New life for macrolides

This article is an attempt to analyze and discuss the role and the purported mechanisms of azithromycin (AZM) in non-eosinophilic severe asthma, including antineutrophil activity, an effect on gastroesophageal reflux or antibacterial activity against an underlying chronic infection, such as Chlamydia pneumoniae. Macrolides have an expanding role in the therapy of chronic inflammatory diseases based on their additional anti-inflammatory and immunosuppressive properties. Many studies have been performed in lung transplantation field and maintenance treatment has been proved to be effective in cystic fibrosis, bronchiectasis, diffuse panbronchiolitis, and in bronchiolitis obliterans syndrome and in the prevention of exacerbations in patients with chronic obstructive pulmonary disease. Pathobiological studies of people with severe, refractory asthma focused on its heterogeneity encouraging more targeted and personalized approaches to asthma therapy. In neutrophilic asthma corticosteroids are not very effective, while the immunomodulatory action of macrolides is particularly relevant on neutrophils. Recently, The AZIthromycin in Severe ASThma (AZISAST) study, published on the April number of Thorax, provided evidences on the efficacy and safety of long-term add-on treatment with AZM in severe non-eosinophilic asthma. Despite concerns about an increased proportion of macrolide-resistant organism and about the effects of macrolides on cardiovascular events, there was no evidence of an increased risk of pneumonia or other adverse events. Because the AZISAST study was not able to demonstrate significant improvement in lung function and use of rescue medication, there is still a need for new data confirming the efficacy of AZM in severe non-eosinophilic asthma.