S72 Investigating the neutrophil phenotype in COPD with common co-morbidities

Introduction Neutrophils are implicated in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Multi-morbidity is increasingly common and COPD is often present with cardiovascular disease (CVD) and Type-2 Diabetes Mellitus (T2D). Studies have shown altered neutrophil function in chronic inflammatory conditions including COPD, CVD and T2D. We hypothesised that these conditions may cause a shift in neutrophil phenotype and we aimed to assess the surface expression of functional markers, in patients with COPD, stratified based on their co-morbidities of CVD and T2D, focusing on activated, immature, or senescent surface expression. Methods All samples were obtained with informed consent. Neutrophils from 15 healthy young donors (median 27±8 years), 15 age-matched controls (median 72±3.5 years), 45 patients with stable COPD (15 with both a CVD and T2D, median 70±7.75 years; 15 with a CVD, median 72±1.75 years; 15 with T2D, median 73±4 years and 15 with neither a CVD or T2D, median 71±4 years) and 15 patients with exacerbations of COPD (AECOPD, median 73±7) were isolated from whole blood and incubated with primary antibodies prior to analysis by flow cytometry. Patients with stable COPD were then stratified based on previous clinical diagnoses of T2D or CVD. Results There were no differences in activation markers (CD11b, CD66b and CD62L) on neutrophils between patients with COPD and healthy controls. There was a trend towards a reduction in the surface expression of the chemokine receptor for CXCL8, CXCR2 (mean±sd 3989±615 healthy age-matched vs 3596±561, p=0.08). This reduction in CXCR2 expression was significant when assessing patients with COPD and CVD (median 3216±600, p=0.005 vs healthy age-matched control) or presenting with an acute exacerbation of COPD (2839±791, p=0.005 vs stable COPD). Changes in CXCR2 expression were not mirrored by increases in CXCR4 expression, as previously reported in neutrophil senescence (Yildirim et al., 2005). Conclusion Differences in neutrophil function in patients with COPD, CVD and T2D do not appear to be due to distinct changes in cell phenotype. COPD with CVD and AECOPD are associated with a reduction in CXCR2 expression, but there is substantial heterogeneity within this patient population. Reference Yildirim, S, et al. ( 2005) Blood, 106(11).