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Is there a role for macrolides in severe asthma?

Brusselle, Guy G.a,b; Joos, Guya

Current Opinion in Pulmonary Medicine: January 2014 - Volume 20 - Issue 1 - p 95–102
doi: 10.1097/MCP.0000000000000017
ASTHMA: Edited by Nicola A. Hanania and Zuzana Diamant

Purpose of review: Severe asthma is a heterogeneous syndrome, encompassing several distinct clinical phenotypes. Different molecular and cellular pathways or endotypes determine the type of underlying airway inflammation in patients with severe asthma, which can be categorized as eosinophilic asthma (allergic and nonallergic) or noneosinophilic asthma (neutrophilic and paucigranulocytic). In this review, we discuss the potential role of macrolides in the treatment of severe asthma in adults.

Recent findings: Maintenance treatment with low-dose macrolides such as erythromycin and azithromycin provides clinical benefit in several chronic neutrophilic airway diseases, including cystic fibrosis (CF), non-CF bronchiectasis and exacerbation-prone chronic obstructive pulmonary disease. Although several short-term studies of macrolides in mild-to-moderate asthma have failed to improve lung function, the AzIthromycin in Severe Asthma trial has demonstrated a significant reduction in the rate of exacerbations in patients with exacerbation-prone noneosinophilic severe asthma. As chronic macrolide use is associated with the risks of population antimicrobial resistance, this add-on treatment should be restricted to severe asthma patients at greatest unmet need despite optimal asthma management.

Summary: Further clinical, translational and basic research is needed to better phenotype patients with severe asthma, to determine the risk–benefit ratio of macrolide maintenance treatment in neutrophilic severe asthma and to elucidate the principal mechanisms of action of macrolides.

aDepartment of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

bDepartment of Respiratory Medicine and Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence to Professor Dr Guy G. Brusselle, Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. E-mail: guy.brusselle@ugent.be

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins