Pleuroparenchymal fibroelastosis in idiopathic pulmonary fibrosis: Survival analysis using visual and computer-based computed tomography assessment

Background: Idiopathic pulmonary fibrosis (IPF) and pleuroparenchymal fibroelastosis (PPFE) are known to have poor outcomes but detailed examinations of prognostic significance of an association between these morphologic processes are lacking. Methods: Retrospective observational study of independent derivation and validation cohorts of IPF populations. Upper-lobe PPFE extent was scored visually (vPPFE) as categories of absent, moderate, marked. Computerised upper-zone PPFE extent (cPPFE) was examined continuously and using a threshold of 2.5% pleural surface area. vPPFE and cPPFE were evaluated against 1-year FVC decline (estimated using mixed-effects models) and mortality. Multivariable models were adjusted for age, gender, smoking history, antifibrotic treatment and diffusion capacity for carbon monoxide. Findings: PPFE prevalence was 49% (derivation cohort, n = 142) and 72% (validation cohort, n = 145). vPPFE marginally contributed 3-14% to variance in interstitial lung disease (ILD) severity across both cohorts. In multivariable models, marked vPPFE was independently associated with 1-year FVC decline (derivation: regression coefficient 18.3, 95 CI 8.47-28.2%; validation: 7.51, 1.85-13.2%) and mortality (derivation: hazard ratio [HR] 7.70, 95% CI 3.50-16.9; validation: HR 3.01, 1.33-6.81). Similarly, continuous and dichotomised cPPFE were associated with 1-year FVC decline and mortality (cPPFE > 2.5% derivation: HR 5.26, 3.00-9.22; validation: HR 2.06, 1.28-3.31). Individuals with cPPFE > 2.5% or marked vPPFE had the lowest median survival, the cPPFE threshold demonstrated greater discrimination of poor outcomes at two and three years than marked vPPFE. Interpretation: PPFE quantification supports distinction of IPF patients with a worse outcome independent of established ILD severity measures. This has the potential to improve prognostic management and elucidate separate pathways of disease progression. Funding: This research was funded in whole or in part by the Wellcome Trust [209,553/Z/17/Z] and the NIHR UCLH Biomedical Research Centre, UK. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)