PRospective Evaluation of Interstitial Lung DIsease Progression With Quantitative CT

Study Purpose

The interstitial lung diseases (ILD) are a heterogenous group of conditions with varying degrees of inflammation and scarring (fibrosis) of the lungs. ILD progression is unpredictable, making prognostication challenging. A proportion of patients will develop inexorably progressive disease termed progressive fibrosing ILD (PF-ILD). Forced vital capacity (FVC), a lung function variable, is routinely used to monitor disease progression. However FVC can be a poor disease marker as it can be influenced by patient effort and can be difficult to perform. High resolution computed tomography (HRCT) is a necessary investigation for suspected fibrotic-ILD, making it a promising tool for research. A quantitative-CT (qCT) approach uses computer software to analyse HRCT scans and has advantage over visual radiologist assessments which are limited by inter/intra-observer variance. The investigators will undertake a feasibility study to determine whether baseline and longitudinal qCT can predict and quantify disease progression in fibrotic-ILD. The endothelial glycocalyx (EG) is a mesh-like layer that lines the small blood vessels. Injury to this layer has been implicated in non-thoracic fibrotic diseases. Telomeres are repetitive genetic sequences which cap chromosomes preventing their damage during cell replication. Prematurely shortened leucocyte telomere lengths (LTL) have been demonstrated in a wide range of ILDs. We will evaluate role of measuring EG health and LTL in disease prognostication. Adult participants with fibrotic-ILD from 3 centres in England will be recruited alongside healthy controls. Case (disease) participants will undergo investigations at 0, 6 and 12 months from recruitment including:

• - HRCT with quantitative analysis (qCT) - Lung function testing.

• - EG and LTL measurement.

• - Health related quality of life assessments.

The primary outcome will assess the correlation of disease progression status measured by standard of care (FVC) with baseline qCT and EG assessment. Healthy controls will only undergo EG assessment at all time points. Feasibility outcomes will be assessed including recruitment, consent and attrition rates. The results will inform a subsequent multi-centre study to assess the clinical benefit of disease monitoring with the measures assessed in this study.