East Midlands Breathomics Pathology Node

Stratified medicine is an approach which subdivides patients with a shared disease into groups based on, for instance, their risk of the disease progressing or how they respond to treatment. Identification of these different groups can help predict the most effective and safe intervention for individual patients. In addition, by understanding the underlying mechanisms that cause these differences, researchers can develop new interventions for those groups whose needs are currently not well met.

Molecular pathology is a major tool in stratified medicine. Tiny samples of blood or tissue are taken from the patient – usually with minimal discomfort because of the small amount taken and the use of minimally-invasive methods of collection. The samples are then analysed for levels of large molecules (such as proteins and DNA). Combining these results with other information, such as imaging and clinical data, enables the precise subdivision of patients.

To support molecular pathology, the MRC and EPSRC have supported six nodes led by the universities of Edinburgh, Glasgow, Leicester, Manchester, Newcastle and Nottingham. Each node brings researchers, clinicians and industry together to develop molecular diagnostic tools, to enable stratification, in disease areas such as cancer, respiratory diseases, digestive disease, infections, rheumatoid arthritis, psoriasis and lupus.

The East Midlands Breathomics Pathology Node (EMBER) is one of the six supported nodes, hosted at the University of Leicester with partnerships with Loughborough University and Industry.

EMBER is to develop novel breath-based systems for molecular pathology. Exhaled breath contains volatile organic compounds (VOCs) that reflect biological processes occurring within the lung and, via the vena cava, more distant organs. Analysis of VOCs in breath provides rapid, at-patient and in clinic non-invasive approaches for diagnosis, phenotyping and stratifying patients. Importantly the range of clinical conditions is large and includes: respiratory infections, cancers, respiratory disease such as asthma and chronic obstructive pulmonary disease, and cardiovascular disorders such as heart failure.

The East Midlands has a unique and congruent group of clinical and analytical researchers drawn from the University of Leicester (UoL), the University Hospitals of Leicester NHS Trust (UHL) and Loughborough University (LU) with strengths in clinical research, analytical chemistry, data management and mathematical modelling of complex data. EMBER focusses these combined strengths, and co-ordinates existing collaborations with industry partners to create a nationally-leading centre in “Breathomics” with the critical mass to establish world-class delivery of new technology, applications and training in molecular pathology.

EMBER will deliver near-patient and remote sensing technologies to analyse breath and by consolidating the assets and expertise across the consortia build an infrastructure that will result in novel methods to analyse complex “omics” data that will be applicable ultimately to many areas of diagnostic pathology; translated from EMBER‟s leadership in the analysis of breath signatures.

Why does it matter?

In 2012, there were almost 403 thousand deaths in the EU-28 resulting from diseases of the respiratory system, equivalent to 8.0% of all deaths. The proportion of deaths in the United Kingdom from respiratory diseases was considerably higher than the EU-28 average, at 14.1%.

Cardiorespiratory disease accounts for approximately 70 % of acute hospital admissions.

The diagnosis of undifferentiated breathlessness includes heart failure, community acquired pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), and asthma.

EMBER will help clinicians with improved diagnostics and biomarkers to predict response to interventions and natural history of disease. Patients will have improved clinical decision making with new near-patient, non-invasive technologies that are widely applicable with benefits extending to patient groups that present challenges for other molecular pathologies due to difficulties in accessing samples e.g. children and the elderly.

EMBER will help in improving the development of novel devices with clinical applications and the embedding this new molecular pathology in health care. We predict that EMBER's impact will therefore be transformative in developing high-quality biomarkers and analytical technologies with impacts upon economy and health.

Accurate diagnosis of acutely ill patients with multi-morbidity remains challenging. It is well recognised that when clinicians remain uncertain of the cause of breathlessness, patients have a longer hospital stay as well as increased morbidity and mortality.

To identify and evaluate the diagnostic and prognostic value of exhaled breath metabolomic biomarkers in acute cardio respiratory breathlessness and common indicator diagnoses associated with acute cardio respiratory breathlessness. Specific indicator conditions have been selected according to their (i) relatively high prevalence, (ii) high unmet need, mortality and morbidity and (iii) need to develop better diagnostic and prognostic algorithms in acute care pathways.

14.1 %

UK deaths are from respiratory disease

1 in 5

people in the UK has ever developed long-term respiratory illness

70 %

hospital admissions were for cardiorespiratory diseases

10,000

people in the UK are newly diagnosed with lung disease

Our Aims

Management & Governance

To institute the management and governance structure of the molecular pathology node- EMBER comprising of three Institutions University of Leicester, University of Loughborough and University Hospitals of Leicester NHS Trust together with patient involvement and industry partnerships.

Analytical Pipeline

To optimise and technically validate breathomic technology, establish an analytical pipeline linked to a knowledge platform with data processing and modelling capability.

Embedded Clinical Validation

To undertake clinical validation of breathomics by embedding breath sampling into a clinical research programme to discover disease and phenotype-specific breath signatures in a test cohort, apply these signatures in near-patient devices in validation cohorts in acute and clinic settings with the breathless patient and lung cancer as exemplars.

Platform Integration

To extend existing knowledge management platforms to integrate clinical meta-data, with breathomics and other aligned omics.

Education & Training

To provide training to clinicians, allied health professional and basic scientists; to establish modules within MSc courses and new PhD programmes.

Enhanced Engagement

To engage widely with stakeholders- patients, clinicians, scientists, registration bodies, health care providers and industry to ensure successful and widespread adoption of breathomics into the clinic.