Mortality surrogates in combined pulmonary fibrosis and emphysema

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

doi:10.1183/13993003.00127-2023

Mortality surrogates in combined pulmonary fibrosis and emphysema

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

^*Corresponding author for this work

Department of Pulmonary Diseases

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	2300127
Journal	The European respiratory journal
Volume	63
Issue number	4
DOIs	https://doi.org/10.1183/13993003.00127-2023
Publication status	Published - Apr 2024

Keywords

Disease Progression
Emphysema/complications
Fibrosis
Humans
Idiopathic Pulmonary Fibrosis
Lung
Pulmonary Emphysema/complications
Retrospective Studies

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10.1183/13993003.00127-2023

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Zhao, A., Gudmundsson, E., Mogulkoc, N., van Moorsel, C., Corte, T. J., Vasudev, P., Romei, C., Chapman, R., Wallis, T. J. M., Denneny, E., Goos, T., Savas, R., Ahmed, A., Brereton, C. J., van Es, H. W., Jo, H., De Liperi, A., Duncan, M., Pontoppidan, K., ... Jacob, J. (2024). Mortality surrogates in combined pulmonary fibrosis and emphysema. The European respiratory journal, 63(4), Article 2300127. https://doi.org/10.1183/13993003.00127-2023

@article{a8e7099e8db147529125bad84f6e0501,

title = "Mortality surrogates in combined pulmonary fibrosis and emphysema",

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 (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.",

keywords = "Disease Progression, Emphysema/complications, Fibrosis, Humans, Idiopathic Pulmonary Fibrosis, Lung, Pulmonary Emphysema/complications, Retrospective Studies",

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

year = "2024",

month = apr,

doi = "10.1183/13993003.00127-2023",

language = "English",

volume = "63",

journal = "The European respiratory journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "4",

}

Zhao, A, Gudmundsson, E, Mogulkoc, N, van Moorsel, C, Corte, TJ, Vasudev, P, Romei, C, Chapman, R, Wallis, TJM, Denneny, E, Goos, T, Savas, R, Ahmed, A, Brereton, CJ, van Es, HW, Jo, H, De Liperi, A, Duncan, M, Pontoppidan, K, De Sadeleer, LJ, van Beek, F, Barnett, J, Cross, G, Procter, A, Veltkamp, M, Hopkins, P, Moodley, Y, Taliani, A, Taylor, M, Verleden, S, Tavanti, L, Vermant, M, Nair, A, Stewart, I, Janes, SM, Young, AL, Barber, D, Alexander, DC, Porter, JC, Wells, AU, Jones, MG, Wuyts, WA & Jacob, J 2024, 'Mortality surrogates in combined pulmonary fibrosis and emphysema', The European respiratory journal, vol. 63, no. 4, 2300127. https://doi.org/10.1183/13993003.00127-2023

TY - JOUR

T1 - Mortality surrogates in combined pulmonary fibrosis and emphysema

AU - Zhao, An

AU - Gudmundsson, Eyjolfur

AU - Mogulkoc, Nesrin

AU - van Moorsel, Coline

AU - Corte, Tamera J

AU - Vasudev, Pardeep

AU - Romei, Chiara

AU - Chapman, Robert

AU - Wallis, Tim J M

AU - Denneny, Emma

AU - Goos, Tinne

AU - Savas, Recep

AU - Ahmed, Asia

AU - Brereton, Christopher J

AU - van Es, Hendrik W

AU - Jo, Helen

AU - De Liperi, Annalisa

AU - Duncan, Mark

AU - Pontoppidan, Katarina

AU - De Sadeleer, Laurens J

AU - van Beek, Frouke

AU - Barnett, Joseph

AU - Cross, Gary

AU - Procter, Alex

AU - Veltkamp, Marcel

AU - Hopkins, Peter

AU - Moodley, Yuben

AU - Taliani, Alessandro

AU - Taylor, Magali

AU - Verleden, Stijn

AU - Tavanti, Laura

AU - Vermant, Marie

AU - Nair, Arjun

AU - Stewart, Iain

AU - Janes, Sam M

AU - Young, Alexandra L

AU - Barber, David

AU - Alexander, Daniel C

AU - Porter, Joanna C

AU - Wells, Athol U

AU - Jones, Mark G

AU - Wuyts, Wim A

AU - Jacob, Joseph

PY - 2024/4

Y1 - 2024/4

N2 - 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 (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.

AB - 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 (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.

KW - Disease Progression

KW - Emphysema/complications

KW - Fibrosis

KW - Humans

KW - Idiopathic Pulmonary Fibrosis

KW - Lung

KW - Pulmonary Emphysema/complications

KW - Retrospective Studies

U2 - 10.1183/13993003.00127-2023

DO - 10.1183/13993003.00127-2023

M3 - Article

C2 - 37973176

SN - 0903-1936

VL - 63

JO - The European respiratory journal

JF - The European respiratory journal

IS - 4

M1 - 2300127

ER -

Mortality surrogates in combined pulmonary fibrosis and emphysema

Abstract

Keywords

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