Pharmacotherapy options and drug development in bronchiectasis: spotlight on dipeptidyl-peptidase inhibitors

Introduction: In recent years, the central role of inflammation in the development and persistence of the vicious vortex of bronchiectasis has become increasingly evident, gradually reshaping the therapeutic landscape. Historically, treatment strategies have focused mainly on controlling infection, alleviating symptoms, and enhancing mucociliary clearance. However, accumulating evidence indicates that targeting the inflammatory component represents an important complementary strategy in bronchiectasis management. Areas covered: Within this evolving framework, novel anti-inflammatory approaches are emerging, including the inhibition of dipeptidyl peptidase-1 (DPP-1) which can reduce neutrophil-driven airway inflammation and, consequently, exacerbations. The recent regulatory approval of brensocatib, a DPP-1 inhibitor, represents a milestone in the development of targeted therapies for bronchiectasis. This review provides a narrative overview of available treatments for bronchiectasis, with a particular focus on DPP-1 inhibitors, and discusses their potential role and integration into clinical practice. Expert opinion: The emergence of DPP-1 inhibitors reflects a paradigm shift in bronchiectasis care. While promising, their role remains to be fully defined due to a lack of long-term real-world evidence and comparative studies against established strategies. A major challenge will be identifying the patients most likely to benefit. Despite uncertainties, these agents have the potential to redefine treatment for this complex disease.