Title: The Inspired Sinewave Technique: a novel technology for the diagnosis and assessment of Chronic-Obstructive Pulmonary Disease
Funder: Department of Health and Social Care

Abstract: Background The Inspired Sinewave Technique (IST) is a novel device to noninvasively measure cardiopulmonary function. Potential clinical applications range from monitoring cardiac output for fluid management in the operating theatre to assessing lung function for disease in outpatient settings. The technology has been developed through the proof-of-concept phase and clinical feasibility phase, supported by the Engineering and Physical Sciences Research Council and the NIHR i4i. Under the clinical feasibility phase, we have successfully demonstrated the IST s capabilities in all 3 proposed clinical applications: intraoperative fluid management, optimising ventilator settings in intensive care, and lung function testing in outpatients. At the same time, we also demonstrated the commercial feasibility of the device with its drafted business plan being voted twice as finalist of the OneStart competition &ndash; one of the biggest life-science business plan competition in Europe, judged by industrial experts from Johnson & Johnson and GSK among others. Taking the panel feedback from our last year unsuccessful NIHR application, we have decided to focus the development of the IST on the assessment of patients with chronic-obstructive pulmonary disease. In the UK alone, COPD kills 30,000 pa and healthcare costs are expected to rise from &pound;1.5bn (2011) to &pound;2.3bn (2030) with half of the cost coming from the management of symptom exaberation/hospitalization. This warrants efforts to develop better testing tools that will lead to more effective management, improved patient outcomes, and reduced costs. Research question In the feasibility phase, we have shown in more than 100 COPD patients that the IST reliably staged COPD severity and had a stronger correlation with standard measures of symptom severity (COPD Assessment Test - CAT), in comparison with standardly-used clinical tests. Building on these evidence, the major research question we would like to address in this proposal is whether the IST is superior to spirometry and high resolution CT in predicting exacerbation. Aims and Objectives We therefore set the following objectives in the three aspects of the technology: Clinical: Build a large clinical data set to demonstrate that the IST is superior to spirometry and CT in predicting symptoms and outcomes. Build an economic model to show that the IST s superior predictions will lead to sufficient outcome improvements and cost savings, and therefore justify the capital required for adoption. Technology: De-risk the technology to the point that it can attract private investments, especially in the sensing unit development and clinicians usability. Business: Develop an investable business plan backed by an experienced management team. Timeline and Expected Output We aim to achieve the above objectives in three years, considering the time required to gain ethical approval and patient recruitment. At the end of year 2, we believe we will have sufficient evidence and materials to approach investors for follow-on funding. The project will be considered successful if, at the end of the project, the IST will have secured private investments for commercialization, and will have sufficiently been promoted and supported by the wider academic and medical communities.

Lay abstract: Measurements of lung and heart function are vital in the diagnosis and management of a wide range of heart and lung diseases. Ongoing monitoring of 'cardio-pulmonary function' can inform doctors if and when intervention is needed and how best to deliver treatment. It is unfortunate that there is still no accurate, reliable and easy way to monitor this, especially in sick patients and by the bedside. The commonest test is spirometry (&ldquo;the blow test&rdquo;). This measures how rapidly air can be exhaled. Perhaps not surprisingly this gives only limited information about such a complex organ. It's also not surprising that it is relatively insensitive to disease, especially in the early stages. It's also difficult, and sometimes stressful, to perform and so is disliked by patients. To address this unmet need, we are developing a new technology:- the Inspired Sinewave Technique (IST), which continuously measures/monitors lung and heart function. It also has the advantage of requiring only normal quiet breathing through a mouthpiece and is unstressful, and so preferred by patients. IST can address multiple unmet needs, including monitoring patients in Intensive Care, but we believe that its greatest impact will be in diagnosing patients with early chronic-obstructive pulmonary disease (COPD), which is the focus of this application COPD is a global disease, affecting >60M people, killing >3M annually. In the UK alone, 3M people are affected with 23,000 deaths/yr, making it one of the leading causes of death and the 2nd largest cause for hospital admissions. Moreover, currently 70% patients are living with the disease undiagnosed and 25% are mis-diagnosed. The current test, spirometry, is relatively crude in terms of how accurate it is, and the disease is often diagnosed late when symptoms are irreversible. The NHS has set out one of its main challenges is to identify patients with COPD much earlier in their disease pathway, not only to improve patients quality of life but also to reduce treatment cost up to 90%. There is a need for a new technology to complement current practice. Under the previously-funded, ongoing NIHR project, we have successfully developed a working prototype that we have trialed on COPD patients in hospitals in Oxford. We have demonstrated that IST successfully detects and classifies the severity of COPD. As the next step, we would like to refine the device further and define a clear clinical pathway to ensure that the technology will make the greatest impact. We will work with the NHS and the Oxford Academic Health Science Network to achieve this. Finally, a technology would not make an impact if it is not available on the market. An Oxford University spin-out company is being set up to bring IST technology to the market.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY