Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

Abstract

COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD.

Keywords: asthma; corticosteroids; lung disease; pneumonia; pulmonary diseases.

Figure 1

Eosinophil trafficking from bone marrow to airway. Notes: Eosinophil activity occurs in tissue. Mature eosinophils leave bone marrow, circulate in blood, and migrate to tissue under the influence of various chemotactic factors. Infiltration into the airways is mediated through adhesion and transmigration across the bronchial vascular epithelium. Chemokines, such as CCL5 and CCL11, and other factors play roles in this process. Reprinted with permission of Sage Publications, Ltd. George L, Brightling CE. Therapeutic Advances in Chronic Disease. 2016;7(1):34–51, Copyright 2016. Abbreviation: GM-CSF, granulocyte-macrophage colony-stimulating factor.

Figure 2

Hospital admissions due to exacerbations in COPD patients treated to optimize symptoms alone or in combination with minimizing eosinophil counts. Notes: Patients treated to optimize symptoms only (□; n=11); and those treated to optimize symptoms and minimize airway eosinophil inflammation (minimize eosinophilia, keeping sputum eosinophil at <3%) (•; n=12). For patients in the optimize symptoms only group, the hierarchy of treatment was short-acting β_2-agonist, regular anticholinergic, LABA, LAMA, theophylline, and then a trial with a nebulizer; inhaled corticosteroids continued at the same dosage if the patient was already receiving them. For patients in the optimize symptoms and minimize sputum eosinophils group, treatment hierarchy was the same as above. However, patients received the smallest appropriate dosage of anti-inflammatory treatment (ICS or oral CS) to keep sputum eosinophil counts <3%; if eosinophil counts were >3%, then anti-inflammatory treatment was increased. Reproduced with permission of the European Respiratory Society from Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29(5):906–913. [Disclaimer: This material has not been reviewed prior to release; therefore, the European Respiratory Society may not be responsible for any errors, omissions, or inaccuracies, or for any consequences arising there from, in the content.] Abbreviations: CS, corticosteroid; ICS, inhaled corticosteroid; LABA, long-acting β-agonist; LAMA, long-acting muscarinic antagonist.