A Breath of Fresh Research

The Porter team were out in force at the recent UCL Division of Medicine Retreat at Canary Wharf.

Most of the team presented their vital work and two well received projects were sponsored by Breathing Matters.

Dr Sharenja Ratnakumar presented the findings of a study summarised by Dr Hannah Torlot, the Breathing Matters Whitaker Clinical Fellow 2022.

The study aimed to tackle the treatment challenges associated with non-specific interstitial pneumonitis (NSIP) and explore the potential of using PET imaging to predict disease course and treatment response. They recruited 96 NSIP patients and utilized 18F-FDG PET/CT scans to measure lung metabolic activity. Among these patients, 13 underwent PET imaging before and after cyclophosphamide (immunosuppressive therapy).

The study findings revealed a significant association between higher background lung activity and increased mortality in NSIP patients. In the group treated with cyclophosphamide, the background activity to maximum uptake ratio (target background ratio–TBR) was higher in patients that eventually developed idiopathic pulmonary fibrosis (IPF).

[Figure show scleroderma associated ILD with NSIP pattern. Left panel shows inspiratory HRCT slice; right panel matched FDG PET]

The discussion around these results indicates that background lung activity may give an indication of underlying inflammation and a marker of disease severity. Additionally, the increased TBR observed after cyclophosphamide treatment in IPF patients may suggest that immunosuppression may be unfavourable in this patient sub-group. Consequently, these findings underscore the potential benefits of initiating anti-fibrotic treatment earlier in this specific patient population.

Overall, this study provides valuable insights into the management of NSIP, demonstrating the potential use of imaging techniques as indicators of treatment response. Further research in this domain holds the promise of refining the timing of therapeutic interventions and ultimately leading to improved patient outcomes.

 

Dr Emma Denneny, the Breathing Matters Whittington Clinical Fellow, also presented some exciting work.

Many individuals experience long-lasting health issues after recovering from COVID-19, but we don’t fully understand why, which makes it hard to develop effective treatments. Researchers have studied the proteins in the blood during the early stages of the disease and identified biomarkers that help stratify patients by disease severity and provide potential targets for treatment. We hope to apply this approach to understand long COVID better, a complex and poorly understood condition, and identify individuals who are more likely to have persistent symptoms. 

In our study, we took blood samples from 138 patients attending the UCLH COVID-19 follow-up service and we used a special technique called mass spectrometry-based proteomics, to identify the proteins present in the blood and learn about their unique features. After that, we analysed the data using specific software to find meaningful patterns and information. 

We are particularly interested in identifying proteins related to residual lung damage and common symptoms in long COVID, specifically fatigue. Out of the 138 samples, 78 were hospitalised and 60 patients were managed in the community. Those with residual lung abnormalities 3 months after infection were older males who required respiratory support in hospital and had more severe disease. Proteins identified in this group were related to lipid transport, vitamin metabolism, wound healing and inflammation, suggesting a role in immune dysregulation. Fatigue was more common in middle-aged women following COVID-19 infection in the community, and protein expression in this group was also suggestive of immune dysfunction. 

Further work will establish whether these identified protein patterns related to immune dysregulation, lipid metabolism and wound healing are consistent and reproducible. The ultimate aim is to identify and validate a specific set of proteins that can serve as a signature for well-defined groups of patients with long COVID. 

 

[May 2023]

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