Shorter Telomeres Tied to UIP Pattern, Not Fibrosis Extent, in ILD

Shorter whole genome sequencing–derived telomere length (WGS-TL) was associated with a usual interstitial pneumonia (UIP) pattern on imaging, but not with the overall extent of fibrosis, in patients with interstitial lung disease (ILD), according to recent data presented at the CHEST 2026 Annual Meeting in Phoenix, Arizona.¹

The findings suggest telomere biology may preferentially influence fibrotic patterning rather than fibrotic burden alone, supporting a distinct mechanistic pathway linking telomere dysfunction to UIP-predominant ILD, the researchers wrote.¹

Building on Genetic Research Into Telomeres and IPF

This is not the first instance in which researchers have attempted to uncover potential associations between telomere length and disease risk in patients with idiopathic pulmonary fibrosis (IPF). Unlike the present study, prior research identified rare damaging variants in IPF-associated genes—including telomere maintenance genes such as TERT, TERC, and RTEL1—and computed polygenic risk scores (PRS) for IPF and telomere length.² In that analysis, the telomere length PRS was associated with IPF in both rare variant carriers and noncarriers, and risk rose as telomeres shortened. The authors described multiple disease endotypes that shared telomere shortening but differed in their genetic drivers.²

The study presented at CHEST instead used chest CT data to assess patterns of fibrosis, including visual assessment of the CT pattern and 2 machine learning–derived quantitative measures: multiple instance learning–usual interstitial pneumonia (MIL-UIP) and data-driven texture analysis (DTA) fibrosis.^1,3 MIL-UIP was measured with a continuous score ranging from 0.0 to 1.0, with higher values predictive of histologically confirmed UIP. DTA fibrosis was measured with a continuous score ranging from 0 to 100, with higher values indicating a greater extent of fibrosis.¹

Short Telomeres Tied to UIP Pattern, Not Extent of Fibrosis

The study used data from participants in the Pulmonary Fibrosis Foundation Patient Registry who had age-adjusted WGS-TL and chest CT data obtained within 1 year of enrollment. WGS-TL was analyzed as both a continuous variable and dichotomized at the 10th percentile. Associations were assessed using Fisher's exact test for categorical variables and the Wilcoxon rank-sum test for continuous variables.¹

There were 503 participants included in the analysis, 339 of whom had IPF and 164 of whom had non-IPF ILD. In total, 138 participants (27%) had age-adjusted WGS-TL below the 10th percentile.¹ These participants were younger, with a mean (SD) age of 66 (10) years compared with 68 (10) years among those above the 10th percentile (P = .04). They were also more likely to have smoked (70% vs 60%; P = .04) and have a radiologic UIP pattern (62% vs 50%; P = .02), and they had greater mean MIL-UIP scores (0.73 [0.23] vs 0.66 [0.28]; P = .001).¹ However, there was no difference in the extent of fibrosis as measured by DTA scores when comparing those above and below the 10th percentile WGS-TL.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, CHEST 2026 presenting author, in a press release.³

These findings support an association between short telomere length and the pattern of fibrosis, as identified by both expert interpretation and machine learning–derived metrics, but not overall fibrotic burden.¹ The study did not assess disease progression, so whether telomere length or MIL-UIP scores could help track how fibrosis changes over time remains an open question.

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. Presented at: CHEST 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ. doi:10.1016/j.chest.2026.07.2673

2. McCrear S. Telomere length and polygenic risk shape endotypes in idiopathic pulmonary fibrosis. AJMC^®. February 3, 2026. Accessed November 11, 2026. https://www.ajmc.com/view/telomere-length-and-polygenic-risk-shape-endotypes-in-idiopathic-pulmonary-fibrosis

3. Shorter telomere length associated with usual interstitial pneumonia pattern in pulmonary fibrosis. News release. CHEST. October 12, 2026. Accessed November 11, 2026.