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

Lung. 2016 Dec;194(6):881-887. doi: 10.1007/s00408-016-9930-z. Epub 2016 Aug 16.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: This study is the first to report aberrant receptor-mediated blood neutrophil function in the frequent exacerbator of COPD.

Keywords: Chronic obstructive pulmonary disease; Elastase; Granulocyte; Polymorphonuclear leukocytes; Reactive oxygen species.

MeSH terms

  • Aged
  • Case-Control Studies
  • Cell Degranulation*
  • Disease Progression*
  • Female
  • Humans
  • Male
  • Middle Aged
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / physiology*
  • Proof of Concept Study
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Respiratory Burst / drug effects
  • Symptom Flare Up*
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • phorbolol myristate acetate
  • N-Formylmethionine Leucyl-Phenylalanine
  • Tetradecanoylphorbol Acetate