title: The role of macrolides in asthma: current evidence and future directions.
abstract: Macrolides, such as clarithromycin and azithromycin, possess antimicrobial, immunomodulatory, and potential antiviral properties. They represent a potential therapeutic option for asthma, a chronic inflammatory disorder characterised by airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Results from clinical trials, however, have been contentious. The findings could be confounded by many factors, including the heterogeneity of asthma, treatment duration, dose, and differing outcome measures. Recent evidence suggests improved effectiveness of macrolides in patients with sub-optimally controlled severe neutrophilic asthma and in asthma exacerbations. We examine the evidence from clinical trials and discuss macrolide properties and their relevance to the pathophysiology of asthma. At present, the use of macrolides in chronic asthma or acute exacerbations is not justified. Further work, including proteomic, genomic, and microbiome studies, will advance our knowledge of asthma phenotypes, and help to identify a macrolide-responsive subgroup. Future clinical trials should target this subgroup and place emphasis on clinically relevant outcomes such as asthma exacerbations.
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK; Centre for Respiratory Infection, London, UK; Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Ernie H C
authors.initials: EH
authors.lastname: Wong
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK; Centre for Respiratory Infection, London, UK.
authors.forename: James D
authors.initials: JD
authors.lastname: Porter
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK; Centre for Respiratory Infection, London, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK; Centre for Respiratory Infection, London, UK; Imperial College Healthcare NHS Trust, London, UK. Electronic address: s.johnston@imperial.ac.uk.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D000890:Anti-Infective Agents / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D018942:Macrolides / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D009093:Mucus / Q000187:drug effects; D010641:Phenotype; D016032:Randomized Controlled Trials as Topic
chemical_list: D000890:Anti-Infective Agents; D018942:Macrolides