S86 Role of oxidative stress in severe asthma

Abstract

Introduction Asthma affects 300 million people world-wide and is severe in 10% of sufferers. Existing literature suggests that oxidative stress is implicated in asthma pathogenesis, however, there is limited data characterising its role in severe asthma. It’s not fully established whether higher levels of oxidative stress are associated with specific aetiological factors, such as bacterial infection and airway inflammation. Aims I sought to quantify sputum differential cell counts, bacterial load and oxidative stress levels in severe asthmatics, assess relationships between these parameters and ascertain whether they impact on asthma control, and risk of exacerbations. Methods An 8-oxodG ELISA quantifying oxidative stress and quantitative PCR measuring total bacterial load were performed on sputum supernatant of 128 subjects, attending a tertiary referral severe asthma centre. Sputum differential cell counts were measured and subjects were stratified according to severity of oxidative stress (high >2 ng/ml 8-oxodG) and bacterial load (high >107 copies/ml total 16S). Longitudinal asthma control (ACQ6) and exacerbations were recorded. Results Higher sputum neutrophils were observed in oxidative stressHIGH subjects versus oxidative stressLOW (Mann-Whitney median (IQR) 81.5 (59.25–95) vs 64.6 (38.9–85.31), p=0.020). Sputum neutrophil percentage and bacterial load showed positive correlation (r=0.29, p=0.0009) however, eosinophils were negatively correlated with total 16S levels (r=−0.23, p=0.0086). 4 groups formulated upon bacterial load and oxidative stress levels, showed a significant difference in neutrophil count (Kruskal-Wallis p=0.045); oxidative stressHIGH/bacterial loadHIGH subjects had the highest neutrophil count versus subjects that were oxidative stressLOW/bacterial loadLOW (Mann-Whitney median (IQR) 81.66 (72.5–95) vs 64.6 (38.9–85.94), p=0.0074). There was no difference in baseline nor change in ACQ between these groups existed, but those that were oxidative stressLOW/bacterial loadLOW had a lower exacerbation frequency (Kruskal-Wallis p=0.027) (table 1). Discussion Oxidative stress together with bacterial load are associated with neutrophilic inflammation. Future exacerbation risk was lowest in asthmatics with a low bacterial load burden and oxidative stress. Whether oxidative stress is a consequence or cause of bacterial load and neutrophilic inflammation remains unknown, but my findings suggest that studying treatments targeting oxidative stress in asthma and the consequent effects upon neutrophilic inflammation, bacterial load and clinical outcomes is warranted.