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A rapid, non-invasive, cost-effective, analytical device for bacterial or viral infection diagnosis through ultra-high sensitivity breath analysis.

Periodic Reporting for period 2 - BreathSpec (A rapid, non-invasive, cost-effective, analytical device for bacterial or viral infection diagnosis through ultra-high sensitivity breath analysis.)

Reporting period: 2018-05-01 to 2019-07-31

The world faces a growing epidemic of antibiotic resistance, however only two new classes of antibiotics have been brought to the market in the last 30 years. The discovery and development of new antibiotics is essential to maintain medical advances but poses significant scientific, clinical, and financial challenges, particularly for antibiotics active against Gram-negative bacteria (such as E.coli). Such bacteria have effective barriers against drugs, making treatment difficult, resistance likely and development costs and risks high. In addition, any new antibiotics brought to the market would likely be used cautiously to delay the development of resistance, adding an additional financial challenge in recouping the development costs. The O’Neill Report on Antimicrobial Resistance (AMR) identifies diagnostics as critical to the battle against antibiotic resistance.
This innovation action, BreathSpec, proposes a viable solution to the global problem of AMR through the final developmental stages of an existing diagnostic device, which will allow a rapid, binary decision to be made on the need for antibiotic treatment, and which with suitable optimisation will allow further differentiation and stratification to take place. The Innovation Action includes technical developments to optimise its function, data acquisition for the development of the decision-making analytical function and clinical validation.
It addresses these issues by producing reliable identification and quantification of key signature volatiles present in exhaled breath. It provides a non-invasive method for monitoring the volatile organic compounds present in an individual’s exhaled breath (and subsequently the blood) and has long been recognised as having significant utility as a clinical test that can be used for early disease detection and monitoring, and potentially to diagnose specific bacterial infections for better, more targeted use of existing antibiotics.
This innovation project has the following objectives:
• To optimise the design and functionality of the existing analytical device for the purpose of breath analysis for microbial volatiles, upgrading sensitivity and selectivity;
• To undertake multi-centre studies using healthy volunteers and patients with known pathologies to generate characteristic data for the production of algorithms to separate bacterial from viral infections;
• Undertake field trials to validate the optimised device with input from key stakeholders including full analytical and clinical validation;
• Generate analytical and clinical data to apply for the necessary regulatory approvals;
• Undertake value engineering and health economics studies to inform the commercialisation process;
• Initiate commercialisation of the product in target sectors/markets through our distribution channels and effective innovation management and dissemination.
A large-scale Breath analysis study was undertaken across the UK over a two-year period using the Breathspec ®. Following appropriate ethical governance and sponsorship (favourable opinion from the REC and fulfilment of requirements by the HRA) breath samples were collected at six NHS hospitals and two primary care GP practices across the UK.
GAS developed and produced 16 prototype BreathSpecs® to the project which were used in the clinical setting. Two devices were supplied to most locations to receive breath data in both positive and negative mode. The devices were tested and underwent rigorous QA/QC and were further developed based on feedback from the end-users within the project.
In excess of 1,100 subjects were recruited into the study over a 7-month winter flu season. Lower respiratory tract infection (RTI) and upper respiratory tract infection patients were recruited. Of these around 10% of upper RTI had a confirmed bacterial infection and the lower around 45% (due to subjects being recruited in Pneumonia clinics).
Safe data transmission protocols were developed to ensure GDPR compliance via an eCRF system. A state-of-the-art analytical pipeline for processing BreathSpec® breath data was also developed. Such data had a high dimensionality, but a lower information content. Data analysis techniques were developed to reduce the dimensionality and to improve indexing errors between samples and machines. This data was then applied to the BreathSpec® data, taking into account demographic/lifestyle variations (such smoking). Early results indicate that there is potential for the system to accurately state if a subject does not have a bacterial infection.
Based on the specificity of the study results, the health economics report undertaken shows that antibiotic prescribing could be reduced by 31% if a breath test was integrated into primary care diagnostics.
These results have been presented post project at the IABR, British Science Festival and reported in the UK Financial times. Further exploitation and dissemination activity is ongoing.
The development of the BreathSpec® has exceeded state of the art by undergoing significant development to make it a more user/patient friendly analytical tool. Feedback from clinicians and end users led to different design iterations in the BreathSpec® mount, user interface and sampling (mouthpiece holder) design. The BreathSpec® is currently the only commercially available breath analyser capable of robust deployment at the bedside for trace analysis of volatiles directly sampled from human breath.
The project is pushing the boundaries of cutting-edge technology by translating lab based volatile organic compound (VOC) analysis into a point-of-care setting. This novel approach can be regarded as trailblazer with the potential to be multiplexed for other medical diagnoses via the analysis of human breath and therefore a powerful innovation. The development of the prototypes and deployment in multiple settings, has never been undertaken on this scale before.
There are technical, commercial and socio-economic benefits to this project. It is anticipated that this rapid breath test with high predictive values, will be introduced into the EU as well as on a global scale with enormous positive impact on the socio-economic factors of patients. It is anticipated that the point of care nature of the device will have further socio impacts as its usability lends it to use in Developing countries where laboratory testing is not always possible.
As GC-IMS technology has very good predictive values there is an anticipation that the project would lead the way in fulfilling the market demand of improved antibiotic stewardship, generated in the UK and EU. The project outcomes and results anticipate meeting a very important healthcare need by:
•reducing unnecessary prescription of antibiotics in RTI and complements initiatives to improve antibiotic stewardship in the NHS – which could be up to 31% in primary care
•reducing the number of communities acquired pneumonias which leads to hospitalisation and even death with extensive costs to the NHS and related services – due to the point of care primary care test we will offer
An example of the device in function
BreathSpec demonstration in Zurich
The project presented at the ISOCS Annual Conference in Austria
BreathSpec Logo
BreathSpec offical panel and reveal at MediWales Connects 2019
The devices in the production line
BreathSpec device and staff during the clinical trials in Wales
Project Banner (2)
BreathSpec demonstration in Kiel
BreathSpec demo at the Breathomics in Manchester
Project Banner (1)
The Project presented at the PITTCON19
BreathSpec Device
Final BreathSpec device
BreatSpec stand in Kiel