Mortality surrogates in combined pulmonary fibrosis and emphysema. (2024)

Affiliation

• Zhao A; Satsuma Lab, Centre for Medical Image Computing, UCL, London, UK.
• Gudmundsson E; Centre for Medical Image Computing, UCL, London, UK.
• Mogulkoc N; Satsuma Lab, Centre for Medical Image Computing, UCL, London, UK.
• van Moorsel C; Centre for Medical Image Computing, UCL, London, UK.
• Corte TJ; Department of Respiratory Medicine, Ege University Hospital, Izmir, Turkey.
• Vasudev P; Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
• Romei C; Department of Respiratory Medicine, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
• Chapman R; Satsuma Lab, Centre for Medical Image Computing, UCL, London, UK.
• Wallis TJM; Centre for Medical Image Computing, UCL, London, UK.
• Denneny E; Department of Radiology, Pisa University Hospital, Pisa, Italy.
• Goos T; Interstitial Lung Disease Service, Department of Respiratory Medicine, University College London Hospitals NHS Foundation Trust, London, UK.
• Savas R; NIHR Southampton Biomedical Research Centre and Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
• Ahmed A; Interstitial Lung Disease Service, Department of Respiratory Medicine, University College London Hospitals NHS Foundation Trust, London, UK.
• Brereton CJ; BREATHE, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
• van Es HW; Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
• Jo H; Department of Radiology, Ege University Hospital, Izmir, Turkey.
• De Liperi A; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
• Duncan M; NIHR Southampton Biomedical Research Centre and Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
• Pontoppidan K; Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
• De Sadeleer LJ; Department of Respiratory Medicine, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
• van Beek F; Department of Radiology, Pisa University Hospital, Pisa, Italy.
• Barnett J; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
• Cross G; NIHR Southampton Biomedical Research Centre and Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
• Procter A; Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
• Veltkamp M; Institute of Lung Health and Immunity (LHI)/Comprehensive Pneumology Center (CPC), Helmholtz Zentrum München, Munich, Germany.
• Hopkins P; Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
• Moodley Y; Department of Radiology, Royal Free London NHS Foundation Trust, London, UK.
• Taliani A; Department of Radiology, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK.
• Taylor M; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
• Verleden S; Interstitial Lung Diseases Center of Excellence, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
• Tavanti L; Division of Heart and Lungs, University Medical Center, Utrecht, The Netherlands.
• Vermant M; Queensland Centre for Pulmonary Transplantation and Vascular Disease, The Prince Charles Hospital, Chermside, Australia.
• Nair A; School of Medicine and Pharmacology, University Western Australia, Perth, Australia.
• Stewart I; Fiona Stanley Hospital, Perth, Australia.
• Janes SM; Department of Radiology, Pisa University Hospital, Pisa, Italy.
• Young AL; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
• Barber D; Antwerp Surgical Training, Anatomy and Research Centre (ASTARC), Faculty of Medicine and Health Sciences, University of Antwerp, Edegem, Belgium.
• Alexander DC; Cardiovascular and Thoracic Department, Pisa University Hospital, Pisa, Italy.
• Porter JC; BREATHE, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
• Wells AU; Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
• Jones MG; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK.
• Wuyts WA; National Heart and Lung Institute, Imperial College London, London, UK.
• Jacob J; Lungs for Living Research Centre, UCL, London, UK.

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.