Extrapulmonary manifestations of a telomere syndrome in patients with idiopathic pulmonary fibrosis are associated with decreased survival

• Published in: Respirology (Carlton, Vic.) Vol. 27; no. 11; pp. 959 - 965
• Main Authors: Hoffman, Thijs W., Vis, Joanne J., Biesma, Douwe H., Grutters, Jan C., Moorsel, Coline H. M.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2022; Wiley Subscription Services, Inc
• Subjects: Dystrophy; extrapulmonary manifestations; familial pulmonary fibrosis; Family medical history; Fibrosis; Genetic analysis; Hematological diseases; Hematology; idiopathic pulmonary fibrosis; Laboratories; Leukopenia; Liver diseases; Lung diseases; Patients; Phenotypes; Pulmonary fibrosis; Respiratory diseases; telomere syndrome; Telomeres; Thrombocytopenia; idiopathic pulmonary fibrosis; extrapulmonary manifestations; telomere syndrome; familial pulmonary fibrosis
• ISSN: 1323-7799; 1440-1843
• DOI: 10.1111/resp.14264

Background and objective Idiopathic pulmonary fibrosis (IPF) is a heterogenous disease with a median survival of 3–4 years. Patients with mutations in telomere‐related genes exhibit extrapulmonary signs and symptoms. These patients represent a distinct phenotype of IPF with worse survival. As genetic analyses are not available for most patients with IPF, we sought to determine the predictive value of extrapulmonary signs and symptoms of a telomere syndrome in patients with IPF. Methods We retrospectively studied 409 patients with IPF. Clinical characteristics, laboratory results and family history suggestive of a telomere syndrome were related to leukocyte telomere length measured by quantitative PCR and patient outcomes. Results The cohort included 293 patients with sporadic IPF and 116 patients with a background of familial pulmonary fibrosis. Any or a combination of a clinical history (haematological disease, liver disease, early greying of hair, nail dystrophy, skin abnormalities), a family history or haematological laboratory abnormalities (macrocytosis, anaemia, thrombopenia or leukopenia) suggestive of a telomere syndrome was present in 27% of IPF patients and associated with shorter leukocyte telomere length and shorter survival (p = 0.002 in a multivariate model). In sporadic IPF, having either a clinical history, family history or haematological laboratory abnormalities was not significantly associated with decreased survival (p = 0.07 in a multivariate model). Conclusion Taking a careful clinical and family history focused on extrapulmonary manifestations of a telomere syndrome can provide important prognostic information in patients with IPF, as this is associated with shorter survival. Clinical features suggestive of a telomere syndrome are present in a quarter of patients with idiopathic pulmonary fibrosis. These features include a history or family history of haematological or liver disease, or haematological laboratory abnormalities. They are associated with lower leukocyte telomere length and are independently associated with decreased survival. See related Editorial