{
  "abstract": "Background Familial Pulmonary Fibrosis (FPF) manifests when ≥2 family members have idiopathic pulmonary fibrosis or another interstitial lung disease (ILD). With advancements in precision and genomic medicine, there is wider scope to support the care of probands and their first-degree relatives.Aim To assess the role of a dedicated FPF clinic and Multidisciplinary Team (MDT) discussion, involving national and international expertise, to optimise management of probands with suspected genetic predisposition and identifying first-degree relatives at risk of developing ILD.Methods Prospective data were collected from December 2024 to June 2025 for patients attending our FPF service in the UK. We analysed baseline demographics, clinical and functional characteristics, FPF genetic results ( table 1) and MDT outcomes.Results A total of 51 patients were seen through our FPF service, with 50 patients (98%) consenting for the R421-FPF gene panel (nhsgms-panelapp.genomicsengland.co.uk/panels/1174/v1.3). Forty probands (78%) had family history of ILD, with 49 (96%) having living first-degree relatives ≥40 y/o without ILD. Per proband, the median of first-degree relatives was 2 (range 0 – 8). Of the total cohort, 31% of the total cohort (16/51) had first-degree relatives with clinical features suggestive of telomere biology disorders.Up to June-2025, 25 genetic results were received (50% of the consenting cohort), with an average reporting time of 5 months; 12% (3/25) had pathogenic/likely pathogenic variants and 24% (6/25) had Variants of Uncertain Significance (VUS). 52% (13/25) of all results have been discussed in the FPF MDT with 46% (6/13) of all probands being referred to Clinical Genetics services, 23% for Telomere Length testing and consideration of VUS reclassification, and 15% to another specialist service (Hepatology). For the first-degree relatives, 31% (4/13) were referred to Clinical Genetics services and 15% to specialist services (Respiratory/ILD) as per MDT consensus.Abstract S156 Table 1Demographic, clinical, functional, and genetic characteristics of patients with ILD and suspected genetic predisposition evaluated in our Regional Familial Pulmonary Fibrosis Service Characteristics N=51 Demographic Age in years, mean (±SD) 65.7 (12.5) Male, n (%) Female, n (%) 25 (49.1)26 (50.9) Referring Centre in the United Kingdom: • South West Peninsula, England, n (%)• Other regions, n (%) 40 (78.4)11 (21.6) Family history of ILD 40 (78.4) Clinical ILD diagnosis: • Idiopathic Pulmonary Fibrosis, n (%)• Idiopathic non-specific interstitial pneumonia, n (%)• Hypersensitivity pneumonitis, n (%)• Connective tissue disease associated with ILD, n (%)• Unclassifiable ILD, n (%)• Pleuroparenchymal fibroelastosis, n (%)• Other, n (%) 31 (60.8)1 (1.9)6 (11.8)2 (3.9)3 (5.9)3 (5.9)5 (9.8) Lung function FVC - percent predicted, mean (±SD) 77.6 (21.1) DLCO - percent predicted, mean (±SD) 54.0 (15.4) Genetic testing R421 Familial Pulmonary Fibrosis criteria*, n (%)1) Idiopathic ILD <50 y/o2) Family history of ILD3) Suspected telomerase complex mutations/Telomere Biology Disorder4) More than one R421 criteria (e.g. 1+2, 1+3, 2+3) 6 (11.8)35 (68.6)4 (7.8)6 (11.8) Available results -R421 gene panel, n (% of total consenting cohort) 1. No pathogenic variant detected2. Pathogenic/likely pathogenic variant, n (% of 25 available results)3. VUS, n (% of 25 available results)# 4. Risk allele (MUC5B gene)# 25 (50.0)6 (24.0)3 (12.0)6 (24.0)10 (40.0) Type of gene affected (% of 25 available results) 5. Telomere-related gene variant, n (% of 25 available results)6. Surfactant-related gene variant, n (% of 25 available results) 9 (36.0)0 (0.0) Legend: ILD=interstitial lung disease; FVC=forced vital capacity; DLCO=diffusing capacity of the lungs for carbon monoxide; SD= standard deviation; VUS=variant of uncertain significance.*https://www.england.nhs.uk/wp-content/uploads/2018/08/rare-inherited-disease-eligibility-criteria-v8.0.pdf (National Genomic Test Directory, latest version: v8.0 May 2025, Page 372 – R421 testing criteria). #For primary R421 gene panel results; however, three probands had multiple variants identified.Conclusion Over the initial 6-month service evaluation, we identified a high prevalence of first-degree relatives potentially at risk of developing ILD through our dedicated FPF MDT. Further regional and national referrals will likely emphasize this unmet clinical need and support development of a formal NHS pathway/screening programme for first-degree relatives at risk of developing ILD.",
