High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis.

Abstract

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.

• Authors: 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
• Journal: ERJ open research (ERJ Open Res) Vol. 7 Issue 3 (Jul 2021) ISSN: 2312-0541 [Print] England
• PMID: 34350278 (Publication Type: Journal Article)
• Copyright: Copyright ©The authors 2021.