Proteinase 3 activity is present in sputum from subjects with alpha-1-antitrypsin deficiency (AATD) and COPD

Introduction In COPD an imbalance is thought to exist between the activity of proteinases & their inhibitors. Neutrophil elastase (NE) has been studied in detail but proteinase 3 (PR3) has not. PR3 causes features of emphysema in animals & is more abundant in neutrophils than NE suggesting it may also play a role. Aims To investigate the importance of PR3 in AATD & COPD. Methods Spontaneous sputum was collected from 28 AATD & 24 usual COPD patients who were clinically stable, and from 15 of the COPD patients during an exacerbation. Patients had demographic data collected, lung function tests & quality of life scores. The sol-phase of sputum was analysed for NE & PR3 activities using specific substrates. The concentration of these proteinases was also measured by ELISA together with airway inhibitors & markers of neutrophilic inflammation. Results Most sputum samples had no detectable NE activity, but PR3 activity was present & higher than NE activity (AATD p=0.0043, COPD p=0.0052). PR3 activity was higher in AATD patients compared to COPD patients (p=0.0023) & was higher during exacerbations than in stable state in COPD patients (p=0.037). PR3 activity showed positive correlations with markers of neutrophilic inflammation & quality of life score. No correlations were found with lung function. The main airway inhibitor of NE is secretory leukoproteinase inhibitor which does not inhibit PR3. The data suggests that concentrations of PR3 exceed the inhibitory capacity especially in AATD, but NE does not. Conclusion Active PR3 is present in sputum from stable patients with AATD & COPD and is greater than active NE indicating it may play a role in the pathophysiology of airways disease.