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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: JJ reports fees from Boehringer Ingelheim, Roche, NHSX, Takeda and GlaxoSmithKline unrelated to the submitted work. JJ was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z and the NIHR Biomedical Research Centre at University College London.
Conflict of interest: NM reports grant TUBITAK (EJP Rare Disease project “COCOS-IPF”), fees from Boehringer, Ingelheim, Roche, and Nobel Turkey unrelated to the submitted work. NM received support for travel to ATS 2020 and ATS 2021 from Roche, and to ERS 2020 from Actelion.
Conflict of interest: TJC reports unrestricted educational grants from Boehringer Ingelheim, Roche, Biogen, and Galapagos. TJC reports fees from Roche, BMS, Boehringer Ingelheim, Vicore, DevPro. TJC received assistance for travel to meetings from Boehringer Ingelheim. TJC reports participation on a Data Safety Monitoring Board or Advisory Board of Roche, BMS, Boehringer Ingelheim, Vicore, Ad Alta, Bridge Biotherapeutics, DevPro.
Conflict of interest: PV reports financial interests from Blackford Analysis.
Conflict of interest: TG is supported by Research Foundation–Flanders (FWO)-1S73921N.
Conflict of interest: LJDS is supported by Marie Sklodowska-Curie actions postdoctoral fellowship within the European Union's Horizon Europe research and innovation programme.
Conflict of interest: HJ reports fees from Boehringer ingelheim and Roche. HJ received assistance for travel to meetings from Boehringer ingelheim and Roche.
Conflict of interest: SV reports consultancy fees from Boehringer-Ingelheim and Sanofi.
Conflict of interest: MV is supported by FWO (Research Flanders Foundation) Fellowship.
Conflict of interest: SMJ reports fees from Astra-Zeneca, Bard1 Bioscience, Achilles Therapeutics, and Jansen unrelated to the submitted work. SMJ received assistance for travel to meetings from Astra Zeneca to American Thoracic Conference 2018 and from Takeda to World Conference Lung Cancer 2019 and is the Investigator Lead on grants from GRAIL Inc, GlaxoSmithKline plc and Owlstone.
Conflict of interest: AUW reports personal fees and non-financial support from Boehriger Ingelheim, Bayer and Roche Pharmaceuticals; and personal fees from Blade, outside of the submitted work.
Conflict of interest: AZ, EG, CvM, CR, RC, TJMW, ED, RS, AA, CJB, HWvE, ADL, MD, KP, FvB, JB, GC, AP, MV, PH, YM, AT, MT, LT, AN, IS, ALY, DB, DCA, JCP, MGJ, WAW report no relevant conflicts of interest.
- Received January 19, 2023.
- Accepted September 24, 2023.
- Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org
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