Clinical Impact of Telomere Length Testing for Interstitial Lung Disease.

IF 9.5 1区医学 Q1 CRITICAL CARE MEDICINE Chest Pub Date : 2024-11-01 Epub Date: 2024-06-29 DOI:10.1016/j.chest.2024.06.006

David Zhang, Christina M Eckhardt, Claire McGroder, Shannon Benesh, Julie Porcelli, Christopher Depender, Kelsie Bogyo, Joseph Westrich, Amanda Thomas-Wilson, Vaidehi Jobanputra, Christine K Garcia

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Abstract

Background: Shortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown.

Research question: What is the clinical impact of TL testing on the management of ILD?

Study design and methods: Patients were evaluated in the Columbia University ILD clinic and underwent Clinical Laboratory Improvement Amendments-certified TL testing by flow cytometry and fluorescence in situ hybridization (FlowFISH) as part of clinical treatment. Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared with research quantitative polymerase chain reaction (qPCR) TL measurement.

Results: A total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR, 2.00; 95% CI, 1.27-3.32). TL testing led to clinical treatment changes for 35 patients (32%), most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n = 34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 patients (29%). Inclusion of TL testing below the 1st percentile helped reclassify eight of nine variants of uncertain significance into actionable findings. The quantitative polymerase chain reaction test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays.

Interpretation: Incorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.

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端粒长度检测对间质性肺病的临床影响

背景：端粒长度（TL）缩短是纤维化间质性肺病（ILD）的一个基因组风险因素，但其在临床管理中的作用尚不清楚：研究设计和方法：哥伦比亚大学 ILD 诊所对患者进行了评估，并通过流式细胞术和荧光原位杂交（FlowFISH）对患者进行了 CLIA 认证的 TL 检测，作为临床治疗的一部分。流式荧光原位杂交法将粒细胞或淋巴细胞的短TL定义为低于第10个年龄调整百分位数。如果患者有短TL或ILD家族史，则为其提供遗传咨询和检测。将 FlowFISH TL 与 qPCR TL 测量结果进行比较：共有 108 名患者接受了 TL 检测，其中包括具有短端粒综合征临床特征的患者，如家族性肺纤维化（50%）或患者本人（25%）或亲属（41%）的肺外表现。短端粒综合征的总发病率为 46%，在不同临床 ILD 诊断中的发病率相似。短端粒临床特征的数量与检测出短端粒相关（OR 2.00，95% CI [1.27，3.32]）。端粒检测导致 35 例（32%）患者的临床管理发生了变化，最常见的变化是减少或避免使用免疫抑制剂。在接受基因检测的患者（34 人）中，有 10 人（29%）的端粒相关基因检测结果为阳性或候选诊断结果。纳入低于第一百分位数的端粒检测有助于将 9 个意义不确定的变异（VUS）中的 8 个重新归类为可操作的结果。qPCR 检测与 FlowFISH 检测结果相关，但两种检测方法的年龄调整百分位数截止值可能并不相同：在 ILD 中纳入 TL 检测影响了临床管理，并发现了新的可操作遗传变异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chest 医学-呼吸系统

CiteScore

13.70

自引率

3.10%

发文量

3369

审稿时长

15 days

期刊介绍： At CHEST, our mission is to revolutionize patient care through the collaboration of multidisciplinary clinicians in the fields of pulmonary, critical care, and sleep medicine. We achieve this by publishing cutting-edge clinical research that addresses current challenges and brings forth future advancements. To enhance understanding in a rapidly evolving field, CHEST also features review articles, commentaries, and facilitates discussions on emerging controversies. We place great emphasis on scientific rigor, employing a rigorous peer review process, and ensuring all accepted content is published online within two weeks.