Characterisation of blood and airway neutrophils in bronchiectasis

Bronchiectasis is a chronic progressive respiratory disease with wide-ranging aetiology. In bronchiectasis, interplay of a ‘vicious vortex’ of lung structural remodeling, inflammation, impaired mucociliary clearance, and infection exacerbates each other. Inflammation in bronchiectasis is primarily neutrophilic. Research into the action of neutrophils taken from the lung at the site of bronchiectasis is lacking and their functional capabilities are largely unknown with only some small studies measuring lung neutrophil functions. Here we describe an uncertain role of platelets in bronchiectasis, demonstrating activation of neutrophils by platelets and the formation of neutrophil-platelet aggregates but also a potentially protective association of neutrophil-platelet aggregates on lung function in bronchiectasis and no change in neutrophil function between those with higher and lower neutrophil-platelet aggregate formation. We show that the lung in bronchiectasis is highly neutrophilic compared to healthy controls but that the total number of leukocytes within the BAL fluid was not increased in bronchiectasis possibly due to an increase in the lymphocytes and macrophages in controls. Data presented here demonstrates that NETosis is greatly increased in bronchiectasis patient lung neutrophils and corresponds with increased soluble NET complexes measured in BAL fluid. Both measures are shown to be associated with bronchiectasis disease severity and lung function. Blood and BAL-derived neutrophil functions of apoptosis, NETosis, migration, bacterial killing and phagocytosis and their associations with clinical parameters is characterised in bronchiectasis patients compared to a control population. A difference in neutrophil phagocytosis and apoptosis that has been previously described was not identified in these patients. The robust association between lung NETs and increased bronchiectasis disease severity necessitates further exploration of NETosis inhibition as a therapeutic strategy for the treatment of bronchiectasis.