High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis
Introduction COPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations are also heterogeneous in neutrophilic or eosinophilic inflammatory responses. A noninvasive peripheral biomarker of COPD exacerbations characterised by bacterial/neutr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
European Respiratory Society
2021-08-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/7/3/00836-2020.full |
| _version_ | 1818986818998108160 |
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| author | Arindam Chakrabarti Jordan S. Mar David F. Choy Yi Cao Nisha Rathore Xiaoying Yang Gaik W. Tew Olga Li Prescott G. Woodruff Christopher E. Brightling Michele Grimbaldeston Stephanie A. Christenson Mona Bafadhel Carrie M. Rosenberger |
| author_facet | Arindam Chakrabarti Jordan S. Mar David F. Choy Yi Cao Nisha Rathore Xiaoying Yang Gaik W. Tew Olga Li Prescott G. Woodruff Christopher E. Brightling Michele Grimbaldeston Stephanie A. Christenson Mona Bafadhel Carrie M. Rosenberger |
| author_sort | Arindam Chakrabarti |
| collection | DOAJ |
| description | Introduction
COPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations are also heterogeneous in neutrophilic or eosinophilic inflammatory responses. A noninvasive peripheral biomarker of COPD exacerbations characterised by bacterial/neutrophilic inflammation is lacking. Granulocyte-colony stimulating factor (G-CSF) is a key cytokine elevated during bacterial infection and mediates survival, proliferation, differentiation and function of neutrophils.
Objective
We hypothesised that high peripheral G-CSF would be indicative of COPD exacerbations with a neutrophilic and bacterial phenotype associated with microbial dysbiosis.
Methods
Serum G-CSF was measured during hospitalised exacerbation (day 0 or D0) and after 30 days of recovery (Day30 or D30) in 37 subjects. In a second cohort, serum and sputum cytokines were measured in 59 COPD patients during stable disease, at exacerbation, and at 2-weeks and 6-weeks following exacerbation.
Results
Serum G-CSF was increased during exacerbation in a subset of patients. These exacerbations were enriched for bacterial but not viral or type-2 biologies. The median serum G-CSF level was 1.6-fold higher in bacterial exacerbation compared to nonbacterial exacerbation (22 pg·mL−1 versus 13 pg·mL−1, p=0.0007). Serum G-CSF classified bacterial exacerbations with an area under the curve (AUC) for the receiver operating characteristic (ROC) curve equal to 0.76. Exacerbations with a two-fold or greater increase in serum G-CSF were characterised by neutrophilic inflammation, with increased sputum and blood neutrophils, and high sputum interleukin (IL)-1β, IL-6 and serum amyloid A1 (SAA1) levels. These exacerbations were preceded by dysbiosis, with decreased microbiome diversity and enrichment of respiratory pathogens such as Haemophilus and Moraxella. Furthermore, serum G-CSF at exacerbation classified neutrophilic-dysbiotic exacerbations (AUC for the ROC curve equal to 0.75).
