B41-07 Comparison of Clinical and Radiological Features in Patients With Pulmonary Fibrosis and Telomere Lengths

Abstract Rationale A subset of patients with pulmonary fibrosis (PF) have pathogenic variants in telomere maintenance genes (such as TERT, TERC, DKC1, TNF2, PARN) resulting in short telomeres ≤ 10th percentile (ST). ST are associated with progressive disease and decreased transplant free survival. Among a cohort of PF patients who underwent genetic testing for telomere length, we sought to determine if there are clinical and high resolution computed tomographic scans (HRCT) features that might distinguish PF patients with ST from those with normal telomere length (NT). Methods Single center retrospective observational study (IRB:STUDY00019345). We identified patients from our clinical database with PF whose lung disease had progressed to require lung transplantation (LT) and were subjected to genetic testing prior to LT. Clinical data was abstracted from the medical record. A chest radiologist (SP) and a research assistant (RR) reviewed HRCT patterns and distribution on HRCT from patients with PF pre-LT blinded to patient telomere status, age and other demographic features. HRCT pattern and clinical characteristics were documented. Fisher’s exact test, the independent samples t-test, and the Wilcoxon rank-sum test were used to calculate p-values as appropriate, given the data type and the skewness. Results (Table) Of 24 included patients, 15 had ST. Median age at diagnosis was 53 years and 75% of the cohort was male. Pre-LT, mean FVC overall was 1.98L (47.3% predicted), with mean DLCO 10.3mL/min/mmHg (37.9%) without statistically significant differences between groups. Patients with ST more often had a diagnosis of IPF per 2022 guideline criteria compared to those with NT (12/15 IPF in ST group vs 3/9 IPF in NT group, p 0.036). Six of 15 (40%) patients with ST had a pattern of combined pleuro-parenchymal fibroelastosis-usual interstitial pneumonia (PPFE-UIP) in comparison to 1 of 9 patients (12.5%) with NT (p = 0.191). More patients in the ST group had segment 4 liver hypoplasia, but this did not meet statistical significance. Conclusion Patients with PF and ST more often had an underlying diagnosis of IPF compared to those with NT. Although more patients with combined PPFE-UIP had ST, this did not reach statistical significance. Further study with a larger number of patients is warranted to determine if the HRCT image pattern of combined PPFE-UIP could be a biomarker of patients with ST. This abstract is funded by: N/a