Personalised medicine research for lung transplant patients secures funding

A study looking to develop a personalised medicine approach to antifungal treatment in lung transplant patients has been awarded funding by Pfizer and will be led by Dr Anna Reed, a consultant in respiratory and transplant medicine at Royal Brompton and Harefield hospitals.

Dr Reed’s research will be focusing on developing novel biomarkers to optimise how long antifungal treatment should be in patients who have undergone a lung transplant.

This study will use a personalised medicine approach and will combine detailed genetic information obtained from patient samples alongside other clinical factors.  This approach will help clinicians to identify non-invasive blood-based biomarkers to guide clinical decision making about optimal duration of therapy in order to:

-    treat disease effectively
-    reduce unnecessary drug side effects, and
-    minimise the emergence of drug resistance to therapies.

On average, patients live for 6-7 years after undergoing a lung transplant, with only 27% surviving after 10 years, which is relatively low compared to other types of organ transplantations.

The main causes of death after the first year of lung transplantation are infection and chronic lung allograft dysfunction (CLAD), which is term which describes a progressive irreversible decline in lung function.

Aspergillus is a type of fungus which in its most invasive form can cause infection that destroys the lungs. It is the most common fungus that infects lungs after transplantation and is associated with a high mortality rate.

Although it is thought that Aspergillus is linked to the development of CLAD, recent studies have shown that this is not clear cut, with some patients going onto develop CLAD and others not.

The current method of diagnosis of Aspergillus infection is difficult and is based on a combination of clinical, radiological, and lab-based tests. When a patient is diagnosed, they are treated with a long course of anti-fungal therapy which have many side effects and can lead to the development of drug resistance.

This is particularly a problem when Aspergillus is detected but may not necessarily causing CLAD, which may lead to patients receiving unnecessarily aggressive levels of antifungal treatments.

Dr Reed’s study aims to tackle this by identifying biomarkers which will determine whether a patient has eradicated Aspergillus infection effectively and whether Aspergillus is contributing to the development of CLAD. The study will involve compare blood and lung washings from lung transplant patients, both with and without CLAD, alongside those with and without Aspergillus. The samples will help determine if there are specific biomarkers which will help clinicians provide the right type of treatment to patients.

Dr Reed explained the importance of this research:

“This study builds on the immunophenotyping work we have been undertaking as part of an MRC-CARP funded study looking at immunological signatures of Aspergillus and CLAD in lung transplant recipients. The early data is extremely interesting with clear signatures of CLAD emerging. This Pfizer funded project will allow an additional layer of information to be developed and will provide more insights into diagnostics of Aspergillus in this patient group.

“In the longer term we aim to use these approaches to tease out the pathobiological pathways contributing to the development of all types of CLAD and this will inevitably provide new therapeutic targets to prevent CLAD in patients most at risk.”

The study is expected to begin in October 2022.

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