Integrating Brensocatib and CT Scans Into NCF Bronchiectasis Management: James Chalmers, MBChC, PhD

The use of CT scans is moving beyond a simple diagnostic tool for non–cystic fibrosis bronchiectasis to become a practical biomarker for assessing disease activity and monitoring treatment response, explained James D. Chalmers, MD, PhD, professor of respiratory medicine at the University of Dundee.

Imaging, specifically CT outcomes analysis, can help clinicians understand disease biology, risk-stratify patients, and evaluate the effectiveness of new therapies like the dipeptidyl peptidase 1 (DPP1) inhibitor brensocatib.

Chalmers presented the results of “Effect of Brensocatib on Computer Tomography Outcomes in Patients With Non–Cystic Fibrosis Bronchiectasis: An Analysis of the ASPEN Trial” during the CHEST 2025 Annual Meeting.

Transcript was lightly edited; captions were auto-generated.

Transcript

Do the findings from the CT outcomes analysis suggest that routine CT scans could become a more practical biomarker for monitoring disease activity and treatment response in patients with non–cystic fibrosis bronchiectasis vs just as a diagnostic tool?

CT is incredibly useful in the management of people with bronchiectasis. Obviously, it's how we make the diagnosis. You can't diagnose bronchiectasis reliably without a CT. I think what this data and what other emerging data suggests is that CT is also a useful biomarker of disease activity, by which I mean, how at risk is this patient? How badly are they going to do in the future? If you're looking at a CT scan with lots of mucus plugging, lots of bronchial wall thickening, lots of other changes that suggest inflammation, we now know inflammation equals risk of exacerbation, and so CT becomes one of the tools that we can use to endotype patients, meaning understanding their biology, and therefore risk stratify.

What's exciting about the CT data from Aspen is it suggests it can also be a biomarker of treatment response. So if you see an airway, a lung that's full of mucus, airways that are full of mucus, and we give a therapy, and at the end of a year, we see that that mucus is clearing, that's a sign that our patients are lower risk, and our treatments are working.

Given the heterogeneity of non–cystic fibrosis bronchiectasis, what characteristics best help clinicians identify the patients most likely to benefit from a DPP1 inhibitor like brensocatib?

You've asked me the question, are there biomarkers or patient characteristics that can predict who's going to respond to brensocatib? The answer is, I don't know. If you look at the ASPEN data—the ASPEN trial in over 1700 patients—the consistency of effect across all the subgroups was really remarkable. There was an overall 20% effect on exacerbations in both the 10-mg dose and the 25-mg dose across all of the prespecified subgroups, in terms of age, gender, lung function, infection status with pseudomonas, long-term macrolide, all of those other subgroups. The effect was remarkably consistent.

It's not that we can pick out one of those groups and say those patients are going to super respond to this therapy. The inflammation that brensocatib targets is a really universal trait across bronchiectasis, and it looks like, therefore, the effect is really very consistent, regardless of the patient characteristics. What I will say is, of course, the major effect of the treatment is to reduce exacerbations, so the more at risk a patient is of exacerbations, the more likely they are to benefit from the treatment.

Management of non–cystic fibrosis bronchiectasis often involves multiple therapies. How do you envision brensocatib being integrated into this existing treatment paradigm?

That's a really important question. Bensocatib is an important new tool for the treatment of bronchiectasis. It's not the only treatment that we have for management of bronchiectasis. It's not the only component of holistic management of bronchiectasis. I think brensocatib will be really important as a treatment to prevent exacerbations and slow down the progression of disease, alongside the other things that we can offer patients, which include airway clearance, which is the critical backbone of management.

Brensocatib is not going to change the fact that patients still need to do airway clearance alongside other therapies. Patients will still potentially experience exacerbations requiring antibiotic treatment. Patients may well still have chronic infections that require other prophylactic therapies that are recommended in our guidelines. I think it adds another very powerful tool on top of what we already have, but it certainly doesn't take away the need to use those backbone therapies.