Diffuse panbronchiolitis in East Asia.
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.
Azuma
Arata
A
Respiratory Medicine of Nippon Medical School, Tokyo, Japan. a-azuma@nms.ac.jp
Kudoh
Shoji
S
D001988:Bronchiolitis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D005202:Asia, Eastern / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D018942:Macrolides / Q000627:therapeutic use*
D018942:Macrolides