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Details of Grant 

EPSRC Reference: EP/T001186/1
Title: The Idealised Lung Clearance Index: tuning in to the silent years of cystic fibrosis
Principal Investigator: Ritchie, Professor GAD
Other Investigators:
Robbins, Professor PA
Researcher Co-Investigators:
Project Partners:
Cystic Fibrosis Trust
Department: Oxford Chemistry
Organisation: University of Oxford
Scheme: Standard Research
Starts: 20 January 2020 Ends: 31 July 2023 Value (£): 461,345
EPSRC Research Topic Classifications:
Instrumentation Eng. & Dev. Med.Instrument.Device& Equip.
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
09 Jul 2019 HT Investigator-led Panel Meeting - July 2019 Announced
Summary on Grant Application Form
This proposal deals with an emerging and disruptive technology known as molecular flow sensing (MFS) of human breath. MFS allows highly precise and accurate measures of gas flows and concentrations such that a simple non-invasive breath test can be used to detect the onset of early stage airways disease, potentially of great strategic significance as the societal and financial costs of chronic airways disease are huge. The difficulty in identifying the presence of early airways disease and tracking change in disease state (progression or regression) with precision remains a serious problem for both medicine and industry. The standard approach of spirometry (for example, measuring how much air you can breathe out in a given time) does not identify the presence of disease in the lung until the pathology is well established, and this limits the opportunity for early intervention before there is significant irreversible structural damage within the lung. However, it is very difficult to justify starting expensive therapies without clear evidence from a marker showing the early presence of disease. In industry, an ability to track changes in lung function with precision would reduce greatly the number of patients that need to be recruited for a clinical trial. In turn, this would significantly reduce costs and addresses a major bottleneck in the whole drug development pipeline. Finally, the cost of new drugs is such that it will be impossible to use them without first determining which patients will benefit most. The unprecedented precision and accuracy of MFS technology has the potential to provide an early marker of pathology through the measurement of the inhomogeneity of the lung and thereby address many of the issues highlighted above.

This proposal specifically relates to the development of MFS technology for use with pre-school children with cystic fibrosis where a "window of opportunity" exists for early diagnosis of lung disease and intervention. Here, there are two technical requirements: (i) to reduce the timescale for the breath test, and (ii) to reduce the size of the instrument. Requirement (i) will be addressed by incorporating trace amounts of an inert gas into the inspired air to allow the time taken for it to sample the lungs to be obtained contemporaneously with "air" breathing data. Requirement (ii) will be achieved by miniaturizing the MFS device while retaining sufficiently high enough precision and accuracy to realise measures of lung inhomogeneity.

The MFS method is the first that seeks to separate inhomogeneity in alveolar ventilation into a component that arises because of inhomogeneity in the way the lung inflates and another that represents the inhomogeneity in the amount of deadspace; as such, it has the potential to separate reversible from irreversible abnormalities in CF lung disease. The normally used Lung Clearance Index (LCI) cannot differentiate between irreversible structural damage and airway narrowing due to mucus secretion. This fact further highlights the disruptive nature of MFS technology.

MFS technology directly addresses the core need for better ways of measuring lung disease, both for the development of novel therapeutics and for better management of patients with existing therapeutic options. As more novel therapeutic interventions become available that directly target the dysfunctional CF transmembrane conductance regulator, the quantitative data using the MFS may prove suitable to establish whether novel CF drug treatments will impact lung function measurements over time in young children where early intervention with effective treatments could have the most pronounced long-term effect.
Key Findings
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Organisation Website: http://www.ox.ac.uk