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Zhao, An; Gudmundsson, Eyjolfur; Mogulkoc, Nesrin; van Moorsel, Coline; Corte, Tamera J; Vasudev, Pardeep; Romei, Chiara; Chapman, Robert; Wallis, Tim J M; Denneny, Emma; Goos, Tinne; Savas, Recep; Ahmed, Asia; Brereton, Christopher J; van Es, Hendrik W; Jo, Helen; De Liperi, Annalisa; Duncan, Mark; Pontoppidan, Katarina; De Sadeleer, Laurens J; 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
The European respiratory journal, 04/2024, Volume: 63, Issue: 4Journal Article
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. 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 ( ) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year 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. When assessing disease progression in IPF, decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.
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