Implementation of a prospective screening strategy to identify adults with a telomere biology disorder among those undergoing lung transplant evaluation for interstitial lung disease.

Autor: Banaszak LG; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA. Electronic address: lbanaszak@uwhealth.org., Smith-Simmer K; Oncology Genetics, University of Wisconsin Carbone Cancer Center, UW Health, Madison, WI, 53705, USA., Shoger K; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA., Lovrien L; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA., Malik A; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA., Sandbo N; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA., Sultan S; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA., Guzy R; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA., Lowery EM; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA., Churpek JE; Department of Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA. Electronic address: jchurpek@wisc.edu.
Jazyk: angličtina
Zdroj: Respiratory medicine [Respir Med] 2023 Dec; Vol. 220, pp. 107464. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1016/j.rmed.2023.107464
Abstrakt: Introduction: Patients with interstitial lung disease (ILD) secondary to telomere biology disorders (TBD) experience increased morbidity after lung transplantation. Identifying patients with TBD may allow for personalized management to facilitate better outcomes. However, establishing a TBD diagnosis in adults is challenging.
Methods: A TBD screening questionnaire was introduced prospectively into the lung transplant evaluation. Patients with ILD screening positive were referred for comprehensive TBD phenotyping and concurrent telomere length measurement and germline genetic testing.
Results: Of 98 patients, 32 (33%) screened positive. Eight patients (8% of total; 25% of patients with a positive screen) met strict TBD diagnostic criteria, requiring either critically short lymphocyte telomeres (<1st percentile) (n = 4), a pathogenic variant in a TBD-associated gene (n = 1), or both (n = 3) along with a TBD clinical phenotype. Additional patients not meeting strict diagnostic criteria had histories consistent with TBD along with telomere lengths <10th percentile and/or rare variants in TBD-associated genes, highlighting a critical need to refine TBD diagnostic criteria for this patient population.
Conclusion: A TBD phenotype screening questionnaire in patients with ILD undergoing lung transplant evaluation has a diagnostic yield of 25%. Additional gene discovery, rare variant functional testing, and refined TBD diagnostic criteria are needed to realize the maximum benefit of testing for TBD in patients undergoing lung transplantation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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