Abstract

Background: Patients with airway inflammation have increased levels of proteolytic enzymes in the sputum. While these molecules are important in regulating immune responses, excess proteolysis may contribute to tissue damage and disease progression. Extracellular matrix proteins (ECM), such as collagens and elastin are targets of proteolytic cleavage.

Objectives: The study aimed to quantify ECM fragments in the serum and sputum of patients with chronic airway inflammation and bronchiectasis (BE) as biomarkers for disease monitoring. We investigated the association of ECM breakdown products with different inflammatory profiles and protease expression in sputum.

Methods: 72 subjects with BE, COPD or primary immunodeficiency (PID), and healthy controls were sampled at the Royal Melbourne Hospital. ECM neo-epitopes produced by proteolytic cleavage of collagen and elastin, collagen formation and fibrinopeptides, as well as inflammatory markers were assessed in paired sputum and serum samples.

Results: MMP-degraded fragment of type I collagen (C1M) was significantly increased in the serum of all patient groups compared to healthy controls. C1M correlated positively with inflammatory markers, such as complement C9, IL6 and neutrophils in sputum. No increase of elastin cleavage products was observed in the circulation of BE patients, while they had elevated levels of inflammatory cytokines and neutrophilic inflammation in sputum, including neutrophil elastase.

Conclusion: ECM degradation products can be measured in the circulation of patients with airway inflammation and may be suited as disease-monitoring biomarkers. Further studies are required to ensure the accuracy of ECM quantification in sputum.