Copd_a_198302 1177..1185

Introduction Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and airway inflammation. Although typically neutrophilic, COPD is eosinophil-predominant in 10%‒40% of cases. Increased airway or blood eosinophil counts are associated with a good response to corticosteroids in stable COPD and during exacerbations. Interleukin-5 (IL-5) binds with high affinity to the IL-5 receptor (R) alpha (IL-5Rα) subunit and plays a pivotal role in the differentiation andmaturation of eosinophils in the bone marrow and their survival in tissue. In a 1-year randomized placebo-controlled trial of benralizumab, a humanized, afucosylated, monoclonal antibody that inhibits IL-5Rα activation and promotes antibody-dependent cellmediated cytotoxicity (leading to near complete eosinophil depletion), improvements in lung function and symptoms and reduction in exacerbations were observed in patients with eosinophilic inflammation. However, in non-eosinophilic COPD patients, exacerbation frequency increased following benralizumab treatment vs placebo. Likewise, in a 6-month trial, the IL-5 neutralizing monoclonal antibody mepolizumab reduced exacerbations vs placebo in COPD patients with an increased blood eosinophil count but resulted in a greater exacerbation frequency in those with a low blood eosinophil count. This finding contrasts with that for asthma for which absence of eosinophilic inflammation is associated with neither benefit nor harm to anti‒IL-5(R). Interestingly, the airway microbiome is distinct between COPD patients with vs those without eosinophilic inflammation. Corticosteroid therapy alters the airway microbiome and consequently might hinder recovery during exacerbations in patients without eosinophilic inflammation. Whether this exacerbation relationship to low eosinophil count is genuine and these effects are partly because of attenuation of Correspondence: Christopher E Brightling University of Leicester, Glenfield General Hospital, Leicester, LE3 9QP, UK Tel +44 116 258 3998 Fax +44 116 25