PT  - JOURNAL ARTICLE
AU  - Arindam Chakrabarti
AU  - Jordan S. Mar
AU  - David F. Choy
AU  - Yi Cao
AU  - Nisha Rathore
AU  - Xiaoying Yang
AU  - Gaik W. Tew
AU  - Olga Li
AU  - Prescott G. Woodruff
AU  - Christopher E. Brightling
AU  - Michele Grimbaldeston
AU  - Stephanie A. Christenson
AU  - Mona Bafadhel
AU  - Carrie M. Rosenberger
TI  - High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis
AID  - 10.1183/23120541.00836-2020
DP  - 2021 Jul 01
TA  - ERJ Open Research
PG  - 00836-2020
VI  - 7
IP  - 3
4099  - http://openres.ersjournals.com/content/7/3/00836-2020.short
4100  - http://openres.ersjournals.com/content/7/3/00836-2020.full
SO  - erjor2021 Jul 01; 7
AB  - 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.Noninvasive biomarkers to characterise #AECOPD subtypes are limited. High serum G-CSF enriches for COPD exacerbations associated with bacterial infection and neutrophilic inflammation preceded by lung microbial dysbiosis. https://bit.ly/3rck3M6