Bedi, P. et al (2018) Blood Neutrophils are Reprogrammed in Bronchiectasis. Am J Respir Crit Care Med. [Epub ahead of print]

Bedi, P. et al (2018) Blood Neutrophils are Reprogrammed in Bronchiectasis.

P. Bedi, D.J. Davidson, B. J. McHugh, A.G. Rossi, A. T. Hill

Am J Respir Crit Care Med. [Epub ahead of print]   Link to paper

Davidson lab supported by funding from: MRC

ABSTRACT
Introduction Excessive neutrophilic airways inflammation is the central feature of bronchiectasis, but little is known about neutrophils in bronchiectasis. The aim of this study was to assess blood neutrophil phenotype in bronchiectasis patients both whilst stable and during exacerbations. Methods In the clinically-stable arm of this study were 8-healthy volunteers, 8-mild and 8-severe bronchiectasis. In addition, 6-severe bronchiectasis patients were compared with 6-community-acquired pneumonia patients at the start and end of an exacerbation. We assessed neutrophils for spontaneous apoptosis, cell surface marker expression, degranulation, reactive oxygen species generation, phagocytosis and killing of Pseudomonas aeruginosa (PAO1). In addition, blood neutrophil function was compared to airway neutrophil function in bronchiectasis. Results In stable bronchiectasis, compared to healthy volunteers, blood neutrophils had: significantly prolonged viability; delayed apoptosis; increased CD62L shedding; upregulated CD11b expression; increased myeloperoxidase release; impaired neutrophil phagocytosis and killing of PAO1. Bronchiectatic airway neutrophils had significantly lower bacterial phagocytosis and killing, than their matched autologous blood neutrophils. Both blood and airway neutrophil phagocytosis and killing was impaired at the start of an exacerbation and improved following antibiotic treatment. In pneumonia, there was a significant improvement in phagocytosis and killing after treatment with antibiotics. During infections, there was no difference in phagocytosis, but there was significantly increased bacterial killing at the start and end of infection in pneumonia compared to bronchiectasis exacerbations. Conclusion In bronchiectasis stable state, peripheral blood neutrophils are reprogrammed and have prolonged survival.This impairs their functional ability of bacterial phagocytosis and killing, thereby perpetuating the vicious circle in bronchiectasis.
PMID: 29733693
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