title: Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study.
abstract: The 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.
  
  
  
  Whole 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.
  
  
  
  A 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).
  
  
  
  This study is the first to report aberrant receptor-mediated blood neutrophil function in the frequent exacerbator of COPD.
authors.affiliation: Lincoln Institute for Health, University of Lincoln, Brayford Pool, Lincoln, LN6 7TS, UK. arjones@lincoln.ac.uk.
authors.forename: Arwel Wyn
authors.initials: AW
authors.lastname: Jones
authors.affiliation: Department of Respiratory Medicine, Prince Philip Hospital, Hywel Dda University Health Board, Llanelli, SA14 8QF, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Robinson
authors.affiliation: Department of Respiratory Medicine, Prince Philip Hospital, Hywel Dda University Health Board, Llanelli, SA14 8QF, UK.
authors.forename: Peer
authors.initials: P
authors.lastname: Mohamed
authors.affiliation: School of Sport and Exercise Sciences, University of Kent, Medway Campus, Chatham Maritime, ME4 4AG, UK.
authors.forename: Glen
authors.initials: G
authors.lastname: Davison
authors.affiliation: Department of Respiratory Medicine, Prince Philip Hospital, Hywel Dda University Health Board, Llanelli, SA14 8QF, UK.
authors.forename: Hassan Jaysen
authors.initials: HJ
authors.lastname: Izzat
authors.affiliation: Department of Respiratory Medicine, Prince Philip Hospital, Hywel Dda University Health Board, Llanelli, SA14 8QF, UK.|College of Medicine, Swansea University, Swansea, SA2 8PP, UK.
authors.forename: Keir Edward
authors.initials: KE
authors.lastname: Lewis
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015550:Cell Degranulation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D000075082:Proof of Concept Study; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D016897:Respiratory Burst / Q000187:drug effects; D000067251:Symptom Flare Up; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C016658:phorbolol myristate acetate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate
keywords: Chronic obstructive pulmonary disease; Elastase; Granulocyte; Polymorphonuclear leukocytes; Reactive oxygen species