Currently available biomarkers can help clinicians care for patients with chronic obstructive pulmonary disease (COPD). Recent data offer insights into how biomarker measurement in patients with COPD can be applied in clinical practice to help predict risk of exacerbations and mortality, as well as to assess potential treatment response.

COPD is heterogeneous, with different underlying pathophysiologic pathways and external phenotype manifestations. Biomarkers can help identify clinically meaningful subtypes that may not be apparent from spirometry alone.

Plasma fibrinogen is the only currently US Food and Drug Administration (FDA)–approved biomarker that has been shown to predict risk of exacerbations and mortality in patients with COPD. However, its performance characteristics are modest and nonspecific, and, therefore, plasma fibrinogen is not widely used in clinical practice or trials.

We now appreciate the role of type 2 inflammation in COPD, and blood eosinophils may be a good biomarker for this. Once type 2 inflammation is identified, it can be targeted for treatment. Blood eosinophils can also help predict response to therapy and risk of exacerbations, but only in patients who have a history of exacerbations.

A blood eosinophil count of at least 100 cells/μL predicts a response to ICS therapy. The recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) document indicates that patients with eosinophil counts of 300 cells/μL or higher and patients with eosinophil counts of 100 cells/μL or higher and persistent COPD exacerbations with uncontrolled symptoms on LAMA/LABA maintenance therapy are candidates for triple therapy with an ICS, a LABA, and a LAMA. In patients with eosinophil counts of 300 cells/μL or higher who continue to have exacerbations despite triple therapy, biologics can be added to target type 2 inflammation.

It is important to note that blood eosinophil levels can fluctuate and can be affected by systemic steroid therapy. So, if a patient with COPD receives intravenous or oral steroids, it is recommended to wait a few weeks before measuring their eosinophils. It is also recommended to check eosinophil counts often because a single low value is not enough to confirm the absence of type 2 inflammation. If levels are consistently low, then one can more confidently assume that the patient does not have type 2 inflammation. Now that there are good therapies for type 2 inflammation, it is important to have a high index of suspicion and actively test for it.

Fractional exhaled nitric oxide (FeNO) can also be an indicator of type 2 inflammation. FeNO is already in widespread use to measure asthma control. When the FeNO level is less than 10 parts per billion, one can assume that type 2 inflammation and asthma are reasonably well controlled. In COPD, this can become tricky because many people with COPD continue to smoke, which can decrease FeNO levels.

Another biomarker is IgE, which is associated with a higher frequency of exacerbations. Finally, some studies have used the neutrophil-lymphocyte ratio, which is associated with a higher exacerbation risk, but this provides modest differentiation. Further, the cutoffs have been variable from study to study, with no consensus on where they should fall.