Initiated in the 1960s by Dr. Linus Pauling, research into the volatile organic compounds (VOCs) in human breath has enabled doctors to apply new science to traditional diagnostic teachings.

VOCs are organic chemicals that are gases at room temperature. These compounds are produced by human cells as part of our metabolic processes and transported via the blood to the lungs and kidneys to be excreted in the breath or urine. Viral or bacterial infection, cancers or autoimmune diseases can cause changes and patterns in the VOCs excreted by a person.

Doctors have observed that a patient with typhoid fever might smell like freshly baked bread, a patient with arsenic poisoning might smell like garlic, and with a pseudomonas infection they may smell of grapes. Some surgeons report that they can smell the presence of cancer when they open up a patient. This unique smell comes from the VOCs produced by the body. How can dogs sometimes sniff out skin cancer? Research has established that cancerous skin cells produce a different pattern of VOCs from healthy skin – and a trained dog can smell the difference.

The study of VOCs excreted by the body can provide unprecedented insights into health, wellbeing, and illness, and research is ongoing.  

VOCs appear in trace amounts as small as one part per billion in the breath. If we can detect VOCs in blood, urine or breath samples and correlate the pattern with diseases, this analysis could provide a non-invasive means to screen patients for health issues. Rather than a blood or urine panel, doctors may soon order a smell panel. 

A new frontier for cancer detection

Current screening methods for cancer are falling short. The modern medical approach for identifying cancer centres on imaging, like X-rays and fluoroscopes, combined with biopsies. For illnesses like skin cancers, visual information provides a clue.

In many cases, these techniques are costly and time-consuming, and their sensitivity depends on the size of the tumour. CT scans come with risks of radiation exposure and false positives, while MRIs have relatively low sensitivities. In the case of mammograms for breast cancer screening, the sensitivity of the test can depend on the age of the patient.

Since early detection is one of the main factors affecting outcomes for cancer patients, a better screening method could have a huge impact on public health.

VOC analysis techniques are far less invasive or non-invasive, and quicker and cheaper than traditional screening methods. This means they could be conducted at the point of care and rolled out in less economically developed countries, where resources are limited and populations have restricted access to physicians, thus transforming outcomes.

Strides forward

Ground-breaking research is showing promising signs that there might be a correlation between patterns of VOCs and the presence of certain cancers.

In 2010, Dr. Philips et al of Menssana Research found a set of VOCs present in the breath that distinguished patients with and without breast cancer with 78.5% specificity. Owlstone Medical currently is working with the NHS on breath analysis for colorectal and lung cancer detection. Dr. Cai et al, Jinan University, found breath analysis to have a 94% specificity. Dr. Herman-Saffar, Ben-Gurion University of the Negev analysed breath and urine and found a very high predictive value for breast cancer. 

“The good news is that we seem to have markers for the most prevalent and virulent cancers,” says William Wittmeyer, CEO of vapour analysis innovator Electronic Sensor Technology (EST). “That includes lung cancer, breast cancer, gastric cancer and colorectal cancer. There is some research to support the belief that we can detect cervical cancer via VOC analysis.”

Once experts have identified the existence of markers, the focus is on developing the technology to screen for them. This technology has the potential to revolutionise how physicians screen for cancer.

“While a faecal test might be a very effective way to screen for colorectal cancer, for example, a breath test could be conducted at a general health analysis. If this breath test could indicate colorectal cancer, it provides the physician with diagnostically actionable information,” explains Wittmeyer.

The potential applications for this technology go far beyond cancer detection: studies are showing that VOC patterns could be correlated with other conditions, from Covid-19 to overtraining syndrome in athletes.

Cancer alone has a devastating effect on society, and it is frighteningly prevalent. Breath analysis represents a new frontier of medicine presenting new opportunities to identify it earlier, act faster, and improve outcomes.

“All this progress is driven by a critical medical need,” says Wittmeyer. “We have a medical need to screen better for lung cancer and breast cancer, as well as soft tissue carcinomas like liver cancer.” The innovators addressing this medical need with ground-breaking technology are pushing forward the future of medicine by building on centuries-old observations.

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