Eosinophils, CC16, and the Role of COPD Biomarkers, with Francesca Polverino, MD, PhD

It's a common misconception that there are no biomarkers available to determine COPD disease status. Both blood eosinophils and fraction exhaled nitric oxide (FeNO) serve as viable, if not each slightly limited, biomarkers in COPD. The real issue is the lack of clinical investigation into more potential biomarkers — an impasse that can delay the development of targeted therapies to treat COPD.

In an interview with HCPLive at the 2025 Global Initiative for Chronic Obstructive Lung Disease (GOLD) International COPD Conference in Philadelphia, PA, this week, Francesca Polverino, MD, PhD, professor of pulmonary medicine at Baylor College of Medicine, reviewed her session presentation on clinical markers of COPD that dictate therapeutic strategy. As Polverino explained, the simplistic measures of COPD type and status are currently robust: blood eosinophils, spirometry-based tests like forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV₁), FeNO , and radiomics help determine a patients’ classification and severity of COPD at any point of assessment.

But a lack of investigation into more promising biomarkers like mucus plugs and club cell protein (CC16) — both of which may help determine a patient’s true response to diverse therapy strategies — stalls targeted therapy development.

“I think [CC16] is next in line,” Polverino said. “All we need is a clinical trial in which CC16 is used prospectively…I think it’s going to be probably the most powerful biomarker in COPD, just because it relates to all patients with COPD, not just a subset of [type 2] COPD patients like eosinophils.”

Polverino referenced very recently published analysis from her and a team of colleagues showing a correlation between lowered CC16 levels and accelerated lung function decline and progression of emphysema. The findings even showed the biomarker’s ability to determine pediatric disease progression: children with lowered levels had correlative obstructive physiology and early small airway impairment.

There has been ample early data supporting the potential of CC16 and mucus plugs in determining COPD status; Polverino wants to see that potential be finally met.

References

1. ^{Rojas-Quintero J, Faner R, Chiu CY, et al. Maternal Smoking and CC-16: Implications for Lung Development and COPD Across the Lifespan. Am J Respir Crit Care Med. Published online October 7, 2025. doi:10.1164/rccm.202504-0854OC}
2. ^{Lugugo N. Dupilumab Reduces Mucus Burden in Uncontrolled Asthma, with Njira Lugogo, MD. HCPLive. Published October 22, 2025. https://www.hcplive.com/view/dupilumab-reduces-mucus-burden-uncontrolled-asthma-njira-lugogo-md}