Breathalyzers are a simple, convenient and affordable tool to measure the alcohol concentration in a person’s breath. What is often overlooked, is that exhaled breath does not only contain alcohol. In fact, it contains thousands of other components that originate from our blood stream and make their way into exhaled air. If those components can be analyzed precisely, could we use them as indicators for changes to our organism, e.g. caused by diseases like cancer?
The scope of breath analysis

Cancers are amongst the most research candidates for disease detection by breath analysis but many other slowly progressing diseases are under investigation, including heart disease, chronic lung disease, diabetes or Alzheimer’s disease. Even though the collection of volatile organic compounds to be investigated to make a diagnosis is likely to be specific for each disease, the underlying principle is the same: Detecting changes in a collection of volatile organic compounds and correlating them to the presence or absence of a specific disease.

The potential impact of breath analysis for disease detection

Breath analysis is said to have many potential advantages over existing medical tools. The sensor to analyze the volatile organic compounds could be miniaturized and integrated into small hand-held devices like an alcohol breathalyzer. Due to the versatility of the sensor technology, such a diagnostic device would not be limited to a specific disease but could be utilized flexibly for many different diseases and even to screen for multiple diseases at the same time. Such characteristics are likely to reduce the costs per test, eventually enabling the test to be performed more often on an individual patient and/or on a larger part of the population. In turn, this may lead to extended screening activities and convenient detection of diseases at early stage, way before any symptoms occur – a scenario that opens up not only opportunities but also challenges, both of which are discussed in this TED Talk: What your breath could reveal about your health.

Technology readiness and technical challenges

Breath analysis as described in the Lesson is not yet ready for commercial deployment and several challenges still need to be tackled. These include technical challenges such as the need for extremely reliable sensors and standardized breath sampling tools, but also the need for thorough validation in clinical trials and regulatory approval. Nevertheless, research and development on breath analysis is sky-rocketing and the numbers of currently active clinical trials involving breath analysis validation studies is remarkable as can be seen from this overview: Owlstone Medical - List of clinical trials involving breath analysis (Excel File).

One very specific example of a diagnostic breath test that has been successfully commercialized is the urea breath test to identify infections by Helicobacter pylori. However, it must be noted that this test differs from the ones described in the Lesson as it requires consumption of a specific reagent prior to the test and targets one single very specific volatile organic compound – and not a set of multiple compounds as described for detecting cancer.

Sensor technologies for breath analysis

The Lesson describes two very prominent sensor technologies that are being used for the detection of volatile organic compounds.

Firstly, the so-called ion-mobility spectrometry, an analytical technique that is used to identify ionized molecules based on their mobility through a gas phase. There are different concepts of how such a sensor can be designed. One concept that is frequently applied is the field asymmetric ion-mobility spectrometry (FAIMS) which makes use of the mobility of charged gaseous species under the influence of specific electric fields. See this Article on Wikipedia for more information.

Secondly, the Lesson describes the analysis of a mixture of volatile organic compounds using an array of chemiresistors. A chemiresistor is an electric resistor that changes its resistance upon contact with certain molecular species. An array is then composed of different types of such chemiresistors each having different chemical properties. The array typically does allow for the determination of the molecular structure of the chemical analytes. Instead, it produces a convoluted signal resulting from the interaction of all the volatile organic compounds with all of the different chemiresistors of the array. Such a signal can then be compared to adequate references using pattern recognition algorithms to correlate the signal with the presence or absence of a certain disease. An exemplary study of using such an array to detect a variety of diseases has been published in this Article

These are just two examples and there are other types of sensors and analytical instruments being used for the analysis of exhaled human breath. Each of the techniques has their own advantages and disadvantages and there are ongoing discussions which are the ones that are most suitable.

Fun Fact: Dogs that smell cancer?

It is well known that dogs have an extraordinary sense of smell. And there are several stories of dogs that can sniff out the presence of malignant tumors from a person’s breath. While it is still under debate whether dogs can actually be trained for this purpose, the theoretical possibility can be easily rationalized based on the effect that diseases may have on the collection of volatile organic compounds in exhaled human breath as described in the Lesson.

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