{
  "abstract": "Introduction Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, associated with inflammation and irreversible lung damage leading to breathlessness. Up to 40% of COPD patients display elevated blood eosinophil counts which are associated with higher exacerbation risks. However, the role eosinophils perform in COPD and heighten exacerbation risk is not understood.Methods Resected background lung tissue was collected from COPD patients (n=26) and non-COPD controls (n=7). COPD samples were stratified based on blood eosinophil count into <200 cells/µL (low) and ≥200 cells/µL (high) COPD subgroups. Eosinophils were phenotyped by flow cytometry using CD62L (resident eosinophil) and CD123 (inflammatory eosinophil) subset markers plus CD63 (cell degranulation), HLA-DR (antigen presentation), and CD11b (cell adhesion) activation markers. Eosinophil peroxidase (EPO) was quantified in cell supernatants by ELISA. Transcriptional analysis of isolated blood eosinophils from non-COPD (n=4) and COPD (n=5) was performed by bulk RNA-sequencing.Results Patient characteristics for non-COPD patients (age: 70.5 ±10.0,%FEV1 pred: 99.2% ±15.8, smoking park years (PY): 34.0 ±12.9, 53.3% male), low eosinophil COPD (age: 68.0 ±9.2,%FEV1pred: 71.0% ±25.9, PY: 36.0 ±24.3, 41.4% male) and high eosinophil COPD (age: 68.5 ±13.0,%FEV1pred: 61.0% ±26.1, PY: 44.0 ±18.2, 69.2% male) showed no statistical differences between COPD subgroups. While eosinophil subset CD62L/CD123 and activation markers CD63/HLA-DR were unaltered, CD11b expression positively correlated with blood eosinophil number (r=0.39, p=0.008; figure 1A). Normalised for cell number, EPO release increased 2.2-fold in eosinophils derived from high eosinophil COPD compared to non-COPD (p=0.037) (figure 1B). Moreover, transcriptional blood eosinophil data demonstrated enrichment for degranulation (padj=2.06E-07), metabolic pathways (padj=0.0002), and DNA repair (padj=0.0005) in COPD blood-derived eosinophils.Abstract T3 Figure 1COPD eosinophil phenotype and function. (A) Flow cytometry analysis of lung-derived eosinophils CD11b+ cellular expression associated with clinical blood eosinophil count (Spearman correlation, blue dots-non-COPD, red dots-COPD). (B) Lung-derived eosinophils normalised to cell number eosinophil peroxide release (Kruskal-Wallis test). Data show median ± IQR. *P ≤ 0.037Conclusion Overall, data suggest primed COPD blood-derived eosinophils enter the lung via more efficient contact-dependant adhesion and migration via CD11b. In high eosinophil COPD patients this facilitates focused localisation of excessive EPO degranulation in the lung.",
  "authors": [
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "SP Cass"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "JR Baker"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "REK Russell"
    },
    {
      "affiliations": [
        "King’s College London, London, UK"
      ],
      "name": "M Bafadhel"
    }
  ],
  "title": "T3 Lung eosinophils in eosinophilic COPD patients differ functionally but not phenotypically",
  "uid": "8072bf35-1009-5740-a5fc-3ddb8d9e88f8"
}