Macrolides for yet another chronic airway disease: severe asthma?
- Correspondence to Dr Peter G Gibson, Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW 2310, Australia;
- Received 17 December 2012
- Accepted 17 December 2012
- Published Online First 24 January 2013
Macrolides have a macrocyclic lactone ring, whose size and features have been modified from the 14 carbon structure of erythromycin in order to develop newer agents such as azithromycin (AZM). They were originally derived from products the microbial order Actinomycetales (Saccharopolyspora erythrae, formerly Streptomyces erythrae), and are yet another respiratory harvest from the organism that have given us many antibiotics, starting with the important antituberculosis drug, streptomycin. Macrolides are widely used as antibiotics, and now form part of guideline-recommended therapy in community-acquired pneumonia. They have an expanding role in the therapy of chronic inflammatory diseases based on their additional anti-inflammatory and immunosuppressive properties. Further development has produced broad-spectrum antibacterials, such as AZM, with a longer half-life, and minimal inhibition of cytochrome CYP3A4 and, hence, fewer drug interactions. Other developments in this class include tacrolimus and its derivatives that target macrophyllin-12 (FK506 binding protein) and are potent immunosuppressive agents.
The classical airway disease that responds to long-term low-dose macrolide therapy is diffuse panbronchiolitis in Asian populations.1 The pathological lesion is centred around the bronchioles and involves intense chronic inflammation, typically neutrophilic, leading to mucus hypersecretion, progressive loss of lung function, bacterial airway infection, and often death. Building on this paradigm, macrolides have been found to be effective in other airway …