The dipeptidyl peptidase (DPP) family comprises enzymes with important metabolic and immunomodulatory properties. This narrative review summarizes recent clinical and experimental evidence on the role of DPP-1, DPP-4, DPP-9, and DPP-10 in pulmonary diseases. The strongest translational evidence currently supports DPP-1 inhibition in non-cystic fibrosis bronchiectasis, where brensocatib reduces exacerbations and prolongs time to first exacerbation, with additional DPP-1 inhibitors in development. By contrast, the roles of DPP-4, DPP-9, and DPP-10 are supported mainly by preclinical studies in pulmonary hypertension, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), pulmonary fibrosis, asthma, non-small cell lung cancer (NSCLC), and nonsteroidal anti-inflammatory drugs (NSAIDs)/aspirin-exacerbated respiratory disease. Across these models, DPP inhibition modulates inflammation, protease activation, epithelial or endothelial mesenchymal transition, extracellular matrix (ECM) remodeling, and related signaling pathways. Overall, DPP-targeted interventions are promising in pulmonary medicine, but broader clinical translation will require well-designed prospective trials.
Panou et al. (Tue,) studied this question.