Sputum cathepsin G activity predicts exacerbations and hospitalisations in bronchiectasis

Bronchiectasis is a neutrophil-driven inflammatory chronic respiratory disease. While neutrophil elastase has been deeply investigated, other neutrophil serine proteases are less studied. The association between airway cathepsin G and clinical outcomes in bronchiectasis has not been described. Is cathepsin G sputum activity associated with clinical outcomes in bronchiectasis?

This international, multicentre, prospective cohort study enrolled bronchiectasis patients from three bronchiectasis programmes in Milan (Italy), Dundee (UK) and Barcelona (Spain). Participants were stratified into three groups based on sputum cathepsin G activity measured using immunoassays. Data on clinical features, sputum characteristics, exacerbations, hospitalisations and mortality were collected over a 3-year follow-up period.

The median (interquartile range) activity of cathepsin G in sputum was 45.1 ng·mL^-1 (1.3-128.8 ng·mL^-1). Patients with higher sputum cathepsin G activity demonstrated significantly worse clinical outcomes in terms of disease severity (measured by the Bronchiectasis Severity Index, E-FACED, the modified Reiff score, % predicted forced expiratory volume in 1 s and the prevalence of chronic bacterial infections, particularly Pseudomonas aeruginosa) and disease activity (daily produced sputum volume and quality of life scores). Additionally, high cathepsin G activity was linked to more frequent exacerbations during the 3-year follow-up (incidence rate ratio 1.62, 95% CI 1.29-2.07) and a greater risk of hospitalisation due to severe exacerbations (incidence rate ratio 2.32, 95% CI 1.03-5.21). A strong correlation was found between sputum cathepsin G and neutrophil elastase activities.

Sputum cathepsin G activity relates to disease severity, disease activity and prognosis in bronchiectasis. High cathepsin G levels are associated with more severe clinical outcomes and could serve as a target for future therapeutic interventions, including dipeptidyl peptidase 1 inhibitors.