Interstitial Lung Disease
Conditions
Brief summary
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.
Interventions
DIAGNOSTIC_TESTHRCT Thorax
HRCT Thorax at 0, 6 and 12 months
DEVICEGlycocheck Endothelial Glycocalyx Assessment
Measure of EG degradation using GlycoCheck Microvascular Health Score at 0, 6 and 12 months
DIAGNOSTIC_TESTBlood biomarkers
Endothelial glycocalyx degradation blood biomarkers and angiogenesis markers at 0, 6 and 12 months
DIAGNOSTIC_TESTPeripheral leucocyte telomere length
HT-STELA (High-throughput single telomere length assessment) at 0, 6 and 12 months
DIAGNOSTIC_TESTPulmonary function testing
Pulmonary Function Tests (Spirometry and Gas Transfer) and 6-minute walk distance at 0, 6 and 12 months
DIAGNOSTIC_TESTPatient reported outcome measures
Electronic collection of patient reported outcome measures
Sponsors
North Bristol NHS Trust
Royal United Hospitals Bath NHS Foundation Trust
Royal Devon and Exeter NHS Foundation Trust
University of Exeter
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Multidisciplinary team diagnosis of IPF or non-IPF fibrotic-ILD * Treatment naivety to anti-fibrotic therapy at entry to study * Adult ≥18 years \<85 * Informed consent
Exclusion criteria
* Forced expiratory volume in 1s/FVC \<0.7, * Significant other respiratory pathology including emphysema \>15% on CT (radiologist determined) * Evidence of ILD exacerbation at the time of CT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prediction of disease progression using multi-modal assessment | 12 months | Correlation of disease progression status (progressor vs non-progressor) with baseline markers including: 1. Endothelial glycocalyx health via GlycoCheckTM and blood biomarkers 2. qCT metrics 3. Peripheral leucocyte telomere length measured via HT-STELA |
| Feasibility of using qCT for disease prognostication and monitoring | 12 months | Recruitment, consent and attrition rates and dropout reasons |
| Endothelial glycocalyx | 12 months | III. Comparison of endothelial glycocalyx health between healthy controls and participants with fibrotic interstitial lung disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal disease progression | 12 months | Correlation of longitudinal change of pulmonary function testing: 1. Endothelial glycocalyx health via GlycoCheckTM and blood biomarkers 2. qCT metrics 3. Peripheral leucocyte telomere length measured via HT-STELA |
| Exploratory mechanisms | 12 months | Exploratory analysis of the data to infer causal mechanisms of disease progression |
| Prediction of disease progression | 12 months | III. Exploratory analysis of the ability of 6 month qCT and PFT change to predict progression at 12 months |
Countries
United Kingdom
Outcome results
None listed