Association of Radiologic PPFE Change with Mortality in Lung Cancer Screening Cohorts

2026-03-10

AI Summary

This study investigates the clinical significance of progressive pleuroparenchymal fibroelastosis (PPFE) in individuals undergoing lung cancer screening. Using an automated algorithm, the annualized rate of change in PPFE volume (dPPFE) was quantified from low-dose computed tomography scans and integrated into multivariable Cox and negative binomial regression models to assess its association with all-cause mortality and adverse respiratory outcomes. Analyzing data from large-scale lung cancer screening cohorts (NLST and SUMMIT), the research demonstrates for the first time that dPPFE is an independent predictor of mortality risk (hazard ratio = 1.25–3.14), even after adjusting for potential confounders. Moreover, higher dPPFE values were significantly associated with increased respiratory-related hospitalizations, greater use of antibiotics and corticosteroids, and elevated dyspnea scores, underscoring the prognostic value of dynamic PPFE progression as a clinical warning sign.

Technology Category

• Search and Optimization: Distributed Search
• Computer Vision: 3D Computer Vision
• Data Mining & Knowledge Management: Intelligent Query Processing

Application Category

• Responsible Web: Human-perceived consequences of algorithmic deployment on the web
• User Modeling, Personalization and Recommendation: Studies of user behavior, including longitudinal effects of personalized systems
• Graph Algorithms and Modeling for the Web: Efficient manipulation of static and dynamic Web-related graphs

Abstract

Background: Pleuroparenchymal fibroelastosis (PPFE) is an upper lobe predominant fibrotic lung abnormality associated with increased mortality in established interstitial lung disease. However, the clinical significance of radiologic PPFE progression in lung cancer screening populations remains unclear. We investigated whether longitudinal change in PPFE quantified on low dose CT independently associates with mortality and respiratory morbidity. Methods: We analysed longitudinal low-dose CT scans and clinical data from two lung cancer screening studies: the National Lung Screening Trial (NLST; n=7980) and the SUMMIT study (n=8561). An automated algorithm quantified PPFE volume on baseline and follow up scans. Annualised change in PPFE (dPPFE) was derived and dichotomised using a distribution based threshold to define progressive PPFE. Associations between dPPFE and mortality were evaluated using Cox proportional hazards models adjusted for demographic and clinical variables. In the SUMMIT cohort, dPPFE was also examined in relation to clinical outcomes. Findings: dPPFE independently associated with mortality in both cohorts (NLST: HR 1.25, 95% CI 1.01-1.56, p=0.042; SUMMIT: HR 3.14, 95% CI 1.66-5.97, p<0.001). Kaplan-Meier curves showed reduced survival among participants with progressive PPFE in both cohorts. In SUMMIT, dPPFE was associated with higher respiratory admissions (IRR 2.79, p<0.001), increased antibiotic and steroid use (IRR 1.55, p=0.010), and a trend towards higher mMRC scores (OR 1.40, p=0.055). Interpretation: Radiologic PPFE progression independently associates with mortality across two large lung cancer screening cohorts and with adverse clinical outcomes. Quantitative assessment of PPFE progression may provide a clinically relevant imaging biomarker for identifying individuals at increased respiratory risk within screening programmes.

Problem

• PPFE
• lung cancer screening
• mortality
• radiologic progression
• respiratory morbidity

Innovation

• automated PPFE quantification
• longitudinal imaging biomarker
• low-dose CT
• radiologic progression
• interstitial lung abnormality