Neutrophil extracellular traps, disease severity and airway infection in bronchiectasis: preliminary results from the BRILLIANT study

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Rationale: Bronchiectasis is a heterogenous disease. This study employed comprehensive sampling and clinical analyses to characterise inflammation and links with clinical and pathophysiological features of bronchiectasis. Methods: Ongoing prospective observational study recruiting stable participants with CT-confirmed bronchiectasis and controls. Analyses included chest CT, PFTs, blood neutrophil isolation, bronchoscopy with bronchial biopsy and bronchoalveolar lavage (BAL), plus airway microbiome, BAL proteome, immune cell, and mucociliary analyses. Results: 47 people with bronchiectasis (55% female; age 65±12; 44.6/46.8/8.5% mild/moderate/severe BSI) and 20 controls were included. People with bronchiectasis had higher levels of spontaneous BAL cell ex vivo NETs (median[IQR]: 30740[12489-57033] vs. 7852[5284-12166]A.U., p<0.00001) and BALF DNA-NE complexes (4.4[0.3-73.7] vs. 0.1[0.0-0.1]A.U., p<0.0001) vs. controls. Ex vivo BAL cell NETs negatively correlated with FEV1 (r=-0.41, p=0.17). Although blood neutrophil phagocytosis of P. aeruginosa and ex vivo blood neutrophil NETs were not different between groups, they were significantly negatively correlated in bronchiectasis (r=-0.42, p<0.01). Airway levels of the neutrophil granule protein azurocidin-1 were higher in patients positive for bacteria or viruses in BAL via Biofire PCR panel (67.4[9.3-208.4] vs. 5.4[1.8-68.1] µg/ml, p=0.019) and negatively correlated with microbiota diversity (Shannon: r=-0.69, Simpson: r=-0.66, p<0.001). Conclusion: Confirming and extending previous studies using sputum, we show that airway NETs are associated with disease severity and microbial infection in bronchiectasis.

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