Role of genetic testing in pleuroparenchymal fibroelastosis

<bold>Introduction:</bold> There is increasing recognition of the importance of genetic testing in the evaluation of pulmonary fibrosis, particularly since telomere biology disorders (TBD) and surfactant protein gene abnormalities are clinically indistinguishable from cases without known pathogenic gene variants. In this study, we aim to demonstrate the role of genetic testing in pleuroparenchymal fibroelastosis (PPFE) through analysis of 6 cases of PPFE. <bold>Methods:</bold> 70 patients with premature or familial pulmonary fibrosis were evaluted for PPFE through radiologic and/or histopathologic methods. Flow-FISH testing of peripheral blood analyzed telomere length and an exome-based panel assessed 33 pertinent genes using DNA from whole blood. <bold>Results:</bold> Among the 70 patients, six patients (8.6%) with PPFE were identified. Five patients were female and median age was 61 years (range 32-70). All PPFE patients had telomere or surfactant protein variants. Five patients (83%) had lymphocyte and granulocyte telomere length less than the 10th percentile. Of these five, four (80%) had a genetic variant in known telomere-related genes. One patient had a heterozygous surfactant protein A2 (SFTPA2) variant. Further data are provided in Table 1. <fig><object-id>erj;64/suppl_68/PA4292/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Conclusions:</bold> Evaluating for TBD and surfactant protein gene variants in patients with PPFE can improve understanding of the underlying disease process and contribute to improved diagnosis and management of patients and their relatives.