  "authors": [
    {
      "affiliations": [
        "Exeter South West Peninsula Interstitial Lung Disease Service, Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"
      ],
      "name": "C Crook"
    },
    {
      "affiliations": [
        "Exeter South West Peninsula Interstitial Lung Disease Service, Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"
      ],
      "name": "V Elworthy"
    },
    {
      "affiliations": [
        "Exeter South West Peninsula Interstitial Lung Disease Service, Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"
      ],
      "name": "SC Stanel"
    },
    {
      "affiliations": [
        "Clinical Genetics Service, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK",
        "Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"
      ],
      "name": "H Hanson"
    },
    {
      "affiliations": [
        "Clinical Genetics Service, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK",
        "Faculty of Health and Life Sciences, University of Exeter, Exeter, UK"
      ],
      "name": "M Bradford"
    },
    {
      "affiliations": [
        "Sheffield Diagnostic Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK"
      ],
      "name": "D Baker"
    },
    {
      "affiliations": [
        "Haematology Service, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"
      ],
      "name": "T Coats"
    },
    {
      "affiliations": [
        "Exeter South West Peninsula Interstitial Lung Disease Service, Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK",
        "Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"
      ],
      "name": "A Duckworth"
    },
    {
      "affiliations": [
        "Clinical Genetics Service, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"
      ],
      "name": "J Fasham"
    },
    {
      "affiliations": [
        "Hepatology Service, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"
      ],
      "name": "B Hudson"
    },
    {
      "affiliations": [
        "Haematology Service, Kings College of London, London, UK"
      ],
      "name": "A Kulasekararaj"
    },
    {
      "affiliations": [
        "Immunology Service, Auckland District Health Board, Auckland, New Zealand",
        "Trustee, DC Action Charity, London, UK"
      ],
      "name": "H Longhurst"
    },
    {
      "affiliations": [
        "Clinical Genetics and Genomics Laboratory, Royal Brompton Hospital, London, UK"
      ],
      "name": "D Morris-Rosendahl"
    },
    {
      "affiliations": [
        "Regional Interstitial Lung Disease Service, Royal Brompton Hospital, London, UK"
      ],
      "name": "E Renzoni"
    },
    {
      "affiliations": [
        "Exeter South West Peninsula Interstitial Lung Disease Service, Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK",
        "Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK"
      ],
      "name": "CJ Scotton"
    },
    {
      "affiliations": [
        "Exeter South West Peninsula Interstitial Lung Disease Service, Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK",
        "Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK",
        "NIHR Exeter Biomedical Research Centre, University of Exeter, Exeter, UK"
      ],
      "name": "MA Gibbons"
    },
    {
      "affiliations": [
        "Exeter South West Peninsula Interstitial Lung Disease Service, Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"
      ],
      "name": "P Rivera-Ortega"
    }
  ],
  "title": "S156 Targeted clinical management of probands and at-risk relatives in familial pulmonary fibrosis: a regional model with national relevance",
  "uid": "87a6b7e4-9fbe-5031-b764-d570d55725fb"
}