Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis

Background: computer quantification of baseline computed tomography (CT) radiologic 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 radiologic PPFE-like lesions (∆-PPFE) was calculated. ∆-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated ∆-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, gender, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change.Findings: ∆-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 (HR=1.25, 95% CI 1.16–1.34, p<0.0001) and the FHP cohort (HR=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 correlate strongly with measures of fibrosis progression.