Mortality surrogates in combined pulmonary fibrosis and emphysema

Abstract

BackgroundIdiopathic 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.MethodsVisual 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.ResultsIn 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.ConclusionWhen 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.

Imaging in the diagnosis and management of fibrosing interstitial lung diseases

“…CPFE is predominantly found in males with a history of smoking and is characterised by severe dyspnoea, despite normal airflow and volume levels, coupled with a markedly reduced diffusing capacity of the lungs for carbon monoxide ( D LCO ) [ 65 ]. Indeed, a recent study suggests that in IPF patients with ≥10% emphysema on HRCT, changes in D LCO might reflect disease progression more accurately than declines in FVC [ 66 ]. On HRCT, CPFE manifests as varying degrees of centrilobular, paraseptal, or panacinar emphysema, often observed alongside a UIP pattern.…”