Conclusions
High serum G-CSF enriches for COPD exacerbations characterised by neutrophilic inflammation with underlying bacterial dysbiosis. |
| first_indexed | 2024-12-20T18:56:51Z |
| format | Article |
| id | doaj.art-692862264ef245069cba5c9438c1380c |
| institution | Directory Open Access Journal |
| issn | 2312-0541 |
| language | English |
| last_indexed | 2024-12-20T18:56:51Z |
| publishDate | 2021-08-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj.art-692862264ef245069cba5c9438c1380c2022-12-21T19:29:30ZengEuropean Respiratory SocietyERJ Open Research2312-05412021-08-017310.1183/23120541.00836-202000836-2020High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosisArindam Chakrabarti0Jordan S. Mar1David F. Choy2Yi Cao3Nisha Rathore4Xiaoying Yang5Gaik W. Tew6Olga Li7Prescott G. Woodruff8Christopher E. Brightling9Michele Grimbaldeston10Stephanie A. Christenson11Mona Bafadhel12Carrie M. Rosenberger13 Biomarker Discovery OMNI, Genentech Inc., South San Francisco, CA, USA Biomarker Discovery OMNI, Genentech Inc., South San Francisco, CA, USA Biomarker Discovery OMNI, Genentech Inc., South San Francisco, CA, USA Bioinformatics, Genentech Inc., South San Francisco, CA, USA Biomarker Discovery OMNI, Genentech Inc., South San Francisco, CA, USA Biostatistics, Genentech Inc., South San Francisco, CA, USA OMNI Biomarker Development, Genentech Inc., South San Francisco, CA, USA OMNI Biomarker Development, Genentech Inc., South San Francisco, CA, USA Dept of Medicine, UCSF, San Francisco, CA, USA Dept of Respiratory Sciences, University of Leicester, Leicester, UK OMNI Biomarker Development, Genentech Inc., South San Francisco, CA, USA Dept of Medicine, UCSF, San Francisco, CA, USA Nuffield Dept of Medicine, University of Oxford, Oxford, UK Biomarker Discovery OMNI, Genentech Inc., South San Francisco, CA, USA Introduction COPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations are also heterogeneous in neutrophilic or eosinophilic inflammatory responses. A noninvasive peripheral biomarker of COPD exacerbations characterised by bacterial/neutrophilic inflammation is lacking. Granulocyte-colony stimulating factor (G-CSF) is a key cytokine elevated during bacterial infection and mediates survival, proliferation, differentiation and function of neutrophils. Objective We hypothesised that high peripheral G-CSF would be indicative of COPD exacerbations with a neutrophilic and bacterial phenotype associated with microbial dysbiosis. Methods Serum G-CSF was measured during hospitalised exacerbation (day 0 or D0) and after 30 days of recovery (Day30 or D30) in 37 subjects. In a second cohort, serum and sputum cytokines were measured in 59 COPD patients during stable disease, at exacerbation, and at 2-weeks and 6-weeks following exacerbation. Results Serum G-CSF was increased during exacerbation in a subset of patients. These exacerbations were enriched for bacterial but not viral or type-2 biologies. The median serum G-CSF level was 1.6-fold higher in bacterial exacerbation compared to nonbacterial exacerbation (22 pg·mL−1 versus 13 pg·mL−1, p=0.0007). Serum G-CSF classified bacterial exacerbations with an area under the curve (AUC) for the receiver operating characteristic (ROC) curve equal to 0.76. Exacerbations with a two-fold or greater increase in serum G-CSF were characterised by neutrophilic inflammation, with increased sputum and blood neutrophils, and high sputum interleukin (IL)-1β, IL-6 and serum amyloid A1 (SAA1) levels. These exacerbations were preceded by dysbiosis, with decreased microbiome diversity and enrichment of respiratory pathogens such as Haemophilus and Moraxella. Furthermore, serum G-CSF at exacerbation classified neutrophilic-dysbiotic exacerbations (AUC for the ROC curve equal to 0.75). Conclusions High serum G-CSF enriches for COPD exacerbations characterised by neutrophilic inflammation with underlying bacterial dysbiosis.http://openres.ersjournals.com/content/7/3/00836-2020.full |
| spellingShingle | Arindam Chakrabarti Jordan S. Mar David F. Choy Yi Cao Nisha Rathore Xiaoying Yang Gaik W. Tew Olga Li Prescott G. Woodruff Christopher E. Brightling Michele Grimbaldeston Stephanie A. Christenson Mona Bafadhel Carrie M. Rosenberger High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis ERJ Open Research |
| title | High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis |
| title_full | High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis |
| title_fullStr | High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis |
| title_full_unstemmed | High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis |
| title_short | High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis |
| title_sort | high serum granulocyte colony stimulating factor characterises neutrophilic copd exacerbations associated with dysbiosis |
| url | http://openres.ersjournals.com/content/7/3/00836-2020.full |
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