Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease
Katherine J Baines,1,2 Juan-juan Fu,3 Vanessa M McDonald,1,2 Peter G Gibson1,2 1Faculty of Health and Medicine, Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, 2Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambto...
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doaj-8ef277a669424c2abd22b5f1f9b0761c2020-11-24T21:25:17ZengDove Medical PressInternational Journal of COPD1178-20052017-02-01Volume 1254155031203Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway diseaseBaines KJFu JJMcDonald VMGibson PGKatherine J Baines,1,2 Juan-juan Fu,3 Vanessa M McDonald,1,2 Peter G Gibson1,2 1Faculty of Health and Medicine, Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, 2Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW, Australia; 3Respiratory Group, Department of Integrated Traditional Chinese and West Medicine, West China Hospital, Sichuan University, People’s Republic of China Background: Exacerbations of asthma and COPD are a major cause of morbidity and mortality and are responsible for significant health care costs. This study further investigates interleukin (IL)-1 pathway activation and its relationship with exacerbations of asthma and COPD. Methods: In this prospective cohort study, 95 participants with stable asthma (n=35) or COPD (n=60) were recruited and exacerbations recorded over the following 12 months. Gene expressions of IL-1 pathway biomarkers, including the IL-1 receptors (IL1R1, IL1R2, and IL1RN), and signaling molecules (IRAK2, IRAK3, and PELI1), were measured in sputum using real-time quantitative polymerase chain reaction. Mediators were compared between the frequent (≥2 exacerbations in the 12 months) and infrequent exacerbators, and the predictive relationships investigated using receiver operating characteristic curves and area under the curve (AUC) values. Results: Of the 95 participants, 89 completed the exacerbation follow-up, where 30 participants (n=22 COPD, n=8 asthma) had two or more exacerbations. At the baseline visit, expressions of IRAK2, IRAK3, PELI1, and IL1R1 were elevated in participants with frequent exacerbations of both asthma and COPD combined and separately. In the combined population, sputum gene expression of IRAK3 (AUC=75.4%; P<0.001) was the best predictor of future frequent exacerbations, followed by IL1R1 (AUC=72.8%; P<0.001), PELI1 (AUC=71.2%; P<0.001), and IRAK2 (AUC=68.6; P=0.004). High IL-1 pathway gene expression was associated with frequent prior year exacerbations and correlated with the number and severity of exacerbations. Conclusion: The upregulation of IL-1 pathway mediators is associated with frequent exacerbations of obstructive airway disease. Further studies should investigate these mediators as both potential diagnostic biomarkers predicting at-risk patients and novel treatment targets. Keywords: COPD, asthma, exacerbations, interleukin-1https://www.dovepress.com/airway-gene-expression-of-il-1-pathway-mediators-predicts-exacerbation-peer-reviewed-article-COPDCOPDasthmaexacerbationsinterleukin-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Baines KJ Fu JJ McDonald VM Gibson PG |
spellingShingle |
Baines KJ Fu JJ McDonald VM Gibson PG Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease International Journal of COPD COPD asthma exacerbations interleukin-1 |
author_facet |
Baines KJ Fu JJ McDonald VM Gibson PG |
author_sort |
Baines KJ |
title |
Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease |
title_short |
Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease |
title_full |
Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease |
title_fullStr |
Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease |
title_full_unstemmed |
Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease |
title_sort |
airway gene expression of il-1 pathway mediators predicts exacerbation risk in obstructive airway disease |
publisher |
Dove Medical Press |
series |
International Journal of COPD |
issn |
1178-2005 |
publishDate |
2017-02-01 |
description |
Katherine J Baines,1,2 Juan-juan Fu,3 Vanessa M McDonald,1,2 Peter G Gibson1,2 1Faculty of Health and Medicine, Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, 2Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW, Australia; 3Respiratory Group, Department of Integrated Traditional Chinese and West Medicine, West China Hospital, Sichuan University, People’s Republic of China Background: Exacerbations of asthma and COPD are a major cause of morbidity and mortality and are responsible for significant health care costs. This study further investigates interleukin (IL)-1 pathway activation and its relationship with exacerbations of asthma and COPD. Methods: In this prospective cohort study, 95 participants with stable asthma (n=35) or COPD (n=60) were recruited and exacerbations recorded over the following 12 months. Gene expressions of IL-1 pathway biomarkers, including the IL-1 receptors (IL1R1, IL1R2, and IL1RN), and signaling molecules (IRAK2, IRAK3, and PELI1), were measured in sputum using real-time quantitative polymerase chain reaction. Mediators were compared between the frequent (≥2 exacerbations in the 12 months) and infrequent exacerbators, and the predictive relationships investigated using receiver operating characteristic curves and area under the curve (AUC) values. Results: Of the 95 participants, 89 completed the exacerbation follow-up, where 30 participants (n=22 COPD, n=8 asthma) had two or more exacerbations. At the baseline visit, expressions of IRAK2, IRAK3, PELI1, and IL1R1 were elevated in participants with frequent exacerbations of both asthma and COPD combined and separately. In the combined population, sputum gene expression of IRAK3 (AUC=75.4%; P<0.001) was the best predictor of future frequent exacerbations, followed by IL1R1 (AUC=72.8%; P<0.001), PELI1 (AUC=71.2%; P<0.001), and IRAK2 (AUC=68.6; P=0.004). High IL-1 pathway gene expression was associated with frequent prior year exacerbations and correlated with the number and severity of exacerbations. Conclusion: The upregulation of IL-1 pathway mediators is associated with frequent exacerbations of obstructive airway disease. Further studies should investigate these mediators as both potential diagnostic biomarkers predicting at-risk patients and novel treatment targets. Keywords: COPD, asthma, exacerbations, interleukin-1 |
topic |
COPD asthma exacerbations interleukin-1 |
url |
https://www.dovepress.com/airway-gene-expression-of-il-1-pathway-mediators-predicts-exacerbation-peer-reviewed-article-COPD |
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