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Macrolide antibiotics have been demonstrated to be efficacious in diverse chronic airway diseases characterised by neutrophilic airway inflammation, encompassing cystic fibrosis (CF), non-CF bronchiectasis, diffuse panbronchiolitis, exacerbation-prone COPD and neutrophilic severe asthma.1–8 Many exogenous and endogenous factors can elicit airway neutrophilia: infections (bacterial, viral, virus-like …), pollution (smoking, indoor and outdoor air pollution) and other factors (eg, auto-immunity, gastro-oesophageal reflux with aspiration). Macrolides such as erythromycin, clarithromycin and azithromycin not only have antimicrobial properties, but also broad anti-inflammatory and immunomodulatory effects.9 The antimicrobial effects of macrolides include direct bacterial killing, the prevention of biofilm formation by interfering with microbial quorum sensing, and the stimulation of phagocytosis of bacteria by macrophages. However, chronic use of macrolides has been associated with the occurrence of macrolide-resistant bacteria in the commensal flora of the pharynx of individual patients, and also induces the risk of an increase in antibiotic resistance at the population level.10 Therefore, it is crucial to address the research question whether the antimicrobial properties of macrolides are necessary for their therapeutic efficacy in chronic neutrophilic airway diseases. If not, then the development and use of non-antibiotic macrolides is warranted, since these novel drugs would retain the therapeutic efficacy without the risk of inducing microbial resistance.
In the current issue of Thorax, two complimentary papers address thoroughly the therapeutic potential of macrolides in two different chronic airway diseases which represent a high unmet medical need: bronchiolitis obliterans syndrome (BOS) after lung transplantation and steroid-resistant severe asthma. In the first paper, Corris et al11 performed the first randomised controlled trial of azithromycin in the treatment of BOS post lung transplantation. In the second paper, Essilfie et al12 investigated the effects of clarithromycin in two mouse models of steroid-resistant asthma, and investigated in depth the mechanisms of action.
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