At the moment, doctors still often base their diagnosis on blood testing, CT scans, and MRIs. The patient’s breath isn’t used, even though it contains a lot of information. Some diseases emit a very specific smell. The body’s metabolism adjusts in response to a disease. The breath is, as it were, a human exhaust pipe, in which you can smell that change. The eNose Company is a medical-technical company that has developed the Aeonose, which is able to ‘smell’ diseases quickly and effectively using sensor technology.
A simple breath test to recognise sick patients
The eNose Company (founded in 2013) has been operational as C-IT, The Early Warning Company, since 1998, and has a long track-record of developing technology based on scent analysis. Scent analyses were initially used in the field of security, for example to trace explosives, drugs, or chemical weapons. Later, they were also used in the food industry, to determine whether food had spoiled or was contaminated. In the medical field, however, the technique isn’t used on a large scale yet.
The Aeonose uses metal oxide sensors, comparable to sensors in the car industry that detect exhaust gas. The device smells, based on substances in the exhaled air, whether the patient has a disease. Exhaled air contains a large number (>1.500) of different volatile organic compounds (VOCs). These create a representation (breath profile) of the human body’s metabolism. Such a breath profile consists of a lot of data, and is analysed in order to recognise patterns. By analysing many breath patterns, you can ‘train’ an algorithm, and can run an unknown breath profile through it. It will then immediately provide you with a diagnosis. Because of the self-learning character of the algorithm, the system’s ability to distinguish between a patient and a healthy test profile increases as more profiles are analysed. Training the Aeonose is the trickiest part, and takes a lot of time. For each affliction, a new algorithm is needed. eNose Company develops the software for controls and communication (Daemeter and hAermes) in-house.
The eNose technology was at some point developed for the police, to track down cannabis farms. Despite offering enough possibilities for use in other sectors, a conscious decision was made to use the technique in the medical sector. A multitude of stakeholders that wait for each other to take the first step, strict laws and regulations, and a long time-to-market all couldn’t stop the entrepreneurs from rising to the challenge. After attracting their new CEO, André Elands, in 2012, the team had above-average knowledge of, and connections in, the medical field, which was a more determining factor for them than the amount of obstacles. That knowledge and those connections turned out to be of great importance.
Carefully constructing a scientific foundation
Contrary to other parties, The eNose Company deliberately chose to remain under the radar in order to first validate their claims scientifically, and reverse engineered by opposing large corporates. They have been solidifying their scientific foundation to that end since 2005. Only when validation studies can prove without doubt that they find differences in the breath profiles of sick and healthy people, and the partaking medical specialists have published about the findings in medical journals, will they publish a report on their website. At first, they used a rather scattergun approach and explored some 30 clinical applications. In these first two to three years they obtained good results, and simultaneously learned from their errors. Think, for example, of medication that suppresses the breath profile, or incorrect research methods and the influences of environmental factors.
Everything happened without money changing hands, and, at first, without applying for subsides. Sufficient financial scope was created with own funds, private investors, crowdfunding, and DT Ventures. Healthcare institutions were allowed to publish themselves in case of success, on the condition that they made the data and patients available to ‘train’ the Aeonose. The focus areas of the research were determined based on relationships, but primarily through external applications by medical specialists. The first pilot study into the application of the Aeonose as a diagnostic tool for diagnosing head and neck cancer commenced at Maastricht UMC+ (MUMC+) in 2013. The promising results were published at the end of 2013, in the scientific journal The Laryngoscope. In response to these first studies, The eNose Company was able to collect almost €400.000 for further research using crowdfunding, and market launch and pilots for other afflictions such as breast cancer, lung cancer, prostate cancer and bowel cancer were accelerated. In 2014, after long and intensive trajectories, their hardware was also CE-certified, and in 2015 The eNose Company received an ISO-certification.
Support for innovative diagnostics held back by current system
In 2016, the first multi-centre study into the application of the Aeonose for diagnosing lung cancer started at the Medisch Spectrum Twente. The study will finish soon and the results are expected to be published at the end of 2020. “On paper, a positive business case was created, in which the breath test was placed early on in the care process. Very logical, in theory, saving a lot of costs and increasing quality. But reality is more recalcitrant. Who will pay for these savings? Because less CT scans are required and less patients are examined unnecessarily, the profit of the innovation goes wholly to the healthcare insurer. But that party will have to create sufficient space for hospitals to obtain such innovations. Only a societal business case could provide a definite solution. “Shared savings” could solve it, but for that you need visionary directors, doctors and insurers,” states André Elands, CEO of The eNose Company.
