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European Respiratory Journal

Publication date: 2024-04-01
Volume: 63
Publisher: European Respiratory Society

Author:

Zhao, An
Gudmundsson, Eyjolfur ; Mogulkoc, Nesrin ; van Moorsel, Coline ; Corte, Tamera J ; Vasudev, Pardeep ; Romei, Chiara ; Chapman, Robert ; Wallis, Tim JM ; Denneny, Emma ; Goos, Tinne ; Savas, Recep ; Ahmed, Asia ; Brereton, Christopher J ; Es, Hendrik W van ; Jo, Helen ; De Liperi, Annalisa ; Duncan, Mark ; Pontoppidan, Katarina ; Sadeleer, Laurens J De ; van Beek, Frouke ; Barnett, Joseph ; Cross, Gary ; Procter, Alex ; Veltkamp, Marcel ; Hopkins, Peter ; Moodley, Yuben ; Taliani, Alessandro ; Taylor, Magali ; Verleden, Stijn ; Tavanti, Laura ; Vermant, Marie ; Nair, Arjun ; Stewart, Iain ; Janes, Sam M ; Young, Alexandra L ; Barber, David ; Alexander, Daniel C ; Porter, Joanna C ; Wells, Athol U ; Jones, Mark G ; Wuyts, Wim A ; Jacob, Joseph

Keywords:

Science & Technology, Life Sciences & Biomedicine, Respiratory System, SURVIVAL, Humans, Pulmonary Emphysema, Lung, Fibrosis, Idiopathic Pulmonary Fibrosis, Emphysema, Disease Progression, Retrospective Studies, 1SE4322N|1SE4324N#56498000, 11 Medical and Health Sciences, 3201 Cardiovascular medicine and haematology

Abstract:

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (D LCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.