Beyond Eosinophils: COPD Biomarkers and Overtreatment Risk

Treatment escalation in patients with chronic obstructive pulmonary disease (COPD) was a key talking point at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain.

There, Francesca Polverino, MD, PhD, a physician-scientist and tenured Lester and Sue Smith Professor of Medicine at Baylor College of Medicine, moderated a session debating how to classify exacerbation severity and what warrants treatment escalation. In an interview with The American Journal of Managed Care^® (AJMC^®), Polverino discussed the biomarkers that could help distinguish a true signal of disease progression from an isolated exacerbation, challenges when defining patients’ susceptibility to worsening airflow limitation, and whether enough research is targeting the risks of overtreatment.

This transcript was lightly edited for clarity.

AJMC: The session aims to distinguish a “signal of progression” from an "isolated event." Based on what we know about the underlying pathology of COPD, do you think there are early biomarkers—beyond eosinophils and symptom scores—that could help make that distinction more reliably?

Polverino: We keep saying that in COPD we don't have biomarkers, but the truth is that we have a lot of biomarkers that have been published in good papers. What we don't have are clinical trials that leverage these biomarkers to better understand how to categorize patients for clinical trials.

For example, one is CC16, club cell protein 16. This is a biomarker that I—and other groups—have confirmed to have decreased low levels of CC16 blood levels and is associated with fast lung function decline in more than 8 COPD cohorts, including in pediatric cohorts. This is an example of how we do have biomarkers available, but what we don't have is clinical trials.

Having said that, these clinical trials are probably not going to be pharma-sponsored clinical trials because they are going to be high risk. They’d have to be more NIH-sponsored clinical trials. But we do have a lot of potential biomarkers, including radiology, for example, mucus plugs. That could be an excellent biomarker for COPD.

And we know from a dupilumab trial that the mucus plugs can change in response to biologics and can also be a biomarker of progression or lack thereof. We do have biomarkers, but we need more clinical trials that can leverage the existing biomarkers to understand more about how to categorize COPD patients and how to track disease progression.

AJMC: As someone who studies why certain individuals are more susceptible to chronic airflow limitation in the first place, how much do you think that susceptibility should shape how aggressively we treat a first exacerbation versus treating all patients under a uniform guideline threshold?

Polverino: The concept of susceptibility is a little controversial. How do you define a susceptible person? Is a susceptible person someone who tends to have a lot of exacerbations or someone who simply has risk factors?

For example, a young patient who has never had an exacerbation before and is GOLD 1 or GOLD 0—I don't know if this person is less susceptible, but they are certainly in better shape to handle an exacerbation than a patient who is GOLD 3 or GOLD 4 and is a 75-year-old with a lot of comorbidities.

We really don't know who is susceptible to getting an exacerbation. What we know is who can handle an exacerbation better than another.

AJMC: Overtreatment and harm are explicitly part of this session's framing. In your experience reviewing grants and research in this space, is there enough investment currently going into understanding the downside risks of early escalation, or is most of the research focus still on undertreatment?

Polverino: We know the side effects of oral corticosteroids and steroids in general. We know that there is a subset of patients with COPD that actually do not benefit from the use of steroids, because the role of steroids is to dampen the inflammation and immune system. And a lot of patients do need that inflammation and immune system because it is good for us, not bad. So we cannot completely wipe out all of our immune cells in order to treat an exacerbation.

We know that, for example, patients with high eosinophils benefit from the use of steroids. However, some patients who don't have the eosinophilic component might not benefit from steroids, and that might not make them ideal candidates for steroid use when it comes to an exacerbation, especially for future response to exacerbation.

We know that there are some immunological factors, like histone deacetylase. For example, these can influence the way you respond to steroids. However, these immune susceptibility factors have not been implemented in clinical practice. So far, we mainly rely on blood eosinophilia when it comes to the use of steroids.

AJMC: Looking at where COPD research is headed, do you think risk stratification after a single exacerbation will eventually be driven by genetic or molecular markers, or will it remain primarily a clinical judgment call based on history and symptoms for the foreseeable future?

Polverino: For the foreseeable future—if you tell me 10 years from now, I can see how the patient with COPD will be stratified based on blood biomarkers or other accessible biomarkers, like sputum or CT scan biomarkers, with what we call multi-omic integration. This is a multi-scale integration of omics technologies, which can be proteomics, breathomics, or radiomics—all these technologies that are now in the works and have been assessed by research teams like mine will eventually be validated and integrated.

But again, we do need clinical trials that can leverage these existing biomarkers to see whether they can better help us categorize the patient for future trials and for the clinical management of COPD.