Serum G-CSF is a Non-Invasive Biomarker Classifying Bacterial/neutrophilic COPD Exacerbations

Introduction: COPD exacerbations are heterogeneous and often triggered by bacterial or viral infection or type-2 inflammation. A non-invasive peripheral biomarker that can be routinely measured to characterize a bacterial/neutrophilic COPD exacerbation is lacking. COPD airways are characterized by heterogeneous granulocytic inflammation. G-CSF is one of the key cytokines elevated during infection and mediates survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils. Objective: We hypothesized that peripheral G-CSF would be a biomarker of a neutrophilic COPD phenotype and would enrich for bacterial/neutrophilic exacerbations. Methods: Serum and sputum cytokines were measured for 54 COPD subjects during stable disease, at exacerbation, 2- and 6-weeks following exacerbations. Results: 1) High G-CSF levels during exacerbation is associated with higher frequency of bacterial infection. The geometric mean of G-CSF levels for bacterial exacerbation was higher (1.8-fold) than non-bacterial exacerbation [24.2 pg/ml (18.6-32.2) to 13.2 pg/ml (11.3-15.8), 95% CI; p = 0.0007] with an area under the ROC curve of 0.76. The G-CSF fold-change (stable to exacerbation visit) during bacterial exacerbation were also significantly higher than non-bacterial exacerbation [1.9-fold (1.4-2.6) vs. 1.2-fold (1.0-1.4), 95% CI; p = 0.04), 2) Elevated serum G-CSF at exacerbation reflects lung neutrophilic inflammation. Conclusions: In our current study we found that serum G-CSF is a potential peripheral biomarker to classify COPD exacerbations of bacterial origin associated with neutrophilic inflammation.