High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis. Issue 3 (2nd August 2021)

• Record Type: Journal Article
• Authors: Chakrabarti, Arindam; Mar, Jordan S.; Choy, David F.; Cao, Yi; Rathore, Nisha; Yang, Xiaoying; Tew, Gaik W.; Li, Olga; Woodruff, Prescott G.; Brightling, Christopher E.; Grimbaldeston, Michele; Christenson, Stephanie A.; Bafadhel, Mona; Rosenberger, Carrie M.
• Is Part Of: ERJ open research. Volume 7:Issue 3(2021)
• Publication Date: 2021-08-02
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; Respiration; Respiratory organs -- Diseases; Respiratory organs -- Diseases -- Treatment; Respiratory Tract Diseases; Electronic journals; Fulltext; Internet Resources; Periodicals; Periodical; 616.2005
• DOI: 10.1183/23120541.00836-2020
• Languages: English
• ISSNs: 2312-0541

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. 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