Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD
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. Pa...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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European Respiratory Society
2018-11-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/4/4/00031-2018.full |
| _version_ | 1811254937370230784 |
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| author | Katherine J. Baines Thomas K. Wright Peter G. Gibson Heather Powell Philip M. Hansbro Jodie L. Simpson |
| author_facet | Katherine J. Baines Thomas K. Wright Peter G. Gibson Heather Powell Philip M. Hansbro Jodie L. Simpson |
| author_sort | Katherine J. Baines |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T17:16:04Z |
| format | Article |
| id | doaj.art-8f37c19b21bd4533862290fb8edd18d0 |
| institution | Directory Open Access Journal |
| issn | 2312-0541 |
| language | English |
| last_indexed | 2024-04-12T17:16:04Z |
| publishDate | 2018-11-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj.art-8f37c19b21bd4533862290fb8edd18d02022-12-22T03:23:39ZengEuropean Respiratory SocietyERJ Open Research2312-05412018-11-014410.1183/23120541.00031-201800031-2018Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPDKatherine J. Baines0Thomas K. Wright1Peter G. Gibson2Heather Powell3Philip M. Hansbro4Jodie L. Simpson5 Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia Dept of Respiratory and Sleep Medicine, Hunter New England Area Health Service, Newcastle, Australia Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia 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.http://openres.ersjournals.com/content/4/4/00031-2018.full |
| spellingShingle | Katherine J. Baines Thomas K. Wright Peter G. Gibson Heather Powell Philip M. Hansbro Jodie L. Simpson Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD ERJ Open Research |
| title | Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD |
| title_full | Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD |
| title_fullStr | Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD |
| title_full_unstemmed | Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD |
| title_short | Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD |
| title_sort | azithromycin treatment modifies airway and blood gene expression networks in neutrophilic copd |
| url | http://openres.ersjournals.com/content/4/4/00031-2018.full |
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