Mortality surrogates in combined pulmonary fibrosis and emphysema
Mortality surrogates in combined pulmonary fibrosis and emphysema
Background: idiopathic pulmonary fibrosis (IPF) with co-existent 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=317:183; replication cohort=358:152), who were subgrouped using 10%, or 15% visual emphysema thresholds, and an unsupervised machine learning model considering emphysema and ILD extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (DLco) 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 DLco compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year DLco 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, DLco decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.
Zhao, An
2c02130c-b640-49d8-a48a-778167209d18
Gudmundsson, Eyjolfur
9c6805d8-0f33-4872-a99f-44f0fbf19bf7
Mogulkoc, Nesrin
433ea942-9ac8-4c78-86a3-f1d003043852
Wallis, Tim J.M.
cf385c2a-ef94-4435-8066-31acf23f6f99
Brereton, Christopher J.
948ca4ea-b04c-4b7a-bfe4-f79f184d7e43
Jones, Mark G.
a6fd492e-058e-4e84-a486-34c6035429c1
Zhao, An
2c02130c-b640-49d8-a48a-778167209d18
Gudmundsson, Eyjolfur
9c6805d8-0f33-4872-a99f-44f0fbf19bf7
Mogulkoc, Nesrin
433ea942-9ac8-4c78-86a3-f1d003043852
Wallis, Tim J.M.
cf385c2a-ef94-4435-8066-31acf23f6f99
Brereton, Christopher J.
948ca4ea-b04c-4b7a-bfe4-f79f184d7e43
Jones, Mark G.
a6fd492e-058e-4e84-a486-34c6035429c1
Zhao, An, Gudmundsson, Eyjolfur, Mogulkoc, Nesrin and Jones, Mark G.
,
et al.
(2023)
Mortality surrogates in combined pulmonary fibrosis and emphysema.
European Respiratory Journal, 62 (6).
(doi:10.1183/13993003.00127-2023).
Abstract
Background: idiopathic pulmonary fibrosis (IPF) with co-existent 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=317:183; replication cohort=358:152), who were subgrouped using 10%, or 15% visual emphysema thresholds, and an unsupervised machine learning model considering emphysema and ILD extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (DLco) 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 DLco compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year DLco 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, DLco decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.
Text
Mortality surrogates in combined pulmonary fibrosis and emphysema_ERJ
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More information
Accepted/In Press date: 24 September 2023
e-pub ahead of print date: 16 November 2023
Additional Information:
This research was funded in whole or in part by the Wellcome Trust [209553/Z/17/Z]. For the purpose of open access, the author has applied a CC-BY public copyright licence to any author accepted manuscript version arising from this submission.
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Local EPrints ID: 483374
URI: http://eprints.soton.ac.uk/id/eprint/483374
ISSN: 0903-1936
PURE UUID: e425ca5e-3dd4-4979-a757-cd7b02171b68
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Date deposited: 30 Oct 2023 12:11
Last modified: 18 Mar 2024 03:07
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Contributors
Author:
An Zhao
Author:
Eyjolfur Gudmundsson
Author:
Nesrin Mogulkoc
Author:
Tim J.M. Wallis
Author:
Christopher J. Brereton
Corporate Author: et al.
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