Sputum neutrophils in cystic fibrosis patients display a reduced respiratory burst

Abstract

Few data exist on the functional activity of airway neutrophils in the milieu of the cystic fibrosis (CF) lung. We assessed reactive oxygen species (ROS) production by sputum neutrophils and the relationship to neutrophil viability. Identical assessments were made on peripheral blood neutrophils from CF patients. ROS production in sputum neutrophils was assessed in 31 CF patients at varying phases of clinical disease using flow cytometry. Twenty patients provided blood samples (including 16 who also provided a matched sputum sample). Neutrophil viability was determined using dual annexin V (apoptosis) and propidium iodide (necrosis) staining. Comparative peripheral blood data were obtained from 7 healthy controls. ROS production was reduced in sputum compared to blood neutrophils and they demonstrated a higher level of necrosis. Subpopulations of neutrophils with different ROS production capacity were apparent in peripheral blood. Lung function was positively associated with both the proportion of blood neutrophils demonstrating increased ROS production and the proportion of apoptotic sputum neutrophils. CF airway neutrophils display functional exhaustion. Healthier lungs in CF appear to be associated with subpopulations of blood neutrophils with increased oxidative burst capacity and evidence for increased neutrophil apoptosis within the airway.