Comparison of fluticasone propionate and budesonide on phagocytosis of common respiratory pathogens in COPD patients

Background: Inhaled corticosteroids are recommended for COPD patients with FEV 1 ≤ 50% predicted, experiencing ≥2 exacerbations in 12 months. However, post-hoc analysis of the TORCH study revealed an increased risk of pneumonia of 50% in patients taking inhaled fluticasone propionate (FP) (ERJ 2009;34:641). This contrasts with a meta-analysis of patients taking budesonide (BUD) where there was no increased risk of pneumonia (Lancet 2009;374:712). The reason for this discrepancy is unclear, however, we hypothesise that the particulate nature of FP, due to high lipophilicity and low water solubility, leads to its uptake by phagocytes resulting in impaired function. Methods: Neutrophils and monocytes were isolated from the blood of COPD patients (n=10). Monocyte-derived macrophages (MDM) were generated from monocytes by 12d culture in media containing GM-CSF. All cells were incubated with steroid for 1h prior to phagocytosis assays with fluorescently-labelled polystyrene beads, Haemophilus influenzae (HI) or Streptococcus pneumoniae (SP). Results: BUD (1μM) increased MDM phagocytosis of beads by 17% (p -10 -10 -6 M) significantly (p Conclusions: FP did not reduce phagocytic function of either MDM or neutrophils. BUD improved neutrophil phagocytosis of HI, which may explain differences in pneumonia incidence between FP and BUD in COPD patients.