Introduction: Neutrophil dysfunction is a hallmark of bronchiectasis but the underlying mechanisms are unclear. Neutrophil metabolism is closely linked to function and is a potential therapeutic target in bronchiectasis.

Aim: To compare the metabolome of peripheral blood neutrophils from individuals with bronchiectasis compared to controls.

 Methods: Stable Bronchiectasis patients (n=80) and age-matched controls (n=62) were enrolled. Neutrophils were isolated from peripheral blood and metabolomics conducted by rapid HILIC-Z ion-mobility mass spectrometry (RHIMMS). Data was analysed using MetaboAnalyst.

Results: Untargeted analysis revealed distinct metabolomic profiles in bronchiectasis neutrophils compared to controls with differences in multiple metabolic pathways including metabolism of purine, nicotinate & nicotinamide, arginine biosynthesis, alanine, aspartate TCA cycle and glutamate. Figure 1 shows the 50 most differentially expressed metabolites. Hierarchical clustering comparing 3 bronchiectasis severity groups identified a cluster of metabolites including L-arginine, Inosine-5?-monophosphate, and delphinidin that were higher in moderate and severe disease. In response to in vitro stimulation with Resistin (a neutrophil granule protein increased in severe disease (1ug)) or LPS (5ug) neutrophils from controls showed metabolic changes, mainly driven by L-arginine and succinate.

 Conclusion: Peripheral blood neutrophils from patients with bronchiectasis have a distinct metabolomic profile, which alters with disease severity and may contribute to altered immune responses.