COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils.
Eltboli O., Bafadhel M., Hollins F., Wright A., Hargadon B., Kulkarni N., Brightling C.
BACKGROUND: Eosinophilic airway inflammation is observed in 10-30% of COPD subjects. Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown. METHODS: We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥ 3%/year). Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls. RESULTS: There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n=10), B-high red hue, high sputum eosinophils (n=16), C-low red hue, low sputum eosinophils (n=19) and D- high red hue, low sputum eosinophils (n=58). Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p=0.01). The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p=0.02). Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p=0.028); was most marked in group A (71 [70 to 84]%; p=0.0295) and was inversely correlated with exacerbation frequency (r=-0.63; p=0.006). CONCLUSIONS: Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations.