Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review
Ruidi Tang, Jun-qing Yue, James D. Chalmers, Wei‐jie Guan
Abstract
Background and Objective: Bronchiectasis is a chronic respiratory disease characterized by predominantly neutrophilic inflammation, recurrent infection and pathological dilatation of the airways. Current therapeutic strategies primarily target infections and improving mucus clearance. However, no current treatment can directly ameliorate neutrophilic inflammation. Recently, dipeptidyl peptidase 1 (DPP-1) inhibitors effectively abrogated neutrophilic inflammation in bronchiectasis. This narrative review aimed to analyze the structural characteristics and functional effects of DPP-1, explore the mechanism of DPP-1 inhibitors in bronchiectasis, and highlight major clinical trial findings. Methods: We performed an online electronic search for relevant English literature on PubMed and Web of Science databases, with the keywords of "dipeptidyl peptidase 1", "cathepsin C", "cathepsin C structure", "cathepsin C maturation", "cathepsin C loss-of-function", "neutrophil serine proteases and bronchiectasis", "neutrophil serine proteases and cathepsin C", "neutrophil serine proteases and DPP-1", "DPP-1 inhibitors", "cathepsin C inhibitors", "DPP-1 inhibitors and bronchiectasis", "cathepsin C inhibitors and bronchiectasis". Two authors (R.D.T. and J.Q.Y.) independently searched and reviewed the articles. Key Content and Findings: trial. HSK31858 significantly decreased the exacerbation frequency and prolonged the time to the first exacerbation in the latest phase II trial among the Chinese population. Conclusions: DPP-1 inhibitors have exhibited promising effects in improving several major clinical outcomes in bronchiectasis via suppressing the activity of NSPs.