{
  "abstract": "Background Despite significant clinical improvements, there is evidence of persisting airway inflammation in people with cystic fibrosis (CF) established on elexacaftor/tezacaftor/ivacaftor (ETI) therapy. As CF is a multi-system disease, systemic immune profiles can reflect local inflammation within the lungs and other organs. Understanding systemic inflammation after ETI therapy may reveal important translational insights. This study aims to profile systemic inflammatory changes and relate these to the well-documented improvements observed with ETI therapy.Methods We conducted a single-centre longitudinal study with 57 CF subjects initiating ETI therapy. All participants were Phe508del homozygous or Phe508del/minimal function. Blood samples were collected pre-ETI and 3–12 months post-therapy initiation. Analyses included mass spectrometry-based proteomics, a multiplex immunoassay, and flow cytometry for peripheral immune cell counts and phenotype. Controls samples were provided by 29 age-matched healthy controls.Results Systemic inflammation reduced with ETI therapy; however, the immune profile remained distinct from healthy controls. ETI reduced neutrophil counts and was associated with a more mature, less inflammatory phenotype, as well as a shift towards an immune resolving state associated with increased CD206 expression. Cytokines known to influence neutrophil levels reduced with therapy. Despite ETI therapy, neutrophil and monocyte counts remained elevated compared with healthy controls. There was no obvious association between the ETI-related improvements in systemic inflammation and lung function.Conclusions Patients with CF showed evidence of persisting systemic inflammation despite ETI therapy, which may have long-term potentially adverse effects on respiratory and other organ systems.",
  "authors": [
    {
      "affiliations": [
        "Centre for Proteome Research, Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK"
      ],
      "name": "Rosemary E Maher"
    },
    {
      "affiliations": [
        "Lydia Becker Institute for Immunology and Inflammation, University of Manchester, Manchester, UK",
        "Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK",
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK"
      ],
      "name": "Urszula M Cytlak-Chaudhuri"
    },
    {
      "affiliations": [
        "Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Saad Aleem"
    },
    {
      "affiliations": [
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK",
        "Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK",
        "Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Peter Barry"
    },
    {
      "affiliations": [
        "Lydia Becker Institute for Immunology and Inflammation, University of Manchester, Manchester, UK",
        "Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK",
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK"
      ],
      "name": "Daniel Paul Brice"
    },
    {
      "affiliations": [
        "Computational Biology Facility, Liverpool Shared Research Facilities, Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK",
        "Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK"
      ],
      "name": "Eva Caamaño Gutiérrez"
    },
    {
      "affiliations": [
        "Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Kimberley Driver"
    },
    {
      "affiliations": [
        "Centre for Proteome Research, Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK",
        "Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK"
      ],
      "name": "Edward Emmott"
    },
    {
      "affiliations": [
        "Computational Biology Facility, Liverpool Shared Research Facilities, Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK",
        "Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK"
      ],
      "name": "Alexander Rothwell"
    },
    {
      "affiliations": [
        "Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Emily Smith"
    },
    {
      "affiliations": [
        "Lydia Becker Institute for Immunology and Inflammation, University of Manchester, Manchester, UK",
        "Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK",
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK"
      ],
      "name": "Mark Travis"
    },
    {
      "affiliations": [
        "Lydia Becker Institute for Immunology and Inflammation, University of Manchester, Manchester, UK",
        "Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK",
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK"
      ],
      "name": "Dave Lee"
    },
    {
      "affiliations": [
        "Department of Child Health (University of Liverpool), Institute in the Park, Alder Hey Children's Hospital, Liverpool, UK"
      ],
      "name": "Paul Stephen McNamara"
    },
    {
      "affiliations": [
        "Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Ian Waller"
    },
    {
      "affiliations": [
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK",
        "Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Jaclyn Ann Smith"
    },
    {
      "affiliations": [
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK",
        "Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK",
        "Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Andrew Jones"
    },
    {
      "affiliations": [
        "Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK",
        "Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK",
        "Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "Robert W Lord"
    }
  ],
  "title": "Effect of elexacaftor/tezacaftor/ivacaftor on systemic inflammation in cystic fibrosis",
  "uid": "9686a1e6-4807-5db1-9bd6-215528778324"
}