Immunological Basis for Benralizumab Activity in Chronic Obstructive Pulmonary Disease (COPD)

The current literature suggests that the mode of action of benralizumab is to deplete eosinophils through a mechanism of antibody-dependent cell-mediated cytotoxicity. This direct cellular cytotoxicity may not explain all of the benralizumab effects. The investigators propose a set of studies to systematically examine the spectrum of effects of this drug on the immune system.

The investigators will recruit a total of 45 Chronic Obstructive Pulmonary Disease (COPD) participants from the Temple University Hospital Lung Center Clinic. All participants will have moderate to severe COPD and have a history of 2 or more acute exacerbations in the past year. Thirty participants will have eosinophil counts of greater than 220 cells/microliter and 15 participants will have an eosinophil count less than 150 cells/microliter. The 15 participants with eosinophil counts less than 150 cells/microliter will be similar in age, gender, race, and disease burden to the 30 participants in the treatment arms. The investigators studies will include an analysis of the status of the systemic and lung inflammatory phenotype of the major leukocyte populations, using multiparameter flow cytometry. The investigators will couple these studies with an analysis of a panel of inflammatory and anti-inflammatory biomarkers in both the blood and bronchoalveolar lavage fluid. Very importantly, the investigators will characterize the functional capacity of T cells, B cells, monocytes, and granulocytes during drug therapy. These assessments will be linked to a characterization of the immunocompetence of the leukocytes by assessing global transcript dynamics as determined by RNA sequencing (RNAseq). Finally, the investigators will determine the influence of drug treatment by conducting metagenomic sequencing of bacterial, fungal and viral components of the microbiome in these patients. By using this approach, the investigators believe that a more complete understanding of the scope of activity of benralizumab at the level of immune competence will be developed.