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P184 Macrophage phagocytosis in COPD patients at exacerbation compared to stable state
  1. R Singh1,
  2. K Such2,
  3. BS Kowlessar1,
  4. ARC Patel1,
  5. AJ Mackay1,
  6. SE Brill1,
  7. JP Allinson1,
  8. GC Donaldson1,
  9. PJ Barnes2,
  10. JA Wedzicha1,
  11. LE Donnelly2
  1. 1Centre for Respiratory Medicine, UCL Medical School, London, UK
  2. 2Airway Disease Section, NHLI, Imperial College, London, UK

Abstract

Introduction COPD exacerbations are clinically important events, commonly triggered by bacterial infection. Defective phagocytosis of potentially pathogenic microorganisms (PPMs) in stable COPD has been demonstrated in both alveolar and monocyte-derived macrophages (MDMs). We hypothesised that phagocytosis may be suppressed further during an acute COPD exacerbation and relate to bacterial aetiology of the exacerbation.

Methods Whole blood was collected from patients in the London COPD cohort at both stable state and at exacerbation, as defined by prospectively completed daily symptom diary cards (Seemungal et al ., 1998). Monocytes were isolated and cultured with GM-CSF (2ng/ml) for 12 days to generate MDMs. MDM phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae (HI) and Streptococcus pneumoniae (SP) was measured by fluorimetry. Diary card data was used to determine prodromal symptoms, exacerbation duration and exacerbation symptom intensity. Sputa collected at exacerbation were cultured for PPMs.

Results MDMs were cultured from 13 COPD patients at paired stable and exacerbation states. 54% were male, mean age 72.8 years (SD 6.2), FEV1 predicted 55.7% (20.5) and 38% current smokers. The median time between stable and exacerbation states was 147 days [IQR 75–212].

Two distinct patterns of change in phagocytic ability were seen between the stable and exacerbation state. Eight patients significantly decreased their phagocytic capacity compared to stable state for beads, HI and SP (p = 0.004, p = 0.008 and p = 0.020 respectively, Figure 1A). Five of these eight patients (63%) had a PPM isolated in their exacerbation sputum sample. Five of 13 patients increased phagocytosis at exacerbation (Figure 1B), but only SP reached statistical significance (p = 0.031). Only one of these five (20%) had a PPM in their exacerbation sputum sample.

There was no significant difference between the presence of prodromal symptoms, exacerbation duration or symptom intensity between the two patterns.

Conclusion Phagocytosis of bacteria is suppressed further during some COPD exacerbations. This may contribute to bacterial aetiology of these exacerbations. Phagocytosis appears partially more effective in other exacerbations. Further work is needed to understand these apparently dichotomous changes and their impact on clinical outcomes.

Abstract P184 Figure 1(A).

Increased MDM Phagocytosis at exacerbation, n = 8; (B) Decreased MDM phagocytosis at exacerbation, n = 5.

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