Background: 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.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 baselineD_LCOcompared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-yearD_LCOdecline 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_LCOdecline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.

This paper presents an open-source pipeline for simulating flow and flow-related processes in (embedded) tubular structures. Addressing a gap in computational fluid dynamics (CFD) and simulation sciences, it facilitates the transition from raw three-dimensional imaging, graph networks or computer aided design (CAD) models of tubular objects to refined, simulation-ready meshes. This transition, traditionally labour-intensive, is streamlined through a series of innovative steps that include surface mesh processing, centre-line construction, anisotropic mesh generation and volumetric meshing, leading to finite element method (FEM) simulations. The pipeline leverages a range of open-source software and libraries, notably GIBBON , FEniCS and Paraview , to provide flexibility and broad applicability across different simulation scenarios, ranging from biomedical to industrial applications. We demonstrate the versatility of our approach through five applications, including the mesh generation for soil–root systems, lung airways, microcirculation networks and portal vein networks, each originating from a different data source. Moreover, for several of these cases, we incorporate CFD simulations and strategies for 3D–1D coupling between the embedding domain and the embedded structures. Finally, we outline some future perspectives aimed at enhancing accuracy, reducing computational time and incorporating advanced modelling and boundary condition strategies to further refine the framework’s capabilities.

Aim: Patients with interstitial lung disease of UIP pattern who are ANCA-positive (Anti-neutrophil cytoplasmic antibody, MPO subtype) without signs of vasculitis are not well characterised. We wished to compare this subgroup with the generality of our patients with IPF. Method: The patients were from Ege Hospital and submitted to the EMPIRE Registry, which performed the statistical analysis. We compared 23 patients with UIP who were ANCA-positive at presentation but without signs of vasculitis against 497 patients with IPF who were ANCA-negative, comparing demographics, smoking history, comorbidities, HRCT appearances, anti-fibrotics treatment and survival. Results: The ANCA-positive patients were marginally older (median 70 vs. 67 years, p = 0.03). They were less likely to be diabetic (4.8% vs. 24%, p=0.02) and much less likely to have pulmonary hypertension (0% vs 18%, p = 0.004) but more likely to have COPD (19% vs 5%, p=0.024). They were much more likely to have an HRCT pattern of definite UIP (86% vs 58%, p = 0.007). There were no significant differences in lung function tests. The proportions of patients treated with pirfenidone and nintedanib were no different (48% vs 57%) and the survival outcome did not differ significantly (38% vs 34% at 72 months, p = 0.63). Conclusions: ANCA-positive ILD patients with UIP pattern have some distinct features but show a similar survival curve to the ANCA-negative patients with IPF.

Background Idiopathic pulmonary fibrosis (IPF) with co-existent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may be associated with reduced FVC decline compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. Methods Visual emphysema extent (CPFE:non-CPFE: derivation cohort=317:183; replication cohort=358:152), scored on computed tomography imaging subgrouped CPFE patients using either a) 10%, or b) 15% visual emphysema threshold, or c) an unsupervised machine learning model considering emphysema and ILD extents. Baseline characteristics, 1-year forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) decline (linear mixed effects models), and their associations with mortality (multivariable Cox regression models) were compared across CPFE and non-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, 1-year DLco decline was a better indicator of mortality than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials. Results were replicated in the >15% emphysema population 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 comparable mortality associations. Conclusion When assessing disease progression in IPF, DLco decline should be considered in patients with >10% emphysema and a >5% 1-year FVC decline threshold considered in non-CPFE IPF patients.