Abstract Rationale Telomere shortening is a proposed biomarker of accelerated lung aging and adverse outcomes across ILD subtypes 1,2. We synthesized the association between telomere length (TL) and outcomes in ILD. Methods We conducted a comprehensive search of MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and ICTRP from inception through April 4, 2025. We included adults aged 18 years and older with ILD defined by ATS/ERS criteria with leukocyte or tissue TL measurement (primarily qPCR) and time-to-event outcomes 3. Two reviewers independently screened articles, extracted data, and assessed risk of bias with QUIPS. The primary outcome was overall survival (OS). The secondary outcomes were transplant-free survival (TFS) and forced vital capacity (FVC) change (mL/year). Hazard ratios (HRs) were reported. TL was analyzed as short versus reference (short TL typically 10th percentile). Random-effects models were used in analysis, and heterogeneity was quantified with I². HRs were reconstructed from Kaplan-Meier curves using Tierney methods when needed. Results reported as % predicted per year were standardized to mL/year, assuming predicted FVC of 3.0 L (1% predicted = 30 mL). Subgroup and sensitivity analyses were performed. Methods adhered to PRISMA guidance and were prospectively registered. Protocol: OSF (DOI: 10.17605/OSF.IO/FDR48). Results We included 17 studies comprising 6290 patients (OS: N = 2593, TFS: N = 3177, FVC change: N = 2494). The meta-analysis showed that shorter TL was associated with higher mortality (OS: pooled HR 2.51; 95% CI, 1.62-3.89; P 0.001; I²=70 %), worse TFS (HR 2.72; 95% CI, 1.98-3.74; P 0.001; I²= 72%), and more rapid FVC decline (difference −67.36 mL/year; 95% CI, −111.47 to − 63.25; P 0.001; I²= 33%). Conclusions Shorter TL is consistently associated with worse survival and accelerated physiological decline across IPF and non-IPF ILD. Between-study heterogeneity likely reflects differences in ILD subtype mix, transplant status, TL assays, and threshold definitions. These findings support incorporating TL into risk stratification to refine prognostication, enrich clinical trial cohorts, and inform management pathways. Alongside imaging and functional indices, TL represents a promising molecular biomarker to guide individualized ILD care. This abstract is funded by: None
Goto et al. (2026) studied this question.