Navigating Access to Bronchiectasis's First DPP1 Inhibitor

"Navigating Access to Bronchiectasis's First DPP1 Inhibitor" looks at how brensocatib has changed Dr. Sala's treatment options, and the questions it still leaves unanswered.

Dr. Sala describes brensocatib, approved in August 2025, as the first bronchiectasis-specific therapy targeting neutrophil elastase, giving clinicians a genuinely new tool for addressing airway inflammation. Before its approval, he explains, management relied almost entirely on treating chronic infections and using off-label anti-inflammatory strategies like thrice-weekly azithromycin, alongside airway clearance. Brensocatib now offers patients with frequent, debilitating exacerbation seasons another option grounded in a specific underlying biological mechanism rather than broad-spectrum anti-inflammatory effect. Approved for ages 12 and up, Dr. Sala calls it an important proof of concept and hopes it is the first of several therapies targeting this pathway, though he stresses it currently treats bronchiectasis after diagnosis rather than preventing it from developing in the first place for at-risk individuals.

Looking ahead, Dr. Sala identifies the field's true "holy grail" as identifying at-risk individuals and intervening before bronchiectasis ever develops, a goal he considers years away. More immediately, he raises an unresolved question: DPP1 inhibitor trials generally excluded immunocompromised and immunosuppressed patients, yet many of his own patients have autoimmune disease or impaired immunity that directly drives their infections and exacerbations. Whether these therapies are safe and effective in that population remains unknown, he says, and if they aren't appropriate, clinicians still need alternative strategies for them. Dr. Sala describes patients at the intersection of structural lung disease and impaired host immunity as among the hardest to manage, since no amount of airway clearance or immunomodulation fully compensates when the immune system itself cannot clear infection effectively on its own.

Our next episode, "Combining DPP1 Inhibition With Existing Bronchiectasis Therapies," examines how Dr. Sala actually sequences brensocatib alongside the therapies patients may already be taking.