Paediatrics

Understanding variation in the use and duration of non-invasive ventilation in paediatric intensive care units across the United Kingdom and Ireland

Supervisor: Dr Sarah Seaton (sarah.seaton@leicester.ac.uk)

Over time there have been changes in the respiratory treatments provided to children in paediatric intensive care units (PICU), moving from use of invasive ventilation towards non-invasive ventilation including high-flow nasal cannula therapy. A recent randomised controlled trial (FIRST-ABC: FIRST-line support for assistance in breathing in children) concluded that amongst children who required non-invasive respiratory support, use of high flow was no worse than CPAP (continuous positive airway pressure) when considering days until the child was free of all respiratory support. However, there are large variations between PICUs in the provision of non-invasive ventilation, with high flow use ranging from 5% to 40% of admissions.

Objective: Explore and quantify the potential reasons for variation in provision of non-invasive ventilation between PICUs

Methods:

1. Epidemiological analysis of large-scale data routinely collected from PICUs to explore the variation in use of high flow after accounting for differences in the children (e.g., age, diagnosis). Likely statistical approaches could include logistic/binomial regression and hierarchical modelling.

2. Survey study of each PICU to understand differences in current policies which may explain variation

3. To explore if variations in use of non-invasive ventilation have led to differences in children’s outcomes (e.g., survival and length of stay)

Identifying novel therapeutic targets in glomerular disease- a multi-omics approach

Supervisors: Professor Jonathan Barratt (jb81@leicester.ac.uk) and Dr Haresh Selvaskandan (hs328@leicester.ac.uk)

Glomerular diseases are an important global cause of kidney failure in children and young adults and there are few effective and safe treatments for most of these diseases. By combining whole gene sequencing, single cell transcriptomics and imaging mass cytometry it is now possible to study complex kidney diseases in an unprecedented level of detail, offering the opportunity to identify novel biochemical pathways associated with disease. In Leicester we have access to an extensive biorepository of clinical samples, from local, national and international studies in glomerular disease and from our collaborators in Paediatric Nephrology. We work closely with the pharmaceutical industry on drug discovery studies, including joint PhD studentships, and have a number of in vivo models available to us to test novel therapies. The ACF will work on a study, in a glomerular disease of their choosing, that combines wet lab -omics training alongside bioinformatic training with our collaborators at The European Bioinformatics Institute (EMBL-EBI), Cambridge. The ACF will be trained by post-doctoral scientists who have extensive experience of training Specialised Foundation Doctors, NIHR ACFs (Adult and Paediatric Nephrology) and NIHR CLs. All completed NIHR ACFs have successfully been awarded personal training Fellowships (MRC, Wellcome Trust, KRUK).

Portable oscillometry in the diagnosis of asthma in children with preschool wheeze

Supervisors: Dr Erol Gaillard (eag15@le.ac.uk) , Dr David Lo (dkhl1@le.ac.uk) & Prof Damian Roland( dr98@leicester.ac.uk)

The problem:

Severe wheezing attacks are common in preschool children and result in frequent emergency department visits and hospitalizations. This is a significant health care burden worldwide. Our current strategies of management of preschool wheezing disorders are ineffective.

Unmet need: Diagnosis and biomarkers

A key problem is the lack of a diagnostic test because young children are rarely able to perform spirometry. Portable oscillometry is a new technology that shows promise in preschool children. Oscillometry measures airway resistance and impedance and an increase in both parameters is associated with asthma. The test is quick, non-invasive and importantly does not require any effort on the part of the child.  Additionally, further phenotyping is required to establish the best way to treat preschool children. Many do not respond to corticosteroids. Objective biomarkers and the assessment of treatable traits including allergic sensitisation, and an assessment of airway infections are needed.

Research plan: Observational study recruiting children with acute preschool wheeze from children’s ED, obtain oscillometry measurements pre and post bronchodilator and phenotype severe preschool wheeze on the basis of blood biomarkers and airway infection to pave the way for a clinical trial.

The ACF will also be expected to complete a systematic review.

This project fits with the research strategy of the Biomedical Research Centre especially with the biomarker and phenotyping in respiratory disease theme and the respiratory infection theme

We hold an NIHR fellowship (data focussed) in the department (Dr Lo) in the field of preschool wheezing. We also have international collaborations with leaders in the field of oscillometry and lead the UK nationally in the implementation of objective testing to diagnose asthma

Congenital diaphragmatic hernia

Supervisor: Dr David Lo (dkhl1@le.ac.uk)

Congenital diaphragmatic hernia (CDH) is a life-threatening congenital anomaly, with an incidence of approximately 1:2,500 live births. Mortality rate remains around 40–50% and in follow-up studies, multiple complications including pulmonary damage, cardiovascular disease, gastro-intestinal disease, failure to thrive, neurocognitive defects and musculoskeletal abnormalities have been described.

Despite this, there is no consensus on how these children should be monitored long-term. Previous follow up studies have also been based on small case series’ and there is limited longitudinal data beyond the first 3-5 years of life.

Objectives:

1. To describe the current follow-up arrangements for CDH in UK tertiary paediatric centres
2. To explore long term outcomes relating to CDH in children using a large primary care database linked to hospital data

Methods:

1. Survey study of UK tertiary centres
2. Epidemiological study using routinely collected health data

Rationale:

1. Identify whether there are differences/inequalities in the way children with CDH are managed in the UK.
2. Describe long-term prognosis of children with CDH from birth to early adulthood
3. The above information will be utilised to inform the development of consensus guidance for the follow-up of children with CDH