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

Eyjolfur Gudmundsson; An Zhao; Nesrin Mogulkoc; Iain Stewart; Mark G Jones; Coline H M Van Moorsel; Recep Savas; Christopher J Brereton; Hendrik W Van Es; Omer Unat; Katarina Pontoppidan; Frouke Van Beek; Marcel Veltkamp; Bahareh Gholipour; Arjun Nair; Athol U Wells; Sam M Janes; Daniel C Alexander; Joseph Jacob

doi:10.1016/j.eclinm.2021.101009

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

EClinicalMedicine. 2021 Jul 13:38:101009. doi: 10.1016/j.eclinm.2021.101009. eCollection 2021 Aug.

Authors

Eyjolfur Gudmundsson¹, An Zhao¹, Nesrin Mogulkoc², Iain Stewart³, Mark G Jones⁴, Coline H M Van Moorsel⁵, Recep Savas⁶, Christopher J Brereton⁴, Hendrik W Van Es⁷, Omer Unat², Katarina Pontoppidan⁴, Frouke Van Beek⁵, Marcel Veltkamp^{5

8}, Bahareh Gholipour⁹, Arjun Nair⁹, Athol U Wells¹⁰, Sam M Janes¹¹, Daniel C Alexander¹, Joseph Jacob^{1

11}

Affiliations

¹ Centre for Medical Image Computing, UCL, 1st Floor, 90 High Holborn, London WC1V6LJ, United Kingdom.
² Department of Respiratory Medicine, Ege University Hospital, Izmir, Turkey.
³ National Heart & Lung Institute, Imperial College London, London, United Kingdom.
⁴ NIHR Southampton Biomedical Research Centre and Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom.
⁵ Department of Pulmonology, Interstitial Lung Diseases Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands.
⁶ Department of Radiology, Ege University Hospital, Izmir, Turkey.
⁷ Department of Radiology, St Antonius Hospital, Nieuwegein, the Netherlands.
⁸ Division of Heart and Lungs, University Medical Center, Utrecht, the Netherlands.
⁹ Department of Radiology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
¹⁰ Interstitial Lung Disease Unit, Royal Brompton Hospital, Imperial College, London, United Kingdom.
¹¹ Lungs for Living Research Centre, UCL, London, United Kingdom.

Abstract

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.

Keywords: Computed tomography; IPF; PPFE, Idiopathic pulmonary fibrosis; Pleuroparenchymal fibroelastosis; Quantitative analysis.