- Title
- A sputum 6 gene expression signature predicts inflammatory phenotypes and future exacerbations of COPD
- Creator
- Baines, Katherine J.; Negewo, Netsanet A.; Gibson, Peter G.; Fu, Juan-Juan; Simpson, Jodie L.; Wark, Peter A. B.; Fricker, Michael; McDonald, Vanessa M.
- Relation
- International Journal of Chronic Obstructive Pulmonary Disease Vol. 15, p. 1577-1590
- Publisher Link
- http://dx.doi.org/10.2147/COPD.S245519
- Publisher
- Dove Medical Press
- Resource Type
- journal article
- Date
- 2020
- Description
- Background: The 6 gene expression signature (6GS) predicts inflammatory phenotype, exacerbation risk, and corticosteroid responsiveness in asthma. In COPD, patterns of airway inflammation are similar, suggesting the 6GS may be useful. This study determines the diagnostic and prognostic ability of 6GS in predicting inflammatory phenotypes and exacerbation risk in COPD. Methods: We performed 2 studies: a cross-sectional phenotype prediction study in stable COPD (total N=132; n=34 eosinophilic (E)-COPD, n=42 neutrophilic (N)-COPD, n=39 paucigranulocytic (PG)-COPD, n=17 mixed-granulocytic (MG)-COPD) that assessed 6GS ability to discriminate phenotypes (eosinophilia≥ 3%; neutrophilia≥ 61%); and a prospective cohort study (total n=54, n=8 E-COPD; n=18 N-COPD; n=20 PG-COPD; n=8 MG-COPD, n=21 exacerbation prone (≥ 2/year)) that investigated phenotype and exacerbation prediction utility. 6GS was measured by qPCR and evaluated using multiple logistic regression and area under the curve (AUC). Short-term reproducibility (intra-class correlation) and phenotyping method agreement (κ statistic) were assessed. Results: In the phenotype prediction study, 6GS could accurately identify and discriminate patients with E-COPD from N-COPD (AUC=96.4%; p< 0.0001), PG-COPD (AUC=88.2%; p< 0.0001) or MG-COPD (AUC=86.2%; p=0.0001), as well as N-COPD from PG-COPD (AUC=83.6%; p< 0.0001) or MG-COPD (AUC=87.4%; p< 0.0001) and was reproducible. In the prospective cohort study, 6GS had substantial agreement for neutrophilic inflammation (82%, κ=0.63, p< 0.001) and moderate agreement for eosinophilic inflammation (78%, κ=0.42, p< 0.001). 6GS could significantly discriminate exacerbation prone patients (AUC=77.2%; p=0.034). Higher IL1B levels were associated with poorer lung function and increased COPD severity. Conclusion: 6GS can significantly and reproducibly discriminate COPD inflammatory phenotypes and predict exacerbation prone patients and may become a useful molecular diagnostic tool assisting COPD management.
- Subject
- COPD; airway markers; inflammation; molecular biology; eosinophil
- Identifier
- http://hdl.handle.net/1959.13/1426187
- Identifier
- uon:38377
- Identifier
- ISSN:1178-2005
- Rights
- © 2020 Baines et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
- Language
- eng
- Full Text
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