Proteinase-3 as a biomarker of exacerbations in bronchiectasis

Introduction: Proteinase 3 (PR3) is a serine protease stored in the primary granules of neutrophils and similar in structure to neutrophil elastase (NE). We sought to investigate the role of PR3 in exacerbations of bronchiectasis. Methods: PR3 activity in sputum supernatant was measured using a proteaseTag immunoassay in 86 individuals in stable state and during an exacerbation. Severity of disease was evaluated using the bronchiectasis severity index (BSI) and FACED, forced expiratory volume in 1 second (FEV1) and correlated with established biomarkers of bronchiectasis severity including NE and Heparin binding protein (HBP). Results: Median PR-3 concentration during stable state was 2.81µg/ml (IQR3.35-2.17) and 3.07 µg/ml (IQR3.47-2.53). during exacerbation. Mean age of patients enrolled was 65 and 55% were female. Mean BSI score was 8.2 (SD4.1) and mean FEV1 was 73.3% predicted (SD22.56). PR3 concentration was raised by mean of 43% during exacerbations (p=0.047) PR-3 concentrations showed a weak positive correlation to other neutrophilic markers in sputum such as NE (r=0.29, p=0.007) and HBP (r= 0.44, p<0.0001. NE (p=0.01) was also clearly increased at exacerbation. PR3 measured at stable state did not demonstrate a correlation with severity (BSI or FACED) or radiological scores. It also failed to correlate to FEV1 at baseline or MRC dyspnoea scores. This was in contrast to NE and HBP which were significantly correlated with severity, Pseudomonas aeruginosa infection, FEV1 and other markers of severity. Conclusions: PR-3 measured in sputum is raised during exacerbations of bronchiectasis and further studies should establish its therapeutic implications and to determine its role in the pathogenesis of bronchiectasis.