Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast

Bronchiectasis is a chronic and progressive inflammatory lung disease characterized by dilated airways, impaired mucociliary clearance, recurrent infections, and inflammation. In this podcast, we discuss the heterogeneous causes and complex pathophysiology of bronchiectasis, reviewing the therapeutic tools we currently have available to target aspects of the vicious vortex that drives disease progression. Patient evaluation involves identifying underlying causes such as autoimmune diseases or immune deficiencies, conducting sputum cultures for bacteria, fungi, and mycobacteria, and performing pulmonary function tests. The primary objectives of treatment are to alleviate symptoms, reduce burdensome exacerbations, enhance quality of life, and slow disease progression, requiring shared decision-making to align clinical and patient priorities. Effective management necessitates a multimodal approach to address all aspects of pathophysiology including airway obstruction, infection, and inflammation. An unmet need remains to fully address the inflammation, which is predominantly neutrophilic, driving bronchiectasis. Emerging therapies that directly target dysregulated neutrophilic inflammation via inhibition of the enzyme dipeptidyl peptidase 1 (DPP1) reduce neutrophil serine protease (NSP) activity. Brensocatib, an oral, once-daily DPP1 inhibitor, was recently approved by the FDA and is indicated in the USA for the treatment of noncystic fibrosis bronchiectasis in adult and pediatric patients 12 years of age and older. In the phase 3, 52-week ASPEN trial, brensocatib significantly reduced exacerbation burden, and the 25-mg dose reduced lung function decline and nominally significantly improved patient-reported symptoms compared with placebo. Additional therapies in development include other DPP1 inhibitors (verducatib and HSK31858) and drugs targeting phosphodiesterase 3/4 inhibition (ensifentrine) and anti-interleukin-33 (itepekimab). Overall, the future is promising for patients with the historically neglected and underdiagnosed disease bronchiectasis, with growing awareness and new therapeutic tools becoming available. Podcast (MP4 81554 KB).