eprintid: 10138274
rev_number: 32
eprint_status: archive
userid: 608
dir: disk0/10/13/82/74
datestamp: 2021-11-12 17:00:29
lastmod: 2022-08-17 15:03:03
status_changed: 2021-11-12 17:11:40
type: article
succeeds: 10130339
metadata_visibility: show
creators_name: Jacob, J
title: Pleuroparenchymal Fibroelastosis in Idiopathic Pulmonary Fibrosis: Survival Analysis using Visual and Computer-Based Computed Tomography Assessment
ispublished: pub
subjects: UCH
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: K71
divisions: B04
divisions: C05
divisions: F48
keywords: Pleuroparenchymal fibroelastosis, PPFE, Idiopathic pulmonary fibrosis, IPF, Computed tomography, Quantitative analysis
note: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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.
date: 2021-08
date_type: published
official_url: https://doi.org/10.1016/j.eclinm.2021.101009
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1873148
doi: 10.1016/j.eclinm.2021.101009
lyricists_name: Alexander, Daniel
lyricists_name: Gudmundsson, Eyjolfur
lyricists_name: Jacob, Joseph
lyricists_name: Janes, Samuel
lyricists_id: DALEX06
lyricists_id: EGUDM72
lyricists_id: JJACO76
lyricists_id: SMJAN15
actors_name: Jacob, Joseph
actors_id: JJACO76
actors_role: owner
full_text_status: public
publication: EClinicalMedicine
volume: 38
article_number: 101009
citation:        Jacob, J;      (2021)    Pleuroparenchymal Fibroelastosis in Idiopathic Pulmonary Fibrosis: Survival Analysis using Visual and Computer-Based Computed Tomography Assessment.                   EClinicalMedicine , 38     , Article 101009.  10.1016/j.eclinm.2021.101009 <https://doi.org/10.1016/j.eclinm.2021.101009>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10138274/1/Jacob_1-s2.0-S2589537021002893-main.pdf