Introduction: Proteinase-3 (PR3) is a neutrophil serine protease similar in structure and function to neutrophil elastase (NE), a marker of disease severity and exacerbation risk in Bronchiectasis. PR3 is a target of the recently developed DPP1 inhibitors in clinical trials for bronchiectasis. We investigated whether sputum PR3 activity relates to disease severity in patients with adult bronchiectasis.

Methods: PR3 activity was measured using ProAxis Protease Tag immunoassay in sputum supernatant from clinically stable patients enrolled in a pan-European multicentre observational study (EMBARC-BRIDGE study). Clinical severity markers included lung function, exacerbations, microbial infection, BSI score and radiological parameters.

Results: 181 patients were included for analysis. Mean age was 65 (± 16) and 49.1% were female. Median sputum PR3 concentration was 373 ng/ml (IQR 139-1433). Median PR3 concentration was significantly higher patients with chronic P.aeruginosa infection at 1253 (IQR 638-7275) versus 227 (IQR 117-1069) (p=0.002). Sputum purulence (p=0.002), presence of mucus plugging (p=0.006) and consolidation (p=0.033) on chest CT, previous hospitalisation for bronchiectasis (p=0.014) and FEV1 <80% predicted (p=0.02) were also associated with increased PR3. BSI score, MRC dyspnoea score and number of exacerbations in the previous year had no significant relationship with PR3. Sputum PR3 correlated with sputum NE (r 0.556, p<0.001), and IL-8 (r 0.743, P<0.001).

Conclusion: Sputum PR3 is raised in association with clinical and radiological markers of active lung inflammation and infection. Activity and effects of PR3 in bronchiectasis warrants further investigation.