Relationship of monocyte-derived macrophage phagocytosis to exacerbation susceptibility in stable COPD

Defective macrophage phagocytosis has been demonstrated in both alveolar and monocyte-derived macrophages (MDMs) from COPD patients, contributing to the persistence of airway bacteria. We hypothesised that MDM phagocytic capacity may relate to exacerbation susceptibility and would remain stable over time. MDMs were cultured from whole blood collected from 70 stable COPD patients, and subsequently repeated in 30 patients. Phagocytosis of three prey; fluorescently-labelled inert beads, or heat-killed Haemophilus influenzae (HI) & Streptococcus pneumoniae (SP) was measured. The mean age was 72.1 years (SD9.2), FEV 1 predicted 55.4% (17.9) and 33% current smokers. Phagocytosis of HI, but not SP or beads, was significantly less with increasing exacerbation frequency (p 1 %predicted, smoking history or ICS use (all p>0.05). In the 30 patients with repeated MDMs after a median time of 9 (6-13) months, there was no significant change in phagocytic capacity of any prey (p>0.05, Figure 1B). Defective phagocytosis of HI, but not SP or beads, is associated with higher exacerbation frequency in stable COPD, although the phagocytic capacity of any prey remained stable over time. Further work is needed to determine whether improvement in phagocytic capacity can reduce future risk of exacerbations.