{
  "abstract": "Introduction For the majority of people with cystic fibrosis (pwCF), the initiation of highly effective modulator therapy (HEMT) has led to improvements in FEV1. FEV1 does not however assess ventilation heterogeneity and historically has lacked sensitivity to detect lung damage. 129Xe-MRI directly images ventilation heterogeneity in 3D and is highly sensitive to lung damage. Here we aimed to assess the change in lung function using 129Xe-MRI and pulmonary function tests in a historical cohort of pwCF taking HEMT.Methods Eighteen pwCF (M=10, F=8) were assessed twice ~5.7 (SD 0.45) years apart using 129Xe-MRI, spirometry, body plethysmography and multiple-breath washout to calculate lung clearance index (LCI). Ventilation defect percentage (VDP) from 129Xe-MRI was calculated as the proportion of the lung without ventilation. HEMT was initiated at a variable time point for pwCF prior to re-assessment. Longitudinal change was assessed using paired t-tests or Wilcoxon signed-rank tests. Data are presented as mean (SD) or median [IQR].Results Baseline, age, height and weight = 24.2 (11.7)years, 159.9 (11.2)cm and 53.8 (13.05)kg. Follow-up age, height and weight= 29.9 (11.6)years, 167.9 (9.2)cm and 66.5 (9.5)kg.At baseline (pre-HEMT), on average pwCF had significant lung disease, with reduced FEV1 Z-score = -2.30 [-3.61,-0.16]z, FEV1/FVC = -2.65 (1.47)z, and increased RV/TLC = 2.71 [0.37,3.85]z and LCI = 10.0 [7.17,13.7]. Xe-MRI showed numerous, often large ventilation defects and an increased VDP (19.7 [3.50,38.8])%. At follow-up, on average, FEV1 improved (p=0.0001, median difference (md) = 0.45z, CI=0.25,0.81)z, however FEV1/FVC was unchanged. RV/TLC also improved (p=0.0008, md = -0.69z, CI = -1.29,-0.1)z. In contrast, for ventilation heterogeneity metrics, on average, there was a worsening in LCI (p= 0.027, md = 0.91, CI= 0.06,3.23) and no change in VDP, with ventilation defects mostly persisting (figure 1).Conclusions After a lengthy follow-up period and the initiation of HEMT, pwCF have improved FEV1 and reduced gas trapping. Despite this, there is discordance between these improved volume-based metrics and those assessing airflow limitation (FEV1/FVC) and ventilation heterogeneity (VDP and LCI), which largely remain unchanged. People with CF therefore still have significant lung function abnormalities which Xe-MRI can regionally locate within the lung.129Xe-MRI images from two pwCF (A and B) at baseline (top row) and follow-up (bottom row). Areas that appear grey and white on the images are areas of increased signal intensity from the 129Xe gas and represent regions of lung ventilation. Areas of the image that appear black are areas where the 129Xe gas is unable penetrate due to lung disease. These areas are termed ventilation defects and are quantified using ventilation defect percentage (VDP), which is the proportion of the lung without ventilation. Both pwCF had an improvement in FEV1 at follow-up, with limited change in FEV1/FVC and a worsening LCI. Persistent ventilation defects are seen in both pwCF with a worsening in VDP at follow-up.Abstract O4 Figure 1129Xe ventilation magnetic resonance imaging (129Xe-MRI) images from two people with cystic fibrosis (pwCF) at baseline and follow-up",
  "authors": [
    {
      "affiliations": [
        "POLARIS, University MRI, Division of Clinical Medicine, University of Sheffield, Sheffield, United Kingdom"
      ],
      "name": "Demi Jakymelen"
    },
    {
      "affiliations": [
        "POLARIS, University MRI, Division of Clinical Medicine, University of Sheffield, Sheffield, United Kingdom"
      ],
      "name": "Laurie Smith"
    },
    {
      "affiliations": [
        "POLARIS, University MRI, Division of Clinical Medicine, University of Sheffield, Sheffield, United Kingdom"
      ],
      "name": "Jim Wild"
    }
  ],
  "title": "O4 Assessing longitudinal change in lung function using 129Xe-MRI and pulmonary function testing in cystic fibrosis",
  "uid": "bfff8214-1ccb-591a-9764-15a08ad53dc8"
}