Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept StudyReportar como inadecuado




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Lung

, Volume 194, Issue 6, pp 881–887

First Online: 16 August 2016Received: 09 February 2016Accepted: 07 August 2016

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.

KeywordsChronic obstructive pulmonary disease Elastase Granulocyte Polymorphonuclear leukocytes Reactive oxygen species Abbreviationsα1-PIAlpha 1-proteinase inhibitor

CLChemiluminescence

eCOExhaled carbon monoxide

fMLPFormyl-methionyl-leucyl-phenylalanine

HBSSHank’s balanced salt solution

NADPHNicotinamide adenine dinucleotide phosphate

NENeutrophil elastase

PMAPhorbol-12-myristate-13-acetate

ROSReactive oxygen species

RLURelative light units

TLRToll-like receptor

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Autor: Arwel Wyn Jones - Richard Robinson - Peer Mohamed - Glen Davison - Hassan Jaysen Izzat - Keir Edward Lewis

Fuente: https://link.springer.com/article/10.1007/s00408-016-9930-z







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