The Leicester Royal Infirmary’s Diagnostics Development Unit, launched in October 2011, is the result of a collaborative effort between researchers spanning several departments in the University of Leicester – including chemistry, space science, physics and astronomy, engineering, cardiovascular medicine and IT services – and clinicians at the infirmary.
The unit has been designed to detect the ‘sight, smell and feel’ of disease in real-time without the use of invasive probes, blood tests, or other unpleasant and time-consuming procedures that can lead to infections, complications and false positives.
Mark Sims, professor of astrobiology and space instrumentation at the University of Leicester, who co-led the project, explains: ‘In the old days, it used to be said that a consultant could walk down a hospital ward and smell various diseases as well as telling a patient’s health by looking at them and feeling their pulse. What we have done is develop a high-tech version of that in order to help doctors to diagnose disease.’
Many illnesses show signs that can be measured outside the body and could, in principle, be diagnosed by the unit. Liver disease, skin conditions, allergies, asthma and cardiovascular are obvious ones but bacterial infections, gynecology problems, drug and alcohol-related problems, and cancer could also be usefully diagnosed at the unit.
By integrating noninvasive methods, the researchers hope this will speed up diagnosis, leading to better outcomes for patients.
The A&E unit
The unit comprises a bed in the hospital’s accident and emergency (A&E) department surrounded by three suites of noninvasive technology. The patients, at worse, have electrodes attached to their body and spend just 20-30 minutes undergoing a battery of tests.
One suite comprises several monitors for measuring cardiovascular activity, and will flag up heart and respiratory problems. A thoracic impedance monitor measures how well the heart is working; an electrocardiogram analyses heart rhythm; and trans-cutaneous devices measure oxygen and carbon dioxide levels in the blood.
In the second suite are instruments that analyse, in real-time, the concentration of gases/metabolites present in a patient’s breath. Breath contains trace levels of compounds, which are the products of normal metabolism or metabolic pathways that have altered owing to disease.
Some breath compounds have already been linked to certain illnesses. Increased acetone levels in a person’s breath, for example, may indicate diabetes, while acetonitrile is associated with cigarette smoke inhalation, and nitric oxide is a marker for asthma. Certain sulfides have also been linked to liver disease and organ transplant failure. In a specific test, increased levels of carbon dioxide can be an indication of infection by H. pylori, which is associated with peptic ulcers.
This suite includes a spirometer, which measures the volume and speed of breathing; a capnograph which monitors carbon dioxide, and there is also an NO analyser. The real-time analysis of volatile organic compounds (VOCs) in breath is done by using variants of mass spectrometry – for example, proton transfer reaction-MS (PTR-MS) and selected ion flow tube-MS (SIFT-MS) – which were developed by Paul Monks, professor of atmospheric chemistry and member of the project team, and his colleagues in the university’s chemistry department.
The third suite employs imaging systems, some of which were developed by the university’s space science programme. The technology is used here to analyse light coming from a patient’s face, hands and other body areas, which may indicate signs of disease, such as infection, cancer, rashes and allergies. There is an infrared thermal imager, which can detect a patient’s peripheral and core temperatures; a multispectral imager, which measures changes in a patient’s colour very quickly; and a hyper-spectral imager, which detects more subtle changes in pallor, such as the yellowing of the skin as a result of liver problems.
As well as detecting early stage bruising and skin cancers, the imaging technology can tell whether circulation in the extremities is shutting down due to medical shock.
Benefits of an integrated approach
While most of the technologies in the unit have been used before in some way, they have never all been used in an integrated manner on so many patients. Combining instrumentation could be particularly important in detecting such conditions as sepsis, which exhibits a number of different effects on the body and is hard to detect at an early stage, the researchers say.
‘Emergency care comes down to putting together a jigsaw of information to create a picture that gives you the diagnosis,’ says one of the project’s co-leaders, Tim Coats, professor of emergency medicine at the University of Leicester and head of accident and emergency at Leicester Royal Infirmary. ‘We hope that this sort of technology is going to give us more pieces of the jigsaw to make that picture clearer earlier on.’
The idea is to use the diagnostics development unit on the large volume of patients that pass through the A&E each year – initially in limited clinical studies of infections, sepsis and heart failure – in order to correlate measurements with traditional diagnosis and build up accurate signatures for particular disease states, thereby honing its accuracy. ‘Using a systems biology approach to integrate together different types of information may give patterns that using just a single instrument may not show,’ says Coats.
Ultimately, the researchers say they would like to move towards developing a series of hand-held devices. In the meantime, the diagnostics development unit will provide doctors with more information in real time to make a diagnosis, says Monks. ‘For example, if someone comes in who is breathless, it could be a heart attack or it could be asthma – it is very difficult to diagnose. But this system will be able to tell holistically, seconds later,’ he says. Rather than replace doctors, says Monks, the unit will augment, speed up, and increase the certainty of diagnosis.
The unit, which can monitor patients in critical condition, is also suitable for the development and testing of novel diagnostic and monitoring devices. While it will be used initially in emergency ‘medicine, Coats says it could also be valuable elsewhere in hospitals and in GP surgeries and perhaps even in a future generation of ambulances. ‘We are talking to industrial partners who might get involved in commercialising this work as the project matures,’ he said.
But not everyone is happy. Some critics argue that relying on machines can be misleading and there can be no substitute for ‘old fashioned’ examination of patients.
Anne Savage, a retired general practitioner, says: ‘I am very much for using sophisticated investigations and even blood tests as an adjunct to clinical medicine, but time and again people have been misled. Doctors are relying too much on tests. Instead, they should examine patients.’
She continues; ‘There are far better and cheaper ways of diagnosing disease. The investigations sound scientific but they can be misleading, the more so because people believe a machine can’t lie. Maybe it can’t, but the human body has a will of its own.’
Not losing sight of the human
However, Coats argues that the ‘old fashioned examination’ can also be misleading. ‘In fact if you look at the statistical accuracy of physical examination it has a poor sensitivity and specificity and often leads to error. Hence our need for better methods of sensing the patient’s body state,’ he says. ‘It is important not to loose sight of the human who is in the middle of the technology – being a doctor is certainly about scientific and diagnostic skills, but patients also need humanity, caring and communication. Science and caring are not mutually exclusive, the Diagnostics Development Unit at the University of Leicester is simply trying to give the doctor better tools to do their job,’ he says.
Before the invention of invasive technologies in the 20th century, doctors would use the sight, sound, smell and feel of the body to make a diagnosis. ‘Invasive technologies have taken us away from these old skills,’ says Coats. ‘In a way the Diagnostics Development Unit is bringing us back to an old approach, but using right up to date technologies to sense the look and smell of disease.’
Emma Dorey is a science writer based in Brighton, UK.