{
  "abstract": "Introduction The current cystic fibrosis (CF) care era, while hugely welcome, raises new challenges, particularly the need for more sensitive pulmonary outcome measures. Seeking further optimisation, we previously developed a Short extension to multiple breath washout measure (MBW ShX) which captures previously overlooked, under-ventilated lung units but lacks regional information. Functional lung MRI addresses this limitation. We hypothesised these measures would be more sensitive to change in tracking CF lung disease than usual clinical respiratory function tests.Methods Forty-six people with (pw)CF, median age 15 (range 6–55) years were recruited to a single-centre study. While clinically stable, pwCF performed OE-MRI, MBW+/- ShX and spirometry at baseline and at 6 monthly intervals over 18 months of follow-up. A subgroup of pwCF (n=20) and age-matched healthy controls (HC, n=20) performed two repeatability visits within 6 weeks.Results OE-MRI/MBW ShX were well tolerated, differentiated HC and CF groups, and were repeatable with negligible differences between two visits <6 weeks apart. OE-MRI/MBWShX parameters worsened at 12 months (p<0.05) and 18 months (p<0.01). In contrast, conventional measures of pulmonary function (FEV1+ LCI2.5) did not change significantly.Conclusions OE-MRI/MBW ShX are novel, sensitive tools to track progression of abnormalities in lung structure/function. Such progression may not be detected by conventional outcome measures. CF transmembrane conductance regulator (CFTR) modulators have been transformative for many pwCF and generally lead to substantial improvements in lung health. Stable FEV1 over longer time periods and, during mucoactive treatment withdrawal, may give false reassurance. OE-MRI/MBWShX reveal the likely less welcome reality that lung-disease progresses despite CFTR modulators. These measures could be considered in future studies when enhanced sensitivity is required.",
  "authors": [
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, England, UK",
        "Royal Brompton and Harefield Hospitals, Guy's and St Thomas’ Hospitals NHS Trust, London, England, UK",
        "Lung Clearance Index Core Facility, European Cystic Fibrosis Society, London, UK"
      ],
      "name": "Christopher Short"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, England, UK",
        "Royal Brompton and Harefield Hospitals, Guy's and St Thomas’ Hospitals NHS Trust, London, England, UK",
        "Centre for Paediatrics and Child Health, Imperial College London, London, England, UK"
      ],
      "name": "Tom Semple"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, England, UK",
        "Royal Brompton and Harefield Hospitals, Guy's and St Thomas’ Hospitals NHS Trust, London, England, UK",
        "Lung Clearance Index Core Facility, European Cystic Fibrosis Society, London, UK"
      ],
      "name": "Mary Abkir"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, England, UK"
      ],
      "name": "Constantinos Efthyvoulou"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, England, UK",
        "Royal Brompton and Harefield Hospitals, Guy's and St Thomas’ Hospitals NHS Trust, London, England, UK"
      ],
      "name": "Simon Padley"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, England, UK",
        "Royal Brompton and Harefield Hospitals, Guy's and St Thomas’ Hospitals NHS Trust, London, England, UK"
      ],
      "name": "Mark Rosenthal"
    },
    {
      "affiliations": [
        "Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland",
        "Department of Respiratory Medicine, Children’s Health Ireland, Dublin, Ireland"
      ],
      "name": "Paul McNally"
    },
    {
      "affiliations": [
        "Department of Paediatric Pulmonology and Allergology, Erasmus MC -Sophia Children’s Hospital, Rotterdam, Netherlands",
        "Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, Netherlands",
        "Thirona, Rotterdam, Netherlands"
      ],
      "name": "Harm Tiddens"
    },
    {
      "affiliations": [
        "Department of Paediatric Pulmonology and Allergology, Erasmus MC -Sophia Children’s Hospital, Rotterdam, Netherlands",
        "Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, Netherlands"
      ],
      "name": "Daan Caudri"
    },
    {
      "affiliations": [
        "Bioxydyn Ltd, Manchester, UK"
      ],
      "name": "Marta Tibiletti"
    },
    {
      "affiliations": [
        "Bioxydyn Ltd, Manchester, UK",
        "Department of Medical Physics & Biomedical Engineering, University College London, London, England, UK"
      ],
      "name": "Geoff J Parker"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College London, London, England, UK",
        "Royal Brompton and Harefield Hospitals, Guy's and St Thomas’ Hospitals NHS Trust, London, England, UK",
        "Lung Clearance Index Core Facility, European Cystic Fibrosis Society, London, UK",
        "Centre for Paediatrics and Child Health, Imperial College London, London, England, UK"
      ],
      "name": "Jane Carolyn Davies"
    }
  ],
  "title": "Oxygen-enhanced MRI and multiple breath washout with Short extension reveal cystic fibrosis lung disease progression despite triple modulator therapy",
  "uid": "44f6e6eb-71da-5201-8088-f75376497b63"
}