Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis

Background Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). Methods Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Delta-PPFE) was calculated.Delta-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Delta-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. Results Delta-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). Interpretation Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.This research was funded in whole or in part by the Wellcome Trust (209553/Z/17/Z). This project, J. Jacob, E. Gudmundsson, E. Denneny, J. Porter and S.M. Janes were also supported by the NIHR UCLH Biomedical Research Centre, UK. M.G. Jones, T. Wallis and C.J. Brereton acknowledge the support of the NIHR Southampton Biomedical Research Centre. Funding information for this article has been deposited with the Crossref Funder Registry.Wellcome Trust [209553/Z/17/Z]; NIHR UCLH Biomedical Research Centre, UK; NIHR Southampton Biomedical Research Centr