Evaluation of a screening protocol for telomere biology disorders in individuals with interstitial lung disease undergoing lung transplant evaluation.

Background: Because of the potential for extrapulmonary disease, it is important for lung transplant programmes to identify telomere biology disorder (TBD)-related interstitial lung disease (ILD). The aim of this study was to evaluate a TBD phenotype screen among ILD patients undergoing lung transplant evaluation, including the sensitivity and specificity of individual phenotype screening questions and the characteristics of patients with TBD identified outside of the screening protocol. Methods: This was a retrospective cohort study of adults with ILD who underwent lung transplant evaluation from 1 January 2018 to 28 February 2023. The TBD phenotype screen included early greying, family history of ILD and unexplained liver disease, cytopenias or macrocytosis. TBD screen-positive patients underwent telomere length (TL) testing. Results: Among 383 patients evaluated, 92 (24.0%) had a positive phenotype screen. 58 (63.0%) had early greying, 39 (42.4%) had a first-degree relative with ILD and 29 (31.5%) had unexplained macrocytosis or cytopenias. Using granulocyte and lymphocyte TL <10th percentile, 51 (55.4%) patients met criteria for a TBD. Early greying had the highest sensitivity for TBD (72.5%) with specificity increasing with the number of positive screening questions. Among the 23 patients who underwent TL testing outside of the screening protocol, most commonly because of an early age of onset of ILD, eight (34.8%) had TL between the 1st and 10th percentile. Conclusions: Lymphocyte and granulocyte TL <10th is common among TBD phenotype screen-positive ILD patients undergoing transplant evaluation. Inclusion of additional screening questions related to age of onset of ILD could improve the sensitivity of the protocol for short TL.