• David Zhang, Christina M Eckhardt, Claire McGroder, Shannon Benesh, Julie Porcelli, Christopher Depender, Kelsie Bogyo, Joseph Westrich, Amanda Thomas-Wilson, Vaidehi Jobanputra, and Christine K Garcia.
• Department of Medicine, Columbia University Irving Medical Center, New York, NY. Electronic address: dz2409@cumc.columbia.edu.
• Chest. 2024 Nov 1; 166 (5): 107110811071-1081.

BackgroundShortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown.Research QuestionWhat is the clinical impact of TL testing on the management of ILD?Study Design And MethodsPatients 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.ResultsA 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.InterpretationIncorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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