PPFE-like findings identify an IPF subgroup with shortened telomeres and poor prognosis

Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with poor prognosis. Radiological pleuroparenchymal fibroelastosis (PPFE)–like findings, characterized by upper-lobe subpleural fibrosis, have been associated with worse outcome in IPF. While short leukocyte telomere length (LTL) is a recognized prognostic factor, its relationship with PPFE-like findings remains unclear. Methods We conducted a secondary analysis of an ongoing ILD cohort. IPF patients who underwent LTL measurement by quantitative PCR were classified into those with PPFE-like findings on high-resolution computed tomography (IPF/PPFE group) and those without such findings (IPF/UIP group). Clinical characteristics, pulmonary function, telomere length, and outcomes were compared. Age-adjusted LTL was evaluated using healthy controls. Prognostic factors were analyzed using Cox regression. Results Among 179 IPF patients, 29 (16%) were assigned to the IPF/PPFE group. Compared to the IPF/UIP group (n=150), the IPF/PPFE group had lower body mass index and forced vital capacity, and significantly shorter LTL (p=0.002), with more patients below the 10th percentile of healthy controls (37.9% versus 12.0%). The IPF/PPFE group showed greater respiratory functional decline and higher mortality (65.5% versus 25.3%, p<0.001). In survival analysis, both PPFE-like findings and shortened LTL predicted worse outcomes; however, only PPFE-like findings remained independently associated with mortality in multivariate analysis. Conclusions IPF patients with PPFE-like findings constitute a distinct high-risk phenotype with shorter telomeres, accelerated progression, and poor prognosis. These findings highlight the clinical importance of recognizing PPFE-like changes and telomere biology in IPF for risk stratification and emphasize the need for close monitoring and early intervention.