Prognostication and disease monitoring in fibrotic interstitial lung disease

Introduction Fibrotic interstitial lung disease (f-ILD) causes significant morbidity and mortality worldwide. Progressive pulmonary fibrosis (PPF) describes a cohort of patients who develop progressive disease despite standard treatment. To provide optimal care, it is vital to identify those patients at risk of developing PPF and those who are progressing despite treatment. The use of quantitative computed tomography (qCT) to analyse high resolution CT (HRCT) scans may enable more accurate prognostication and disease monitoring than current routine practice. qCT work to date has identified the pulmonary vasculature as a potential radiomic biomarker to address these issues. Methods A systematic review summarised the current use of qCT for prognostication and disease monitoring of f-ILD. A UK-wide service evaluation was performed to explore the use of nintedanib in the treatment of PPF and the criteria used for PPF diagnosis. The role of qCT was then explored in both retrospective and prospective methodology. Finally, two proof of concept studies explored the use of side-stream darkfield video-microscopy to quantify endothelial glycocalyx (EG) health in patients with f-ILD and a SPECT-CT scan of V3 integrin activity was used to image angiogenesis in f-ILD. Results The systematic review identified numerous high quality studies identifying a role for qCT in f-ILD but most were limited by retrospective methodology. The service evaluation identified that over half of patients commenced on nintedanib for PPF in the UK between November 2021 and September 2022 were diagnosed with PPF based on progressive changes on HRCT. The retrospective qCT work built a comprehensive database of 529 patients with f-ILD. In idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP), qCT is independently associated with transplant- and progression- free survival. In systemic autoimmune rheumatic disease related ILD, changes in qCT correlated with changes in pulmonary function testing (PFT) and ground glass quantification was protective for developing disease progression. In a prospective study, 36 patients underwent serial qCT alongside PFTs, patient reported outcome measures and 6 minute walk testing. Changes in qCT correlated with changes in PFTs and greater baseline extent of fibrosis measured on qCT was associated with higher risk of death at 12 months. EG assessment using side-stream darkfield sublingual video-microscopy was feasible and acceptable to patients with f-ILD. SPECT-CT using an V3 integrin ligand identified higher standardised uptake values in patients with fHP compared to healthy controls. Discussion The studies presented offer a comprehensive overview of the role of qCT in f-ILD. qCT is associated with disease progression and survival in both retrospective and prospective study. Assessment of systemic and pulmonary vascular changes may have a role in understanding the pathogenesis of PPF. Future study will look at incorporating qCT into routine clinical practice.<p></p>

Author dc:creator

• Giles Dixon (21065813)

• Interstitial lung disease
• Pulmonary fibrosis
• Artificial Intelligence

Statement dc:rights

• All rights reserved
• Open Access after 2027-05-22

Identifier

10779/exe.32362071.v1

OAI identifier oai:identifier

oai:figshare.com:article/32362071