Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study.

Abstract

PurposeThe underlying biological mechanisms of the frequent exacerbator phenotype of COPD remain unclear. We compared systemic neutrophil function in COPD patients with or without frequent exacerbations.MethodsWhole blood from COPD frequent exacerbators (defined as ≥2 moderate–severe exacerbations in the previous 2 years) and non-exacerbators (no exacerbations in the preceding 2 years) was assayed for neutrophil function. Neutrophil function in healthy ex-smoking volunteers was also measured as a control (reference) group.ResultsA total of 52 subjects were included in this study: 26 frequent exacerbators, 18 non-exacerbators and 8 healthy controls. COPD frequent exacerbators had blunted blood neutrophil fMLP-stimulated oxidative burst compared to both non-exacerbators (p < 0.01) and healthy controls (p < 0.001). There were no differences between COPD frequent exacerbators and non-exacerbators in blood neutrophil PMA-stimulated oxidative burst, but both COPD groups had reduced responses compared to healthy controls (p < 0.001). Bacterial-stimulated neutrophil degranulation was greater in frequent exacerbators than non-exacerbators (p < 0.05).ConclusionThis study is the first to report aberrant receptor-mediated blood neutrophil function in the frequent exacerbator of COPD.