The following is a summary of “Clinical Impact of Telomere Length Testing for Interstitial Lung Disease,” published in the June 2024 issue of Pulmonology by Zhang et al.

Shortened telomere length (TL) has been identified as a significant genomic risk factor for fibrotic interstitial lung disease (ILD), yet its application in clinical management remains unclear. This study aims to elucidate the clinical impact of TL testing on managing ILD. This research at the Columbia University ILD clinic involved patients undergoing CLIA-certified TL testing using flow cytometry and fluorescence in-situ hybridization (FlowFISH) as part of their clinical evaluation. 

Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH, and patients identified with short TL or with a family history of ILD were offered genetic counseling and testing. The study included 108 patients, with 50% having familial pulmonary fibrosis and 25% exhibiting extrapulmonary manifestations, either in themselves or a relative (41%). The prevalence of short TL was found to be 46%, consistent across various ILD diagnoses. Clinical features indicative of short telomere syndrome were significantly associated with short TL detection (OR 2.00, 95% CI [1.27, 3.32]). TL testing influenced clinical management decisions for 35 (32%) patients, predominantly leading to reducing or avoiding immunosuppressive treatments. Among the 34 patients who underwent genetic testing, 10 (29%) were found to have positive or candidate diagnostic findings in telomere-related genes. 

Notably, TL testing below the 1st percentile facilitated the reclassification of 8 out of 9 variants of uncertain significance (VUS) into actionable findings. Although the qPCR assay correlated with FlowFISH results, the age-adjusted percentile cutoffs between the two methods were not equivalent. These findings suggest that TL testing can significantly influence clinical management decisions in patients with ILD, particularly by identifying individuals who may benefit from adjusted therapeutic strategies, thereby emphasizing the potential for TL testing to enhance personalized treatment approaches in ILD management.

Source: sciencedirect.com/science/article/abs/pii/S0012369224008080