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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.* ; De Sadeleer, L.J. ; 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, S.M.* ; Young, A.L.* ; Barber, D.* ; Alexander, D.C.* ; Porter, J.C.* ; Wells, A.U.* ; Jones, M.G.* ; Wuyts, W.A.* ; Jacob, J.*

Mortality surrogates in combined pulmonary fibrosis and emphysema.

Eur. Respir. J. 63:2300127 (2023)

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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.

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