A baseline measurement of healthy human breath could one day enable the routine diagnosis of disease from a single exhalation

The first baseline analysis of healthy human breath brings closer the possibility of routine diagnosis of disease from exhaled air. Over 70 volatile organic compounds (VOCs) have been identified by Pawel Mochalski and colleagues from the Austrian Academy of Sciences, who used headspace solid phase microextraction (HS-SPME) to pre-concentrate samples prior to their analysis by GC-MS.

Breath analysis for healthcare is a hot topic, with the ultimate goal being a device that can identify an illness from a single breath at your doctor’s surgery. Although this is still some way off, breath chemistry is used currently to monitor some conditions. Exhaled nitric oxide is used to keep tabs on asthma and tuberculosis (TB), while hydrocarbons can warn of the impending rejection of a transplanted heart.

Of the 74 VOCs identified by Mochalski’s group, 24 were hydrocarbons, 10 were ketones, eight were terpenes, seven were heterocyclic compounds and seven were aromatic species. Results were averaged across the 28 volunteers who took part in the study to allow for differences between subjects, though Mochalski admits that much bigger studies are required to take into account the variation in the larger human population. ‘Bear in mind that breath contains thousands of VOCs from many different sources,’ he says. ‘There is usually a certain background level that has a tendency to vary, particularly when one is dealing with ppt and ppq concentrations.’

Mochalski explains that environmental factors, including air quality, a patient’s diet and whether they smoke, can significantly distort breath profiles. ‘There’s a long way to go before these kinds of breath tests [for VOCs] can be commonly accepted by clinicians,’ he warns.

Paul Thomas of the University of Loughborough, UK, agrees that much work lies ahead, but praises Mochalski’s efforts to date. ‘This is the start of something that is of fundamental importance. We need thousands of samples like this one. It is tremendously important that we understand the nature of the standard basic human breath profile,’ he says.

Although point-of-care diagnosis of TB can currently be made by looking at nitric oxide on the breath, Thomas describes the markers of other diseases as more subtle. ‘It’s really important that we get a definitive, decisive, phenotypically-stratified baseline – for different genders, diets and social states,’ he says.

Mochalski’s work is not limited to breath, but also looks for VOC markers in blood, making the technology potentially useful for search-and-rescue applications. Currently sniffer dogs are used to search for injured survivors trapped beneath rubble, but an established VOC blood signature could be used to find human life by sniffing with mass spectrometry.

But both diagnosis and search-and-rescue applications of this technology rely heavily on instrumentation being portable, and not just sensitive. Additionally, the pre-concentration step required by Mochalski’s breath analysis method adds to the complexity of the technique. So just how far are we from a simple one breath analysis being part of our routine medical check-ups?

‘We believe that future breath tests should rely on a hand-held, one-button, real-time device that can be used by an unqualified person,’ says Mochalski. ‘Ion mobility spectrometry seems to be a very interesting technique in this context. It’s already being used for the field detection of chemical warfare agents and toxic industrial chemicals. Our preliminary studies aiming at using it for the detection of breath VOCs look very promising.’