The Role of Eosinophils as a Biomarker to Inform Treatment Decisions for Patients With COPD

There are many diagnostic, prognostic, and treatment challenges in managing patients with chronic obstructive pulmonary disease (COPD), as the pathogenesis of COPD is convoluted, and many knowledge gaps remain in the underlying cellular and molecular mechanisms. Blood eosinophil count is becoming increasingly recognized by the respiratory specialist community as a clinically relevant biomarker to help estimate effective management strategies, but its use is still widely debated.

Nathaniel Marchetti, DO, answers questions about the role of eosinophils as a biomarker to inform treatment decisions for patients with COPD. Dr Marchetti is a pulmonologist with Temple Lung Center and a professor of clinical thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University.

Consultant360: What is the threshold for defining high and low eosinophil blood count?

Dr Nathaniel Marchetti: Most clinicians would consider a blood eosinophil count greater than 300 cells/μL to be elevated.¹ In in patients with COPD, there is not a low or high threshold for eosinophil counts. It can be thought of as a spectrum, with those having an eosinophil count less than 100 cells/μL unlikely to respond to inhaled corticosteroids (ICS) and those with an eosinophil count greater than 300 cells/μL more likely to respond.¹ Most clinicians would agree that an eosinophil count greater than 300 cells/μL would indicate a response to ICS. It is important to understand that this is not the only factor involved in deciding when to use ICS, and other factors, such as exacerbation frequency, need to be considered as well.

C360: Approximately what percentage of patients with COPD have evidence of eosinophilic inflammation?

NM: This question is difficult to answer. However, it appears as though individuals with COPD have more eosinophils in their blood compared with the rest of the population. Some studies estimate that 20.1% of patients with COPD will have an eosinophil count greater than 300 cell/μL.²

C360: What role do eosinophils play in COPD during exacerbations and stable disease?

NM: It appears patients with higher blood eosinophil levels during stable disease have more frequent exacerbations and are likely to respond better to systemic corticosteroids.³

C360: What role might eosinophils play as a biomarker to inform treatment decisions for patients with COPD?

NM: Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines¹ suggest that inhaled corticosteroids (ICS) should be used in those with an eosinophil count greater than 300 cells/μL. However, this is not the only factor. If patients have more than 2 moderate exacerbations per year, they should be on an ICS regardless of eosinophil count. For those with blood eosinophils of 100 or greater, an inhaled corticosteroid can be considered. If the eosinophil count is less than 100/μL, then ICS is not likely going to benefit patients.⁴  

C360: What therapies targeting eosinophilic inflammation are available or in development?

NM: Inhaled corticosteroids are available and important in targeting eosinophilic inflammation in patients with COPD.

Biologic agents targeting eosinophilic inflammatory pathways have been studied with mixed results. These studies have targeted the ability of these medications to reduce exacerbations of COPD. Currently, it is not recommended to use these agents in COPD until better data are available. There are clinical trials ongoing with these medications to determine if they can help reduce exacerbations. Targeted pathways include IL-5, anti-TSLP, IL-33, IL-25. All of these are important in eosinophilic inflammation.⁴

C360: What gaps exist in the research of patients with COPD and eosinophilic inflammation? And what is next for research?

NM: Eosinophil counts vary over time. We do not entirely understand how they vary and the meaning of the variation. As mentioned, there are numerous inflammatory pathways that can be targeted to help with eosinophilic inflammation, and there are medications in development and clinical trials to find if they can help.⁴

References:

1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for prevention, diagnosis, and management of COPD: 2022 report. Accessed August 29, 2022. www.goldcopd.org/2022-gold-reports-2/
2. Singh D, Wedzicha JA, Siddiqui S, et al. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020;21(1):240. doi:10.1186/s12931-020-01482-1
3. Oliver B, Tonga K, Darley D, et al. COPD treatment choices based on blood eosinophils: are we there yet? Breathe (Sheff). 2019;15(4):318-323. doi:10.1183/20734735.0254-2019
4. Harries TH, Rowland V, Corrigan CJ. Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. Respir Res. 2020;21(1):3. doi:10.1186/s12931-019-1268-7