ASPEN Data Shed Light on Inflammation, DPP1 Class Cuts Exacerbations

On Monday, rapid-fire abstract sessions at CHEST 2026 drew so many attendees to a crowded corner off the exhibit floor that organizers ran out of headsets to drown out the din of activity. That didn’t stop listeners from leaning in to hear from the presenters at the session on CF and non-CF Management, who included the lead investigator from one of the field’s most consequential recent trials.

CHEST, the annual meeting of the American College of Chest Physicians, concludes Wednesday in Phoenix, Arizona.

How Green Is My Sputum: Color Tracks Neutrophil Inflammation, ASPEN Analysis Shows

How green a patient's sputum is may say a lot about inflammation in non–cystic fibrosis bronchiectasis, according to a post hoc analysis of the phase 3 ASPEN trial (NCT04594369) of brensocatib (Brinsupri; Insmed). James D. Chalmers, MBChB, PhD, of the University of Oxford, the investigator of ASPEN and senior author of the abstract, presented the results. Patrick A. Flume, MD, of the Medical University of South Carolina was first author.¹

Adult patients rated the color of their sputum every day using the Bronchiectasis Exacerbation and Symptom Tool (BEST). The ratings were grouped as mucoid, mucopurulent or purulent. Among the 326 patients with matching sputum biomarker data, darker sputum went with higher levels of neutrophil serine proteases (NSPs). Mean neutrophil elastase was 14.6 μg/mL in the mucoid group, 34.5 μg/mL in the mucopurulent group and 56.0 μg/mL in the purulent group. Patients with darker sputum also had worse disease overall: more Pseudomonas aeruginosa, more exacerbations, higher CT scores and lower lung function (FEV₁).

Brensocatib is an oral DPP1 inhibitor. Compared with placebo, it lowered NSP activity in all 3 sputum-color groups. It also reduced purulence scores during severe exacerbations. The authors noted that self-reported sputum color is subjective and that the subgroups were small. Even so, they said sputum purulence is still a useful, noninvasive way to monitor exacerbations. Insmed funded the study.

Meta-Analysis Finds DPP1 Inhibitors Cut Bronchiectasis Exacerbations by 25%

A meta-analysis led by Prasanna Sakthi Aravazhi, the first of 2 abstracts from this student at Madras Medical College, found that dipeptidyl peptidase-1 (DPP1) inhibitors cut exacerbations in adults with non–cystic fibrosis bronchiectasis without adding safety problems.² The analysis pooled 3 randomized, placebo-controlled trials: WILLOW, ASPEN and SAVE-BE. Together they enrolled 2913 patients, with 1485 receiving a DPP1 inhibitor and 1428 receiving placebo.

Compared with placebo, DPP1 inhibition lowered the exacerbation rate by 25% (RR, 0.75; 95% CI, 0.68-0.82; P < .001). It also delayed the first exacerbation (HR, 0.78) and reduced the share of patients who had any exacerbation (RR, 0.82). The benefit was greater with the higher dose of HSK31858 and similar across brensocatib doses. Lung function barely changed, and respiratory quality-of-life scores improved modestly. Rates of adverse events, serious adverse events and discontinuations were similar to placebo.

Machine Learning Model Finds Biology, Not Demographics, Drives Bronchiectasis Exacerbation Risk

In a second study, Aravazhi and colleagues built a machine learning model that predicts which adults with bronchiectasis will have frequent exacerbations. It was designed to be explainable, meaning clinicians can see which factors drive each prediction. The analysis included 7400 patients with mean age 66.8 years, and 62% were women. Within 12 months, 17.3% had 2 or more exacerbations.³

The gradient boosting model discriminated moderately well (AUROC, 0.74) and had 83.2% overall accuracy. Specificity was 98.2%, but sensitivity was only 11.7%, so the model missed most high-risk patients at its default setting. The strongest predictors were prior exacerbations, chronic Pseudomonas colonization, lower FEV₁, elevated C-reactive protein and more lobes involved. Age, sex and smoking history mattered far less. The authors said this kind of tool could help clinicians target treatment before exacerbations happen.

Sjögren’s-Associated Bronchiectasis Carries a Heavy Burden, Registry Data Show

Bronchiectasis affects an estimated 23% to 54% of patients with Sjögren’s syndrome, but the disease in this group has not been well described. The final presenter, Adrienne Strait, MD, a current fellow at UCSF, said she and colleagues used the US Bronchiectasis and NTM Research Registry (nontuberculous mycobacteria), to compare 71 patients with Sjögren’s-associated bronchiectasis with 190 patients whose bronchiectasis was linked to rheumatoid arthritis and 604 with idiopathic disease.⁴

Patients with Sjögren’s were mostly women (94.3%), with a median age of 69 years. More than half (57.7%) had gastroesophageal reflux disease, and CT scans showed a median of 4 affected lobes. In the 2 years before enrollment, 53.6% had at least 1 exacerbation and 21.1% were hospitalized for a lung-related problem. More than half (54.9%) had at least 1 positive culture for nontuberculous mycobacteria, 22.5% for Staphylococcus aureus and 14.1% for Pseudomonas aeruginosa.

Overall, the Sjögren’s group looked similar to the other 2 groups clinically and microbiologically. The study was underpowered, but the authors said it hinted at more exacerbations and S aureus infection than in idiopathic disease. They said these patients merit dedicated bronchiectasis care and possibly routine respiratory cultures.

References

1. Flume PA, Aliberti S, Goeminne P, et al. Patient-reported sputum color and its association with neutrophil serine proteases and exacerbations in patients with bronchiectasis: a post hoc analysis of the ASPEN trial. Chest. 2026;170(suppl 4):abstr 7.715. doi:10.1016/j.chest.2026.07.715.
2. Aravazhi PS, Gunasekaran P. Dipeptidyl peptidase-1 inhibitors’ safety and effectiveness in noncystic fibrosis bronchiectasis: a systematic review and meta-analysis of randomized trials. Chest. 2026;170(suppl 4):abstr 7.181. doi:10.1016/j.chest.2026.07.181
3. Aravazhi PS, Harshawardhan RK, Ramteke D, et al. Externally validated explainable machine learning model for predicting 12-month exacerbation risk in bronchiecstatis. Chest. 2026;170(suppl 4):abstr 7.179. doi:10.1016/j.chest.2026. 07.179.
4. Strait A, Brunton A, Aksamit TR, et al. Bronchiectastis in Sjogren’s syndrome: data from the US Bronchiectasis and NTM Research Registry. Chest. 2026;170(suppl 4):abstr 7.182. doi:10.1016/j.chest.2026. 07.182.