Short Telomeres Linked to UIP Pattern, Not Fibrosis Extent, in ILD

Shorter age-adjusted telomere length was associated with a usual interstitial pneumonia (UIP) radiologic pattern but not with overall extent of fibrosis in patients with interstitial lung disease (ILD), according to a registry analysis presented at the American College of Chest Physicians (CHEST) 2026 Annual Meeting, held October 18 to 21 in Phoenix, Arizona.^1,2

The association held for both expert visual CT interpretation and a machine learning–derived UIP score, according to the investigators.¹ They suggested telomere biology may preferentially influence fibrotic patterning rather than fibrotic burden, pointing to a distinct mechanistic pathway linking telomere dysfunction to UIP-predominant ILD.¹

"MIL-UIP may help identify patients with telomere shortening, supporting a role for imaging-derived biomarkers in recognizing biologically distinct ILD phenotypes," said Samuel B. Konkol, MD, presenting author.²

Telomere length and UIP pattern in the Pulmonary Fibrosis Foundation Patient Registry

The analysis included Pulmonary Fibrosis Foundation Patient Registry participants with age-adjusted whole-genome sequencing–derived telomere length (WGS-TL) and chest CT obtained within 1 year of enrollment.¹ Of 503 participants, 339 had idiopathic pulmonary fibrosis (IPF) and 164 had non-IPF ILD, and 138 (27%) had WGS-TL below the 10th percentile.¹

Radiologic measures included visual CT pattern and 2 machine learning–derived scores.¹ Multiple instance learning–UIP (MIL-UIP) ranges from 0.0 to 1.0, with higher values predictive of histologically confirmed UIP, and data-driven texture analysis (DTA) fibrosis ranges from 0 to 100, with higher values indicating greater extent of fibrosis.¹

Participants with WGS-TL below the 10th percentile were more likely to have a radiologic UIP pattern (62% vs 50%; P = .02) and had higher MIL-UIP scores (mean, 0.73 [standard deviation (SD), 0.23] vs 0.66 [SD, 0.28]; P = .001).¹ DTA fibrosis scores did not differ between groups.¹

Unadjusted comparisons and limitations of the telomere analysis

Participants with short telomeres were younger (mean, 66 [SD, 10] vs 68 [SD, 10] years; P = .04) and more likely to have smoked (70% vs 60%; P = .04).¹ Group comparisons used Fisher exact and Wilcoxon rank sum tests, and the abstract did not report adjustment for age, smoking, or ILD diagnosis.¹

The abstract also did not report results from the continuous WGS-TL analysis, DTA fibrosis values, or separate findings for IPF and non-IPF ILD.¹ Because IPF accounted for 67% of participants and is defined in part by a UIP pattern, the distribution of diagnoses across telomere groups may influence the observed association.

The cross-sectional design does not establish whether telomere shortening drives the UIP pattern, and MIL-UIP has not been validated as a screening tool for telomere shortening.

The investigators concluded shorter age-adjusted WGS-TL is associated with a UIP pattern by both expert and machine learning–derived assessment, but not with the overall extent of fibrosis.¹

References

1. Konkol SB, Receveur B, Ma SF, et al. Shorter telomere length associates with automated detection of usual interstitial pneumonia on imaging in pulmonary fibrosis. CHEST. 2026;170(4S). doi:10.1016/j.chest.2026.07.2673

2. American College of Chest Physicians. Shorter telomere length associated with usual interstitial pneumonia pattern in pulmonary fibrosis. News release. October 12, 2026. Accessed October 19, 2026.