Sputum Color Flags Severity in Bronchiectasis: James Chalmers, MBChB, PhD

Patient-reported sputum color reflected neutrophil serine protease (NSP) activity and overall disease activity in bronchiectasis, and brensocatib (Brinsupri) reduced neutrophil elastase (NE) activity across all sputum color categories in a post hoc analysis of the phase 3 ASPEN trial.¹ James Chalmers, MBChB, PhD, Rhodes Professor of Experimental Therapeutics and Clinical Pharmacology at the University of Oxford, discussed the findings with HCPLive.

Chalmers presented the analysis at the CHEST 2026 Annual Meeting, held October 18-21, 2026, in Phoenix, Arizona, building on initial results reported during the meeting. ASPEN (NCT04594369) randomized adults with at least 2 pulmonary exacerbations in the prior 12 months to once-daily brensocatib 10 mg, 25 mg, or placebo for 52 weeks, with patients rating sputum color daily on the Bronchiectasis Exacerbation and Symptom Tool (BEST) diary.^1,2 Of 326 patients with sputum NSP data, 36.2% reported mucoid, 43.9% mucopurulent, and 19.9% purulent sputum at baseline.

"Although sputum color is simple, and so you think, well, it cannot be that good at telling us these things, it was remarkably good at identifying patients who had frequent exacerbations, who had a higher burden of symptoms, overall a more severe clinical course, and a higher disease severity," Chalmers said.

Baseline geometric mean NE activity rose from 14.6 µg/mL with mucoid sputum to 34.5 µg/mL with mucopurulent and 56.0 µg/mL with purulent sputum, with similar trends for cathepsin G and proteinase 3.¹ Greater purulence was also associated with higher sputum neutrophil counts, Pseudomonas aeruginosa positivity, exacerbation rates, and Bronchiectasis-Computed Tomography scores, and with lower postbronchodilator FEV1 % predicted. Chalmers said neutrophil-derived myeloperoxidase drives green sputum color, making purulence a bedside proxy for neutrophilic inflammation.

Brensocatib was associated with greater NE reductions than placebo in every purulence category, including median reductions of 42.8% with 25 mg versus 0.0% with placebo in mucoid sputum and 58.8% with 10 mg versus 13.6% with placebo in purulent sputum.¹ Chalmers said patients with mucoid sputum can still be inflamed and benefit, a point relevant to growing interest in treating earlier disease.

Sputum purulence rose during exacerbations in all arms, but both brensocatib doses lowered purulence scores versus placebo during severe exacerbations.¹ Chalmers said this suggests brensocatib may change the course of exacerbations, though the analysis was not powered for the question. These post hoc data have not been published in full.

Disclosures include Insmed.

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. doi:10.1016/j.chest.2026.07.175

2. 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.