Review: Unclear Whether Eosinophilic COPD Contributes to Pathogenesis of COPD

The role that eosinophilic chronic obstructive pulmonary disease (COPD) plays in the pathogenesis of COPD is not well understood, given the lack of evidence about the subject.

A review focusing on the mechanisms of eosinophilia in chronic obstructive pulmonary disease (COPD), the utility and specificity of eosinophilia in this patient population, and the data currently available that might validate an approach to eosinophilic COPD determined that the evidence that eosinophilic COPD constitutes a distinct subset of COPD remains unclear.

Observations from the review were published in Lung.

Eosinophils come from CD34+ precursor cells, which are the common precursor for eosinophils and basophils. In the blood, eosinophils have a circulatory time of 8 to 18 hours before being incorporated into a variety of tissues including the gastrointestinal tract, the uterus, thymus, and, in some disease states, lung.

A variety of definitions of peripheral blood eosinophilia have been used in the context of COPD, including the currently accepted definition of having an eosinophil count greater than 2% of total cells or more than 150 total cells/mcL.

Past research has demonstrated that as a single variable, eosinophilia is associated with poorer outcomes in COPD. The relationship between eosinophilia in COPD and response to corticosteroids could be an important determinant as to whether a distinct population of COPD patients can be defined by the presence of eosinophilia, as previous research has shown that the association of poorer outcomes in eosinophilic asthma appears strong for patients who are clinically resistant to corticosteroids.

Studies involving anti–interleukin (IL)-5 therapies demonstrated that they were effective in significantly reducing the number of eosinophils in blood and sputum in patients with asthma but were ineffective in improving asthma outcomes. Past data regarding anti–IL-5 therapy may suggest that with proper patient selection, a highly specific group of patients with COPD might benefit from anti–IL-5 therapy or that the number needed to treat for IL-5 therapies in COPD is quite high such that individual studies had insufficient power to detect a difference.

Although proven to be successful in reducing eosinophilia, the failure of anti–IL-5 therapies to affect COPD exacerbation rate in most individual studies weakens the idea that eosinophilia plays an integral role in the morbidity of COPD.

Dupilumab, a fully human immunoglobulin G4 monoclonal antibody directed against the IL-4 R-alpha subunit, has been shown to significantly improve asthma control, airflow, and symptom improvement in patients with asthma regardless of the presence of baseline peripheral blood eosinophilia. A pivotal study to assess the efficacy, safety, and tolerability of dupilumab in patients with moderate to severe COPD with type 2 inflammation is underway.

Unlike asthma, in which the immunologic mechanisms of atopic disease and eosinophilia are linked with an increasing eosinophil count and poor control of the disease, there is little evidence to determine that eosinophilia contributes to the pathogenesis of severe COPD, authors concluded.

Reference

Weissler JC, Adams TN. Eosinophilic chronic obstructive pulmonary disease. Lung. 2021;199(6):589-595. doi:10.1007/s00408-021-00492-0