Paediatric respiratory medicine

Genetics 

We have identified and characterised a number of PCD genes and candidate genes, improving understanding of motile cilia function, and improving PCD diagnostic testing. We are investigating the role of RNAseq to uplift genetic diagnoses in people with PCD and aim to automate the analyses for clinical application.  

Pulmonary infections

Using our 3D ciliated airway models, we identified a novel isoform of ACE2, the entry site of SARS-CoV-2 which is upregulated by interferon-β, and ongoing research is investigating its role in COVID-19 infection. We have shown that cilia motility prevents NTHi biofilm formation, and that treatment with nitric oxide augments antimicrobial activity against these bacteria. We are currently investigating cilia and influenza virus interactions. 

Airway models

Using our bio-reserve of cells from people with characterised lung diseases (e.g. PCD, CF, bronchiectasis) we generate living models which are used to investigate new therapies, environmental exposures and infections. To reduce need for patient primary cells for high throughput testing, we generate immortalised CRISPR-cas9 edited cell lines, e.g. DNAH5 edited cell line has typical PCD static cilia. 

Development and validation of clinical tools 

We developed and validated PICADAR which is used globally to predict likelihood of having PCD, identifying individuals who need testing. We have assessed the accuracy of diagnostic tests for PCD in a clinical setting and have developed international evidence based diagnostic guidelines for PCD and asthma. We led the development and validation of quality-of-life questionnaires for PCD (QOL-PCD) which are now translated into many European and non-European languages.  

Clinical trials

As one of the lead trial centres in the European Cystic Fibrosis Clinical Trial Network, our institution plays a pivotal role in the innovative research of CFTR modulators, which are redefining the therapeutic landscape for cystic fibrosis. We rigorously evaluate CFTR modulators—potentiators, correctors, and amplifiers—focusing on their effectiveness in improving lung function and enhancing patient quality of life. In the first multinational clinical trial, we showed that azithromycin prophylaxis halves the risk of pulmonary exacerbations in people with PCD. We are preparing for phase 1 and 2 trials for novel PCD therapies. 

Registries

We lead the UK National PCD Registry which allows us to monitor well characterised PCD patients longitudinally, giving us a better understanding of the success of therapeutic and management strategies, which could then be used to inform plans for subsequent clinical trials. We share anonymised data with international registries, such as the European PCD Registry and iPCD cohort. The data has made step changes in our understanding of PCD.  

Artificial Intelligence

Leveraging AI, we have developed machine learning algorithms designed to enhance the analysis of sleep studies, potentially obviating the necessity for more complex, invasive procedures. Concurrently, we are exploring the integration of machine learning to refine the interpretation of radiological images, with the goal of providing clinicians with enhanced diagnostic tools that can accelerate the development of timely and precise treatment plans. In PCD we have interrogated complex data sets and identified genotypes associated with more severe disease.  

Advances in asthma care

We are a lead centre in transforming the care of children with asthma and other causes of wheeze. We have provided evidence for the safe use of salbutamol according to as needed treatment regimens and promoted the increased use of more carbon neutral inhaler devices. Our hypothesis that an essential component of asthma is autonomically determined is now being investigated with our collaborators in exercise physiology.