Mortality surrogates in combined pulmonary fibrosis and emphysema.
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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
Аннотация
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.