Breathtaking work from CRiL will change healthcare for those with respiratory conditions
Healthcare is changing. Advances in medical technology will enable patients to stay better informed about their conditions in future and help guide the most effective treatments. Among those developing such technology is Cambridge Respiratory Innovations Ltd (CRiL), formed in 2013 by a group who saw a gap in the market for a personal respiratory monitor for people with conditions such as asthma and chronic obstructive pulmonary disease (COPD). The company is a finalist in the Medtech Company of the Year category – sponsored by Chesterford Research Park – in the 2018 Cambridge Independent Science and Technology Awards.
“We believed that there was a real opportunity to repurpose some technology we had seen used in other industries and develop it into a monitor,” CEO Jeremy Walsh tells the Cambridge Independent.
More than 400 million people across the globe suffer from chronic respiratory conditions.
But there are no personal respiratory monitors in use that measure lung function.
The devices that do exist are based on proxies, such as the colour of your blood or how hard you can blow. They are typically difficult to use and require the right technique.
“A doctor will use either a peak flow meter or a spirometer. In both you blow as hard as you can and there are techniques to get the correct reading from them,” explains Jeremy.
“If your asthma or COPD is bad, then using one of these devices can ruin your day. You can feel bad for a number of hours.
“Our challenge was to create a device that people could use every day to give them information on their lung function – but to do it with normal tidal breathing.
“That was our lightbulb moment. We wanted to enable people to use it easily at home in the same way that people with diabetes have a blood glucose monitor. They have transformed diabetes care – patients use them three or four times a day and we don’t have people having fits or collapsing anymore because diabetes can be properly managed or controlled.”
With respiratory conditions, monitoring is useful to understand when a patient’s condition is getting worse.
“Somebody with asthma, COPD or a number of other respiratory conditions can slowly deteriorate without knowing it because they can’t feel it,” says Jeremy.
“In the case of COPD they can suddenly have what’s called an exacerbation. They become very breathless and it can take days or weeks to get over it. They are quite often hospitalised.
“They often say, looking back, that they can see they were slowly deteriorating. But if they had gone to a doctor, there would have been no evidence to say they should intervene. We are providing that evidence.”
By simply breathing normally into the company’s N-Tidal monitor, patients will get a reading on their current condition.
“It will give them a traffic light warning that indicates that you are as good as you get, starting to deteriorate or moving into an area of concern, meaning you need to take action to prevent yourself going into hospital,” explains Jeremy.
A warning can enable patients to get early intervention.
“In the case of asthma, it’s often a case of increasing steroids to prevent the deterioration. With COPD it’s often infection-based so the treatment is antibiotics. Patients may start with a chest infection of some form, but it takes five to 10 days to bubble up, and they can end up in hospital for five days and go through a very distressing experience.
“The average cost for a patient that goes into hospital with a COPD exacerbation is approaching £2,000 for the healthcare system.
“The cost of intervening beforehand, when they start that deterioration, is well under £100 and they don’t go through that distressing experience. So this has cost benefits and a patient benefit.”
N-Tidal also has the potential to reassure.
“Respiratory conditions carry a lot of anxiety with them,” notes Jeremy. “People don’t know when they are next going to be ill. We can substantially reduce that, which is the background for why we wanted to go into this and what we are achieving from the clinical studies.”
CRiL has effectively reinvented and reinterpreted an expensive hospital device called a capnometer, which has been used for years by anaesthetists and paramedics to monitor exhaled carbon dioxide (CO2) to check that a patient is alive.
The technology has never been used for monitoring respiratory conditions – until CRiL collaborated with two other companies and, with grant funding from Innovate UK, developed an LED infrared CO2 sensor, which is both small and low-cost.
“The CRiL sensor is unique,” says Jeremy. “Unlike existing capnometer sensors, it is accurate throughout the respired CO2 range, it is not affected by condensation from moisture in the breath and it does not need calibration.
“You breathe through a tube and we flash an LED light across it 50 times a second. This particular frequency of infrared light – 4.3 microns – is absorbed by CO2. We have an emitter and detector beside each other and a reflector on the other side of the breath pathway.
“We know how much light we’re sending off and, by how much hits the reflector and comes back, we know the CO2 concentration exactly – and we know it 50 times a second.”
With a solid state LED sensor, and no moving parts, the device offers great stability and accuracy.
The output is a waveform – like a graph – and the shape of it is an indicator, or ‘biomarker’, for respiratory conditions, something clinicians worked out in the 1990s but which they had no means of measuring and interpreting.
CRiL changed that after developing a prototype with help from SBRI-Healthcare, an NHS England-funded initiative that helps companies develop innovative medical technology.
An exploratory clinical study in 2016 at Addenbrooke’s with COPD disease delivered more than 2,600 respiratory records, which enabled the company to automate the analysis of the CO2 waveform shape changes – a world first.
With more Innovate UK grants and another SBRI-Healthcare development contract, further studies confirmed that children can use N-Tidal and that the waveform shape differentiates between healthy people and those with a respiratory condition. It can also show the increasing instability in a person’s asthma before they have an attack.
And the NHS clinical team at Addenbrooke’s is just completing a larger study using N-Tidal to investigate how the waveform shape changes in advance of COPD exacerbations.
“For a person with healthy lungs, the waveform is close to a square,” explains Jeremy. “A person with COPD has an obstructed condition so the CO2 finds it much more difficult to come out. It builds up slowly and you end up with a kind of shark’s fin-type breath.
“The shape of the CO2 coming out changes depending on the state of the respiratory disease. For COPD, it’s a different shape if you’re approaching an exacerbation.
“So by analysing the shape we can determine whether people are deteriorating and approaching an exacerbation.”
So far, 200 NHS patients have used N-Tidal in clinical studies, which have explored asthma, COPD, breathing pattern disorders, congestive heart failure, pneumonia and cystic fibrosis. CRiL has collected more than 20,000 respiratory records, which it is using to develop predictive algorithms using advanced machine learning. These can be used for both the management of respiratory conditions and diagnosis.
“At the moment we have a fairly basic way of adjusting the algorithm,” says Jeremy. “We can foresee a more advanced way to personalise it so it becomes very particular to the person and you would just go through a training exercise at the start,” he says.
N-Tidal will offer up to 48 hours’ notice of an exacerbation for COPD patients, or an oncoming asthma attack – with the exception of those brought on by environmental factors like pollen or cat hair.
It is of use for monitoring congestive heart failure because it also presents as breathlessness. For those with the condition, fluid builds up in the lungs, prompting the heart to work increasingly hard to get oxygen in and CO2 out.
CRiL has filed four patent applications and is developing a connected version of its monitor.
“The information will be collected, sent to a database and be available for the doctor to look at,” says Jeremy. “A patient can opt to have that traffic light warning go to a carer or family member. If you have an ageing parent living on their own, you could get a text to say there’s been a red warning.”
With funding from the National Institute of Health Research, the connected monitor will be used in CRiL’s first regulatory clinical studies next year.
The company is developing different versions of its monitor.
N-Tidal C is the data capture device that will be available next year, and will help pharmaceutical companies with drug development.
N-Tidal B, the personal monitor for use in the home, is expected to be licensed for NHS use in early 2021, while N-Tidal A, for diagnosis, will be available to GPs and clinicians from 2021-22 and will help solve the challenge of diagnosing respiratory conditions like asthma, even in children.
“Independent health economics research indicates that the NHS will save £67million per year using N-Tidal to improve the management of COPD and £21 million each year with asthma,” says Jeremy.
Breathtaking stuff, indeed.