ASPEN: Sputum Color Associated With Bronchiectasis Disease Activity

Greater patient-reported sputum purulence was associated with higher neutrophil serine protease (NSP) activity and greater disease activity in patients with bronchiectasis, according to a post hoc analysis of the phase 3 ASPEN trial presented at the American College of Chest Physicians (CHEST) 2026 Annual Meeting, held October 18 to 21 in Phoenix, Arizona.^1,2

Brensocatib (Brinsupri), an oral dipeptidyl peptidase 1 inhibitor, reduces NSP activation and is approved in the US for non-cystic fibrosis bronchiectasis in patients aged 12 years and older.¹ In ASPEN, both brensocatib doses reduced the annualized rate of pulmonary exacerbations vs placebo.³ The current analysis evaluated whether daily patient-reported sputum color reflects underlying NSP activity and how brensocatib affects these measures.¹

"Sputum is a noninvasive marker of airway inflammation, with purulence reflecting the presence and activity of neutrophils in the airways," said James Chalmers, MBChB, PhD, professor and Asthma and Lung UK Chair of Respiratory Research, University of Dundee. "It's a valuable tool for monitoring bronchiectasis exacerbations."²

Sputum purulence and neutrophil elastase activity in ASPEN

ASPEN (NCT04594369) randomized adults with at least 2 pulmonary exacerbations in the prior 12 months 1:1:1 to once-daily brensocatib 10 mg, brensocatib 25 mg, or placebo for 52 weeks.¹ Patients rated sputum purulence daily on a 6-point color scale within the Bronchiectasis Exacerbation and Symptom Tool (BEST) diary, and investigators aligned responses post hoc to Murray chart categories of mucoid, mucopurulent, and purulent.¹ Sputum neutrophil elastase (NE), cathepsin G (CatG), and proteinase 3 (PR3) were measured in a subset of patients through week 56.¹

Among 326 patients with corresponding sputum NSP data, 36.2% (118/326) reported mucoid, 43.9% (143/326) mucopurulent, and 19.9% (65/326) purulent sputum at baseline.¹ Baseline geometric mean NE activity rose with purulence, from 14.6 μg/mL in the mucoid group to 34.5 μg/mL in the mucopurulent group and 56.0 μg/mL in the purulent group.¹ The association persisted across the treatment period, with similar trends for CatG and PR3.¹

Greater baseline purulence was also associated with higher sputum neutrophil counts, Pseudomonas aeruginosa positivity, exacerbation rates, and Bronchiectasis-Computed Tomography scores, as well as lower postbronchodilator percent predicted forced expiratory volume in 1 second (FEV1).¹

Brensocatib effect on NE activity by baseline sputum color

Brensocatib was associated with greater reductions in NE activity than placebo across all purulence categories.¹ Median percent reductions from baseline in the mucoid group were 0.0% with placebo, 12.0% with brensocatib 10 mg, and 42.8% with brensocatib 25 mg.¹

In the mucopurulent group, median reductions were 20.4%, 26.8%, and 32.7%, respectively, and in the purulent group, 13.6%, 58.8%, and 45.6%.¹ Similar trends were observed for CatG and PR3.¹ The abstract did not report P values or measures of dispersion for these comparisons.

Sputum purulence increased in all treatment arms during pulmonary exacerbations regardless of severity.¹ During severe exacerbations, defined as those requiring intravenous antibiotics and/or hospitalization, both brensocatib doses reduced sputum purulence scores vs placebo.¹ Numerical results for this comparison were not included in the abstract.

"With the recent FDA approval of brensocatib for the treatment of bronchiectasis in adults and adolescents, we wanted to evaluate its impact on sputum color," Chalmers said.²

The analysis was post hoc, the purulence categories were derived retrospectively, and NSP data were available only for a subset of the ASPEN population.¹

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 from the ASPEN trial. CHEST. 2026;170(4S). doi:10.1016/j.chest.2026.07.175

2. American College of Chest Physicians. Patient-reported sputum color reflects airway inflammation and exacerbations in bronchiectasis. News release. October 12, 2026. Accessed October 18, 2026.

3. Chalmers JD, Burgel PR, Daley CL, et al. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N Engl J Med. 2025;392(16):1569-1581. doi:10.1056/NEJMoa2411664