Abstract
Long-term, low-dose azithromycin reduces exacerbation frequency in chronic obstructive pulmonary disease (COPD), yet the mechanism remains unclear. This study characterised genome-wide gene expression changes in patients with neutrophilic COPD following long-term, low-dose azithromycin treatment.
Patients with neutrophilic COPD (>61% or >162×104 cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database.
In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses.
Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients.
Abstract
Azithromycin modifies gene expression in COPD http://ow.ly/Mqpv30lLXUM
Footnotes
This article has supplementary material available from openres.ersjournals.com
This study is registered at www.anzctr.org.au with identifier number ACTRN 12609000259246. Data sharing is not in place for this trial.
Conflict of interest: K.J. Baines has nothing to disclose.
Conflict of interest: T.K. Wright has nothing to disclose.
Conflict of interest: P.G. Gibson reports grants from NHMRC and personal fees from AstraZeneca, GlaxoSmithKline and Novartis, outside the submitted work.
Conflict of interest: H. Powell has nothing to disclose.
Conflict of interest: P.M. Hansbro has nothing to disclose.
Conflict of interest: J.L. Simpson reports grants from NHMRC during the conduct of the study.
Support statement: This project was supported by an NHMRC project grant.
- Received April 23, 2018.
- Accepted September 7, 2018.
- Copyright ©ERS 2018
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.