Med-Tech Innovation News spoke to Professor Tim Higenbottam who has been working with Camcon to develop BiMOD, a respiratory device designed to enable better oxygenation in patients with breathing difficulties.
Give us some insight as to why Camcon developed BIMOD?
Often ideas are not fully translated into actions or devices for many reasons, but the most powerful have often been because we can make do with what we have. The COVID-19 pandemic, however, like a searchlight “lit up” an area of medical care which carries a fearfully high mortality rate.
Invasive mechanical assisted ventilation (IMV), or positive pressure ventilation of patients in respiratory failure was introduced by a German company Drager in 1911. Prolonged use of this medical assistance has been known to cause damage to the alveoli, the delicate structures of the lungs. It is in the alveoli where gas exchange takes place. To damage this area of the lung potentially contributes to high mortality rates.
In respiratory failure from pneumonia the mortality rate is as high as 40%. At the beginning of the COVID-19 pandemic this figure rose to 60% in the UK. The skills necessary to manage these technically challenging machines perhaps initially were not sufficient, but over the several months of the first lock-down improvement occurred and the mortality rate fell to comparable historical levels. In part this was due to the reduction of numbers of people placed in IMV machines.
This raises a fundamental question – are there simpler methods than IMV to support patients by enhancing the gas exchange in the lungs? This is the most common cause of respiratory failure and occurs when structural changes, either chronic or acute, prevent the inhaled air from arriving in the remaining normal lung that has a good blood flow. The resulting mismatch between ventilation and perfusion of the lungs leads to low oxygen levels in the arterial blood and accumulation of carbon dioxide. This matching between ventilation and perfusion is called good gas exchange, which is very important to maintain adequate oxygen and carbon dioxide levels in the blood. Failure to do so can lead to death.
How does the device work?
The BiMOD is designed to improve gas exchange in people who can breathe spontaneously. It achieves this by delivering a pulse of oxygen at the very beginning of the inhaled breath. This also enables the pulse of gas to flow at the same rate as the patient’s inspiratory flow rate. By doing so, the oxygen is entrained in the early part of the inhaled breath. This entrained oxygen enters the regions of the lungs that are best ventilated. In the case of injured lungs, it finds its way to those part of the lungs that are still unaffected by the disease. These are the best remaining sites for gas exchange. By adding a small pulse of nitric oxide (NO) at the same time in the breathing cycle as the oxygen, this vasodilator gas can enhance the blood flow to that region. This enhanced gas exchange has been established in COPD patients when breathing both oxygen and NO together.
With a prototype of BiMOD in a randomised controlled trial over three months, we have been able to show that pulsed gases, oxygen and NO, can be delivered at home as well as in hospital - with no serious adverse events. BiMOD enabled the treated group of respiratory failure patients to exercise for longer than controls and it reduced the level of carbon dioxide in the arterial blood, indicating improved gas exchange.
By relying on the patient’s inspiratory effort, the lungs are not exposed to the high intrathoracic pressure that is needed to “force” the air/oxygen mixture into the lungs, which can rupture the alveoli. It is safe to use even in the patient’s home.
What went into its development?
Back in 1981, we demonstrated that inhaled NO is a powerful vasodilator in the lungs of patients with pulmonary arterial hypertension. This finding led to the gas being used to treat neonates with pulmonary hypertension, a clinical indication that is authorised by the FDA. But in the presence of lung disease like COPD and pneumonia, NO can cause increased blood flow to poorly ventilated areas and this worsens gas exchange. For this reason, NO has to be delivered at the same time in the breathing cycle as oxygen and to the same well-ventilated parts of the lungs. This ensures increased blood flow in the lungs is directed to well-ventilated lung regions.
The value of this co-delivery of oxygen and NO enabled the excellent results in the COPD patients treated with the BiMOD prototype.
The machines to achieve these improvements in the gas exchange were large and commercial development could not be achieved.
Binary Actuation Technology can be applied to various devices, can you give us an example of this?
The BAT concept is based on the process of internal energy recycling which supports some fundamental benefits: very low energy consumption, zero holding current, long life and high-speed operation - hence very short switching time. It allows the controlled flow of gasses or liquids. The technology is scalable and has been developed into many different configurations, sizes and shapes.
For these reasons BAT found unique industrial applications in:
Oil industry where a gas flow controlling valve is placed in remote locations far away from any source of energy i.e., deep in an oilwell where a set of valves must work without any service or maintenance for at least 10 years.
Automotive industry on HGV pneumatic breaks supporting modern ABS systems where a dedicated high speed dual compressed air switching valve is placed in proximity of the wheels to control slippage of each wheel independently. In short, the system can stop a loaded truck on wet surfaces in a much shorter distance.
Cryogenic applications requested by the space industry required accurate doses of liquid nitrogen delivered at the right moment using very little energy. Initial tests have been successfully completed, and the next phase is in discussion.
Many medical applications can benefit from the BAT concept. Examples include very small implantable and programmable valves for Hydrocephalus sufferers; various conditions where a catheter needs to open or close in a controllable manner; a dedicated Silent Valve has been designed to be an essential part of any breath supporting unit.
What did you learn from other industries that can be applied in life sciences?
I have worked to develop inhalers for the treatment of asthma and COPD by reducing airway narrowing. These devices require the patient to coincide the start of their inhalation with the release of the treatment from the inhaler. This taught me the value of timing input of the therapeutic medicine in the first part of the inhalation so reach the best functioning part of their lungs thereby enhancing airflow to these normally functioning lungs.
During my time in Sheffield University, I led a Framework V research project called COPHIT in which we build a virtual lung to learn how best to deliver medicinal therapies and gases to the lungs. This pan-European study included Industrial and Academic Partners and was able to model the flow of gas and drugs into the lung and into the arterial blood. It accurately predicted the Pharmacokinetics of an inhaled asthma therapy.
What do you feel the technology’s effects on patients can have?
Our technology impacts the patient in having to breathe through the nose or through the mouth. Patients will only feel a slight push as the gas is released, as we use small volumes to add to the first part of inhalation. Our observations from initial tests with volunteers tell us that such gentle “puffs” delivered at the beginning of each breath reassures a patient and can act as a calming factor.
The clinician can choose a specific amount of oxygen or NO and this has never been possible before the BiMOD. The specific doses set initially, if certain procedure is enabled, can be automatically updated.
Our BiMOD monitors oxygen delivery in two different ways:
One way is by constantly monitoring SPO2 [define] and to maintain saturation within a required range, each dose can be easily adjusted by updated pulse duration. Please note that we can control pulse duration in a repeatable manner with very high portion of a millisecond accuracy and various dosing strategies can be adopted to do it.
The second method is based on constant monitoring and averaging the pressure at inlet of second (pressure) lumen of breathing apparatus: a nasal cannula or a face mask. Momentarily, pressure is changing constantly and are analysed via a pressure sensor and digital filter; in this way the beginning of the inhalation phase can be accurately predicted. But an averaged pressure level allows us to assess the overall balance of the amount of air requested and delivered. On this basis flow can be automatically corrected. It is not as simple as changing pulse duration, but it could be done. And as above, a certain strategy needs to be adopted to avoid a “hunting effect” where the system keeps changing oxygen doses to try and achieve ever changing parameters. With carefully adopted time limits and hysteresis of important parameters, this automatic precure can be made stable as required.
Can you give us some insight as to your plans in life sciences?
We (Camcon Medical) are aware of the unique power and versatility of our core technology and with that in mind, will be opening ourselves to partnerships with diverse companies across the whole spectrum of medical and other applications.
Anything else you’d like to add?
Only to say persistence is often the hallmark of success.
