S70 Inaccurate neutrophil migration in symptomatic smokers without chronic obstructive pulmonary disease

Introduction Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality worldwide. Not all smokers develop COPD and currently we cannot predict those most at risk although chronic bronchitis (CB) is associated with worse outcomes and may be an indicator of risk. Neutrophil dysfunction has been implicated in COPD pathogenesis, but it is unclear if this is causative or reflects a secondary response to COPD itself. We hypothesised that CB would identify individuals most at risk of COPD and that these individuals would have impaired neutrophil functions, prior to the progression to COPD. Methods As part of the BLF Early COPD Consortium, current smokers (CS) aged 30–45, with >10-pack year history but with normal spirometry, were matched by age to patients with COPD and healthy never smokers (NS). CS were divided into asymptomatic smokers (AS) and those with CB. Peripheral neutrophils were isolated from whole blood and migrated in gradients of interleukin-8(IL8) or vehicle control, in an Insall chemotaxis chamber. Migration was assessed for speed and accuracy in real-time using video capture microscopy. Results Neutrophils from patients with COPD migrated with significantly increased speed compared with all other groups (mean ± SD). COPD 5.62µm/min ±0.25; NS 4.72µm/min ±0.19, p=0.02; AS 4.37µm/min ±0.30, p=0.0005; CB 4.24µm/min ±0.21, p=0.005). COPD neutrophils migrated with reduced accuracy compared to NS and AS (COPD: 0.57µm/min ±0.13; NS 1.68µm/min ±0.14, p Conclusions Peripheral neutrophils from symptomatic smokers share some migratory phenotypic features of patients with COPD, being as inaccurate though slower in their migratory pathways. This suggests that aspects of neutrophil dysfunction are an early marker of COPD susceptibility although further longitudinal studies are required.