Sputum Color Tracks Inflammation, Brensocatib Effect in Bronchiectasis

Sputum is considered a noninvasive marker of airway inflammation, and its color is an indicator of bronchiectasis disease activity, severity, and inflammation.¹

A post hoc analysis of the phase 3, double-blind ASPEN trial (NCT04594369)—which assessed the annualized rate of adjudicated pulmonary exacerbations—found that patient-reported sputum color tracked with neutrophil serine protease (NSP) activity and disease activity and that brensocatib (Brinsupri; Insmed) was associated with reduced NSP activity across all sputum color categories and reduced sputum purulence scores during severe exacerbations compared with placebo.¹ The post hoc analysis assessed patient-reported sputum color to further support evidence of its usefulness as an inflammatory biomarker that can help clinicians assess bronchiectasis in clinical practice. The analysis was presented at the CHEST 2026 Annual Meeting, held October 18-21, 2026, in Phoenix, Arizona.

“It’s a valuable tool for monitoring bronchiectasis exacerbations,” James Chalmers, MBChB, PhD, from the University of Oxford, an ASPEN investigator and CHEST 2026 presenting author, said in a written statement. “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.”²

Brensocatib was approved in August 2025, becoming the first therapy approved to treat noncystic fibrosis bronchiectasis and the first dipeptidyl peptidase 1 (DPP1) inhibitor approved to treat a neutrophil-mediated disease.³ It is now approved in the US, the European Union, and the United Kingdom to treat noncystic fibrosis bronchiectasis in patients 12 years and older. In the EU and UK, approval is limited to patients with at least 2 pulmonary exacerbations in the prior 12 months.¹

How Sputum Color Tracked With Neutrophil Serine Protease Activity

The post hoc analysis pooled data from 326 patients across treatment arms who had corresponding sputum NSP data. Sputum purulence was assessed using patient-reported responses to the Bronchiectasis Exacerbation and Symptom Tool (BEST), and sputum samples were analyzed for NSP activity, including neutrophil elastase (NE), cathepsin G (CatG), and proteinase 3 (PR3).¹

In the ASPEN trial, patients were randomized 1:1:1 to receive once daily brensocatib 10 mg or 25 mg or placebo for 52 weeks. The BEST diary, completed daily, evaluated breathlessness, cough, cold and flu symptoms, sputum volume, sputum purulence, and fatigue. Sputum purulence was rated on a 6-point color scale and grouped as mucoid (clear and white), mucopurulent (yellow), or purulent (green, dark green, or blood).¹

Of the 326 patients included in the pooled analysis, 118 (36.2%) reported mucoid, 143 (43.9%) reported mucopurulent, and 65 (19.9%) reported purulent sputum at baseline. Greater sputum purulence was associated with higher sputum NE activity at baseline (geometric mean, 14.6 µg/mL, 34.5 µg/mL, and 56.0 µg/mL for mucoid, mucopurulent, and purulent sputum, respectively) and across the entire treatment period, with similar trends for CatG and PR3. At baseline, greater purulence was also associated with greater disease activity, including higher sputum neutrophil counts, Pseudomonas aeruginosa positivity, exacerbation rates, and bronchiectasis-computed tomography scores, as well as lower postbronchodilator FEV1 (% predicted).¹

Brensocatib Lowered Neutrophil Elastase Across Sputum Color Categories

Brensocatib was associated with greater reductions in NE when compared with placebo across all 3 sputum purulence categories. The median percent reductions from baseline were as follows: mucoid, 0.0%, 12.0%, and 42.8%; mucopurulent, 20.4%, 26.8%, and 32.7%; and purulent, 13.6%, 58.8%, and 45.6% for placebo, brensocatib 10 mg, and brensocatib 25 mg, respectively. Similar trends were observed for CatG and PR3.¹

Sputum purulence increased across all treatment arms during pulmonary exacerbations, regardless of severity. However, both brensocatib doses reduced sputum purulence scores vs placebo during severe exacerbations, defined as those requiring intravenous antibiotics and/or hospitalization.¹

“This FDA approval represents a potential paradigm shift in how we approach noncystic fibrosis bronchiectasis,” Doreen Addrizzo-Harris, MD, FCCP, the Fiona and Stanley Druckenmiller Professor of Pulmonary, Critical Care, and Sleep Medicine at NYU Grossman School of Medicine, director of the NYU Langone Health Bronchiectasis and NTM Program, and an ASPEN investigator, said in a statement when brensocatib was first approved. “For the first time, we have a treatment that directly targets neutrophilic inflammation and addresses a root cause of bronchiectasis exacerbations. Based on the strength of the data and the impact we’ve seen in patients, I believe this could become the new standard in noncystic fibrosis bronchiectasis care.”³

The sputum color analysis was one of several bronchiectasis abstracts presented at CHEST 2026, alongside a meta-analysis of DPP1 inhibitor trials, a machine learning model to predict exacerbation risk, and a registry study of Sjögren’s-associated bronchiectasis.⁴

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. Presented at: CHEST 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ. doi:10.1016/j.chest.2026.07.175

2. Patient-reported sputum color reflects airway inflammation and exacerbations in bronchiectasis. News release. CHEST. October 12, 2026. Accessed October 28, 2026. https://www.chestnet.org/-/media/documents/news/04-patient-reported-sputum-color-reflects-airway-inflammation-and-exacerbations-in-bronchiectasis-jc-ld_bd.ashx?_gl=1*16m9iyt*_up*MQ..*_ga*MTkwNTg1OTgwNC4xNzkzMTkxODU3*_ga_3W3R3BBY66*czE3OTMxOTE4NTckbzEkZzAkdDE3OTMxOTE4NTckajYwJGwwJGgw

3. McCormick B. Brensocatib becomes first FDA-approved therapy for bronchiectasis. AJMC. August 12, 2025. Accessed October 28, 2026. https://www.ajmc.com/view/brensocatib-becomes-first-fda-approved-therapy-for-bronchiectasis

4. Caffrey M. ASPEN data shed light on inflammation, DPP1 class cuts exacerbations. AJMC. October 20, 2026. Accessed October 28, 2026. https://www.ajmc.com/view/aspen-data-shed-light-on-inflammation-dpp1-class-cuts-exacerbations