Other obstacles emerged in the early detection of bowel cancer with scent analyses versus colonoscopies. This indication is even trickier to develop since early detection of bowel cancer in the Netherlands is done through population studies. In this, the law concerning population studies must be adhered to. Consulting VWS (advised by the Health Council of the Netherlands) and the RIVM is thus necessary. Only excellent clinical results will be able to change this process.
Despite promising results, many people didn’t believe in the Aeonose’s potential, and The eNose Company faced much resistance. People are slowly becoming convinced of artificial intelligence’s potential, but this was very different in the past few years. Computers were also often not powerful enough. The eNose Company was and is very innovative, which complicates acceptance. Elands: “We can only prove our added value and increase stakeholders’ knowledge through having the right connections and people that believe in us. Unfortunately, societal gain is not always the most important aspect of increasing the acceptance rate. The healthcare system in the Netherlands has some perverse stimuli when it comes to that. On the other hand, the Netherlands is a very suitable place to conduct research and develop new medical technology, thanks to the high level of expertise.” Over the past five years, The eNose Company has noticeably been increasing their support and creating ties with ambassadors. In the meantime, several partnerships of medical specialists have come on board as shareholders, and are convinced that this will be the diagnostics of the future.
Additionally, the Aeonose is still constantly being tested in several national and international research studies. The eNose Company thus has a unique database of scientific data at its disposal. At the moment, clinical studies are taking place in over ten Dutch hospitals. Collaborations are also taking place with renowned parties such as Harvard, Mayo Clinic and MD Anderson Cancer Centre in the United States. They are currently examining what needs to be done to better integrate the Aeonose in all hospitals later on. Gradually, they’re entering the phase in they must pull out all the stops to ensure a successful rollout. The eNose Company is also working on several indications, but is reserved in their claims. In September 2019, for example, a consortium of companies and hospitals, coordinated by The eNose Company, received a subsidy of over 1.2 million euros from OP Oost to prepare the Aeonose for rollout and regular use.
And now to follow through…
By now The eNose Company has about a hundred ‘noses’ in the field in Europe, the United States, and Asia. They are all parallel, focussed on a large number of afflictions, from tuberculosis to all kinds of cancer, from pulmonary embolisms to multiple sclerosis. As noted, marketing the Aeonose is sometimes successful, other times the business model surrounding the affliction stands in the way. Elands: “When research is difficult or expensive, or when operations are necessary to reach diagnosis, it’s a different story. If you can present a simple breath test as an alternative to that, medical specialists are definitely open to the Aeonose.”
Take thyroid cancer, whereby 60 to 80% of cases are operated on before the doctor is sure if they have cancer or not. And because the thyroid is partially removed, the patient has to take medication for the rest of their life regardless. Aeonose would help to lower the costs by preventing operations, and we see that the entire profession embraces the device. Because the research method is non-invasive, the patient benefits immensely. There’s a big difference between breathing into a device calmly for five minutes, or undergoing an (unnecessary) operation. By now, a multi-centre validation study into the application of the Aeonose for diagnosing thyroid cancer has commenced at all hospitals involved in the Dutch Thyroid Cancer Group.
In some countries – where medical specialists are employed by a hospital which sends bills directly to the government that reimburses them – it’s a different issue. If a new method of diagnosis is better in quality and price, they will use it tomorrow. In countries like Sweden and Finland, therefore, the Aeonose was immediately embraced. Now, they are part of the effort to ensure that the indication in other countries is going well, so the Netherlands cannot fall behind. Eventually, it’s necessary for medical specialists and trade associations to pick up promising studies and include them in protocols and guidelines. After all, indications don’t have to be low-hanging fruit, but the support must be as big as possible.
After the rollout of the first indication for bowel cancer in the Netherlands, The eNose Company is commencing parallel trajectories with other afflictions. In doing so, they are focussing on healthcare trajectories with a positive business case (healthcare benefits and cost reductions) and benevolent stakeholders. They are also in the process of marketing their products based on licenses in Finland, Estonia, and Sweden, with help of local agents. In three years’ time, we hope to be well-established!”
- Leunis N, Boumans ML, Kremer B, Din S, Stobberingh E, Kessels AGH, et al. Application of an electronic nose in the diagnosis of head and neck cancer. Laryngoscope [Internet]. 2014 Jun 1 [cited 2021 Dec 15];124(6):1377–81. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/lary.24463
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