Dr Anna Reed, consultant transplant physician at Royal Brompton and Harefield Hospitals, has been awarded funding through the Medical Research Council (MRC) Clinical Academic Research Partnership (CARP) programme for her research into fungal infections.
The CARP scheme supports NHS consultants to participate in collaborative, high-quality research partnerships with established academics.
Thanks to the funding Dr Reed will now have protected time to carry out her research which focuses on fungal infection in patients who have undergone a lung transplant.
Fungal infections and lung transplantations
On average, patients live for an average of 6-7 years after undergoing a lung transplant, which is relatively low compared to other whole organ transplantations.
The two most common causes of death are infection and chronic lung allograft dysfunction (CLAD), which is when a transplanted lung does not achieve or maintain normal function.
Aspergillus fumigatus is a filamentous fungus which in its most invasive form can cause infection that destroys the lungs. Aspergillus is associated with high mortality after lung transplantation. It can also colonise the body which means the fungus is present but not causing disease.
Although it was previously thought that colonisation by Aspergillus was 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. It is not currently possible to predict which patients will develop CLAD.
Given the high risk and mortality associated with progressive CLAD post lung transplant, clinicians continue to treat Aspergillus aggressively with antifungal medication (tri-azole drugs) regardless of whether it’s an infection or just colonisation. These drugs are associated with significant side effects, long term toxicity and increasing resistance of Aspergillus to these medications.
Dr Reed believes it’s important to establish whether colonisation really does lead to CLAD in order to avoid unnecessary side effects of tri-azole drugs. Her study aims to compare blood and bronchoalveolar lavage fluid (lung washings) from patients who have had a lung transplant and group them into those who have CLAD and those who don’t, and also whether they have Aspergillus or no Aspergillus.
Dr Reed, in collaboration with Dr Darius Armstrong-James at Imperial College London and Professor Adrian Hayday at King’s College London, will attempt to identify biomarkers to work out which patients are most likely to develop CLAD in response to Aspergillus at an early stage. This will enable individual patient tailored therapies to specifically target those at risk, whilst reducing unnecessary treatments for those who don’t need it.
On receiving the award, Dr Reed said;
“This is a hugely exciting opportunity with the possibility of direct patient benefit within a short time frame. Aspergillus disease post-transplant is a complex problem with significant morbidity and mortality related to the disease itself and side effects of toxic therapies. I hope this study will pave the way for significant advances in the management of patients with Aspergillus disease following lung transplant and that these findings will additionally provide unique therapeutic insights that may benefit the vast numbers of people with chronic lung disease also living with Aspergillus.
“It is my aspiration to use this project as a springboard to the development of a sustainable research platform for the investigation of all drivers of CLAD following lung transplantation. Prevention of CLAD remains the Holy Grail of lung transplantation and I am thrilled to have this opportunity to contribute to increased understanding of the biological mechanisms underpinning this devastating complication for my patients.”
The project represents a unique collaboration between the Harefield Transplant Unit, the Department of Infection & Immunity at Imperial College London and the Department of Immunology at King’s College London.
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