{
  "abstract": "Background Mepolizumab, an anti-IL-5 biologic used to treat T2 high severe asthma (T2 high SA), reduces exacerbation and improves asthma control. Airway remodelling is associated with persistent symptoms and lung function decline. Limited evidence exists investigating the effect of mepolizumab on airway remodelling.Objective We aimed to investigate the effect of mepolizumab treatment on airway remodelling in patients with T2 high SA, hypothesising a reduction in airway remodelling markers and an increase in epithelial barrier repair following 6 months of treatment.Methods Bronchial biopsies from 20 patients with T2 high SA were collected by bronchoscopy at baseline (T0) and 6 months (T6) post mepolizumab treatment ( NCT05144087, GSK funded, investigator led study). Fourteen (70%) paired biopsies were analysed using immunohistochemistry (IHC) and movat’s pentachrome staining. Clinical and lung function data were also collected.Results At T6, there was a significant reduction in exacerbations (median AER: T0 5 [IQR 4–7], T6 0 [0,0]) and significant improvement in asthma control (ACQ: T0 2.8 [IQR 2.1,3.1], T6 1.0 [0.3,2.1]) and lung function (FEV1/FVC: T0 0.60 [IQR 0.57, 0.66], T6 0.64 [IQR 0.58,0.75]). In bronchial biopsies, submucosal eosinophil counts were significantly reduced ( P ≤ 0.05) along with markers of remodelling including extracellular matrix deposition of collagen and elastin (both P ≤ 0.001, by movat’s pentachrome) and collagen I (P ≤ 0.05, by IHC). Basement membrane thickness was also significantly reduced (mean T0 6.6 mm [0.3], T6 5.7 mm [1.1], p=0.04). Finally, in the bronchial epithelium there was a reduction in goblet cells (P ≤ 0.01) and a significant increase in e-cadherin (a component of adherens junctions) (P ≤ 0.0001).Conclusions In patients with T2 high SA, mepolizumab treatment significantly reduced airway inflammation and structural markers of airway remodelling including submucosal eosinophils, extracellular matrix components and basement membrane thickness. Notably, our study is the first to demonstrate improved epithelial barrier integrity with biologic therapy in T2 high SA, as evidenced by increased e-cadherin expression. These findings suggest that, beyond clinical improvements, mepolizumab reverses key features of airway remodelling in patients with T2 high SA.",
  "authors": [
    {
      "affiliations": [
        "University of Southampton, Southampton, UK"
      ],
      "name": "I Drummond"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK"
      ],
      "name": "J Phillips"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK"
      ],
      "name": "R Dhillon"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK"
      ],
      "name": "A Eminton"
    },
    {
      "affiliations": [
        "University Hospital Southampton, Southampton, UK"
      ],
      "name": "J Naftel"
    },
    {
      "affiliations": [
        "University Hospital Southampton, Southampton, UK"
      ],
      "name": "W Soe"
    },
    {
      "affiliations": [
        "University Hospital Southampton, Southampton, UK"
      ],
      "name": "P Dennison"
    },
    {
      "affiliations": [
        "Kings College London, London, UK"
      ],
      "name": "RT Martinez-Nunez"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK"
      ],
      "name": "L Lau"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK"
      ],
      "name": "J Ward"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK",
        "NIHR Southampton Biomedical Research Centre, Southampton, UK"
      ],
      "name": "C Blume"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK",
        "NIHR Southampton Biomedical Research Centre, Southampton, UK"
      ],
      "name": "EJ Swindle"
    },
    {
      "affiliations": [
        "University of Southampton, Southampton, UK",
        "University Hospital Southampton, Southampton, UK",
        "NIHR Southampton Biomedical Research Centre, Southampton, UK"
      ],
      "name": "H Rupani"
    }
  ],
  "title": "T5 Reduced airway remodelling and increased epithelial barrier integrity in bronchial biopsies from patients with T2 high severe asthma following mepolizumab treatment",
  "uid": "b65cd2f1-7c61-5107-bfb8-20d8530cbcb1"
}