Peptides for Bronchiectasis: Modulating Inflammation and Exacerbations

Written by Adam Maggio | Medically reviewed by Dr. Sarah Chen, PharmD, BCPS

Dipeptidyl peptidase-1 (DPP-1) inhibitors, particularly brensocatib, represent a significant advancement in peptide therapy for bronchiectasis. These agents effectively reduce exacerbation frequency and improve respiratory symptoms by modulating neutrophil serine protease activity, offering a targeted approach to managing this chronic lung condition.

Peptides: A New Era in Bronchiectasis Management

Bronchiectasis is a chronic lung condition characterized by permanent dilation of the airways, leading to recurrent respiratory infections, chronic cough, and excessive mucus production. The disease is often driven by a vicious cycle of inflammation and infection, making effective long-term management challenging. However, the advent of peptide-based therapies, particularly Dipeptidyl peptidase-1 (DPP-1) inhibitors, marks a significant step forward in addressing the underlying pathology of bronchiectasis.

DPP-1 Inhibitors: A Targeted Approach to Neutrophilic Inflammation

Dipeptidyl peptidase-1 (DPP-1), also known as cathepsin C, is a key enzyme involved in activating neutrophil serine proteases, which contribute significantly to the destructive inflammation seen in bronchiectasis. Inhibiting DPP-1 can therefore reduce the activity of these proteases, thereby dampening the inflammatory response. Brensocatib stands out as the first disease-specific therapy in this class to demonstrate efficacy in bronchiectasis. Clinical trials have shown that brensocatib can significantly reduce the annualized rate of pulmonary exacerbations and delay the time to the first exacerbation in patients with non-cystic fibrosis bronchiectasis (Chalmers et al., 2020; DocWireNews, 2025). The FDA approval of BRINSUPRI™ (brensocatib) in August 2025 underscores its breakthrough potential as the first and only treatment specifically for non-cystic fibrosis bronchiectasis.

Mechanism of Action: Beyond Symptomatic Relief

The primary mechanism of brensocatib involves reducing the activity of neutrophil serine proteases. These proteases, including neutrophil elastase, cathepsin G, and proteinase 3, are highly destructive enzymes released by neutrophils during inflammation. In bronchiectasis, their uncontrolled activity contributes to airway damage, mucus hypersecretion, and impaired host defense. By inhibiting DPP-1, brensocatib effectively limits the activation of these proteases, thereby mitigating lung tissue damage and chronic inflammation. This targeted approach offers a disease-modifying effect, moving beyond mere symptomatic relief to address the core pathological processes.

Other Peptide-Related Insights: Azurocidin-1

While DPP-1 inhibitors are at the forefront of peptide therapies for bronchiectasis, other peptide-related markers are also under investigation. Azurocidin-1 (AZU1) has been identified as a novel marker of disease severity in bronchiectasis, particularly associated with bacterial infection and exacerbation (Shoemark et al., 2025). Understanding such markers can help in better patient stratification and monitoring of disease progression, potentially guiding future peptide-based diagnostic or therapeutic strategies.

Peptide Therapies vs. Conventional Treatments

Conventional management of bronchiectasis typically involves antibiotics to control infections, mucolytics to clear mucus, and bronchodilators to improve airflow. While these treatments are essential for managing acute symptoms and preventing complications, they do not directly target the chronic neutrophilic inflammation that drives disease progression. DPP-1 inhibitors like brensocatib offer a distinct advantage by specifically modulating this inflammatory pathway. For instance, while antibiotics combat bacterial infections, brensocatib reduces the inflammatory damage caused by the host immune response itself. This contrasts with broad-spectrum anti-inflammatory drugs, which can have systemic side effects. Brensocatib's ability to reduce exacerbation frequency directly addresses a major clinical endpoint in bronchiectasis, offering a more proactive and disease-modifying strategy compared to the reactive nature of antibiotic use during exacerbations. This targeted immunomodulation represents a significant paradigm shift in treatment.

Clinical Takeaway

The emergence of peptide therapies, particularly DPP-1 inhibitors like brensocatib, marks a pivotal moment in the treatment of bronchiectasis. By specifically targeting the activation of destructive neutrophil serine proteases, these agents offer a novel and effective strategy to reduce chronic inflammation and prevent exacerbations. This targeted approach provides a significant advantage over conventional symptomatic treatments, promising improved lung function, reduced disease progression, and a better quality of life for patients with bronchiectasis. Continued research will further refine these peptide-based interventions and integrate them into comprehensive management protocols.