The science of medical diagnosis goes all the way back to the ancient Egyptians. But despite this long history, techniques continue to evolve. Today’s methods include analysis of blood, saliva and sputum for viruses, DNA fragments, proteins and lipids, tissue, biopsies and specialist imaging. These new high-tech methods are a far cry from what was available to physicians only 30 years ago. While they offer significantly higher levels of accuracy and earlier diagnoses, they’re still far from perfect. These new techniques can be expensive, invasive and time-consuming.
Today, exciting new research is driving forward the future of diagnosis with a fresh approach, and one that offers rapid painless and straightforward point of care diagnoses: breath analysis has the potential to transform the way we detect disease.
Significant research is underway in breath analysis, and ground-breaking innovations are expected. Breath analysis may lead to non-invasive rapid screening for diseases as diverse as cancer and diabetes. As researchers continue to gather data and refine the technology, the sky is the limit when it comes to what the breath can tell us.
The technology
The fundamental questions include: how can we take a breath sample and identify what it contains when some compounds are present only in trace amounts – as low as one part in a billion – and how can we do it rapidly accurately and economically.
One method uses surface acoustic wave (SAW) sensors, built on the notion of resonant frequency.
“A SAW device is a high-tech turning fork,” says Bill Wittmeyer, CEO of vapour analysis innovator Electronic Sensor Technology (EST). “Like a turning fork, its resonant frequency is dependent on its mass and length. If you change the mass, you change the resonant frequency.
“In our instrument we separate the breath into its constituent gasses with gas chromatography. The gasses are condensed onto the sensor. These condensed gasses change the frequency of the detector. Because it was operating at such a high frequency, a small mass condensing on it would be detectable.”
EST’s champion product, the zNose, combines SAW analysis with ultra-fast gas chromatography.
“The breath sample is injected into the instrument to be separated into its constituent component gasses. The chromatography system can be likened to separating ball bearings by size using a Japanese pachinko machine. Small bearings quickly fall through the bed of nails to the collection point; larger bearings transit the bed of nails more slowly. The speed depends on the size of the bearing. Similarly in chromatography the speed of separation in a chromatography column is dependent on the size of molecule.
“The larger the molecule, the longer it takes to get through the column. You get a series of peaks corresponding to the retention times of the compounds present. Knowing the retention time for the molecules, you consult a library to identify the compound with that retention time.”
This technology has diverse applications, from detecting bomb impact positions to measuring water pollution.
“When you have a means of detecting compounds at trace concentrations, medicine is one area where there’s a large opportunity,” says Wittmeyer. “We can develop the breath pattern for healthy individuals. If the patients breath differs from that healthy pattern we can infer there is some change in metabolism and it may be a disease. Research has been able to establish by experiment and clinical trials that lung cancer, breast cancer, tuberculosis and other diseases can be identified through breath analysis.”
A breath of fresh air for diagnosis
“We are looking for rapid, non-invasive means of screening for anything,” says Wittmeyer. Compared to traditional methods of diagnosis like blood tests and biopsies, breath analysis is far less invasive.
In the case of heart-lung transplant recipients, Wittmeyer explains, breath analysis could be used to replace regular biopsies: “When you get a heart-lung transplant, they have to tune the drugs they’re giving you to suppress your immune system. They look at tissue biopsies periodically to see what’s happening in your lungs.
“Breath analysis is a means of seeing whether there is an immune rejection response taking place without having to do a tissue biopsy.”
When it comes to detecting diseases like cancer, scans and screening usually require expensive equipment and specialist operators, and they expose patients to potentially harmful ionizing radiation. By contrast, breath analysis can be done at the point of care and gives rapid results. For countries and communities without the resources to provide expensive equipment, this could be a far more accessible alternative.
The potential
“There has been a lot of work in this area, and it is still continuing today,” says Wittmeyer. At present, approved applications for breath analysis include H Pylori infection detection, bacterial overgrowth syndrome, lactose intolerance and fructose intolerance.
Many other applications are in the pipeline, and clinical trials are underway. Breath analysis research is focused on asthma, colorectal cancer, lung cancer, breast cancer and infectious diseases such as tuberculosis.
“Sepsis is one of the most difficult situations in hospitals. One third of the people who get a severe septic event die,” says Wittmeyer. “We did a study in the ER where we looked at the breath of people who were given a lactate test for sepsis. We found a very high correlation between the breath results and ultimate diagnosis of sepsis, with 85% ROC.”
Down the line, periodic breath analysis via the ventilator could be used to anticipate sepsis and improve patient outcomes.
While many of these applications are in the early stages of conceptualisation and testing, the future is bright.
“The potential is very large,” says Wittmeyer. “One of the big potential values is when we take a sample, we get a picture of all the compounds that are present.” This means breath analysis could eventually provide a huge amount of information about what is happening in the body such as how the metabolism is functioning or how it is affected by a pharmaceutical product.
The more data researchers compile, the more applications of breath analysis they unlock. As research into this area continues, the future of diagnosis is taking shape.
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