To celebrate British Science Week at Royal Brompton and Harefield hospitals we’re highlighting some of the important work our researchers are tackling.
In this first instalment we asked Dr Anand Shah to share with us his research and the particular clinical challenges he’s addressing.
Dr Shah is a consultant respiratory physician at our hospitals with a specialist interest in lung infection and in particular, fungal respiratory disease. He is also an honorary senior clinical lecturer in the Department of Infectious Disease Epidemiology within the Medical Research Council (MRC) centre of Global Infectious Disease Analysis at Imperial College London.
Fungal diseases – a ‘hidden’ global problem
What I have always found satisfying about being a clinical researcher is the ability to take the problems I see and encounter in a clinical setting, back to a research environment to try and unpick the mechanism of disease, understand susceptibility or develop new approaches and avenues for therapy.
My interest in research began when I trained within respiratory medicine and I developed an interest in understanding what makes people susceptible to fungal lung infections, and potential strategies to improve outcome.
This led to an MRC clinical PhD fellowship where I examined the effects of immunosuppression (used in organ transplants), on the human immune cell response to Aspergillus fumigatus (the most common mould that causes lung infection).
When I completed my training, I returned to Royal Brompton hospital as a consultant in the Host Defence unit, with a particular focus on growing and developing our fungal lung disease service.
Fortunately, I am able to split my time between clinical work and research thanks to a recent MRC Clinical Academic Research Partnership Award, which enables me to continue research to improve outcomes in fungal lung disease.
Fungal lung infection remains a significant problem globally with an estimated 300 million people suffering each year. Fungal infections cause as many deaths globally as for example tuberculosis, malaria or breast cancer, but the disease receives little publicity and research is relatively underfunded.
Diagnosis is often challenging and at present there are only a few antifungal therapeutic options available and only one class of oral antifungal drug (triazoles).
To make matters worse, triazole antifungals are also used widely in agriculture, resulting in a global emergence of antifungal resistance which could have catastrophic consequence. For example, our research has shown that approximately 20% of Aspergillus isolates from individuals with Cystic Fibrosis are resistant to first-line antifungal drugs.
The impact of fungal infection critically depends on the body’s own immune response, and it is very clear that to ultimately improve outcome, we have to find ways to enhance or subvert the bodies immune response to achieve disease resolution.
At the moment I am working on a number of collaborative research projects within fungal infection, including understanding the current burden of fungal lung disease in the UK, identifying novel methods to improve diagnosis and detection of antifungal resistance, and crucially understand susceptibility to fungal disease and identify avenues for novel therapeutic strategies.
Working to improve outcomes
There a number of ways we are aiming to translate our research directly to improve outcome for patients. Firstly, it is important to highlight the burden of fungal disease in the UK to improve national services, commissioning and awareness.
At present, there is only one nationally commissioned centre for the management of chronic pulmonary aspergillosis in the UK. Given the clinical complexity we often see in these patients, it is important to have more highly specialist centres that have experience and expertise in diagnosing and managing fungal infection and driving clinical translational research.
Our lab-based research is working to translate clinical and lab based research directly into clinical practice. We have developed novel chip-based diagnostics to rapidly detect antifungal resistance and are aiming to translate this to clinical use.. We also are working to use machine learning of clinical and imaging data to improve diagnosis and to help identify novel targets in the human immune response for future clinical trials.
Clinically, we are also driving a number of quality improvement strategies to improve the use of antifungal medication through state of the art electronic health record data technologies to enable stewardship at scale with an aim to reduce the development of antifungal resistance and improve outcomes.
What is exciting at the moment is the number of new antifungal therapeutics that are now in the pipeline for development. Although the focus for these trials has predominantly been invasive fungal infection (often seen after chemotherapy for example) there is increasing interest in translating these into chronic fungal infection.
There has additionally been a drive to achieve precision medicine (tailored to a subgroup of patients, instead of a one‐drug‐fits‐all model) in a number of fields, with cancer medicine leading the way in developing immune targeted therapeutics to improve outcome.
I am hopeful that over the next 5 years, we will identify novel immune targets in particular groups of fungal lung disease and translate these into early phase clinical trials, which will be exciting.
You can also listen to Dr Shah speak about his research on our podcast.
Read the other posts in our British Science Week 2021 series: