在机制进行了积极研究。为了了解弥漫性泛细支气管炎中大环内酯类药物的病理特征和潜在靶点,作者在本综述中介绍了东亚地区弥漫性泛细支气管炎的发病率、疾病概况,然后追溯了大环内酯类药物治疗的历史。其提出的作用机制包括抑制气道中过多的黏液和水分分泌、抑制中性粒细胞,有时还抑制淋巴细胞和巨噬细胞在气道中的聚集、抑制表达多种细胞因子的转录因子以及减弱细菌毒力。大环内酯类药物作用的细胞内机制是研究中一个热门的感兴趣话题。大环内酯类药物的抗炎活性与其杀菌作用无关,应该开发一种没有抗菌活性的新型抗炎类似物,以尽量减少大环内酯类耐药微生物的出现,并维持这种治疗方法的安全性。