Translating technology from the laboratory to the clinic: Breath analysis and SIFT-MS

Medical applications of breath analysis go back more than 2000 years to Hippocrates, who noted the link between breath aroma and disease. However, it was not until the end of the last century and beginning of this century that developments such as gas chromatography mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS) and proton transfer reaction mass spectrometry (PTR-MS) have helped to identify hundreds of volatile compounds in exhaled breath. More recently, the translation of technology from the laboratory into the clinic has led to the analysis of breath from patients with malignant and non–malignant diseases. While GC-MS and PTR-MS are largely qualitative techniques, SIFT-MS (developed at Keele University by Professor David Smith FRS and Professor Patrik Španěl) is both qualitative and quantitative. This allows the concentrations of specific breath markers, mostly volatile organic compounds (VOCs), in exhaled breath to be determined with accuracy and precision, and acceptable in clinical diagnosis. Breath sampling is non-invasive and can be achieved in real time with no discomfort to patients, including young children and frail patients. Hence, SIFT-MS has the potential to be a robust and valuable tool in support of clinical practice for disease diagnosis.

Management of lung cancer is an area where SIFT-MS has real potential. In the UK, just under 40,000 people are diagnosed with lung cancer each year. More important, it is the UK’s most common cause of cancer death for both men (24% of all cancer deaths) and women (20% of all cancer deaths). As early stage diagnosis is associated with increased survival rates, it is hypothesised that the detection of VOCs released by lung cancer cells would improve early diagnosis and prognosis. At present, assessment of a tumour’s response to treatment still relies heavily on imaging techniques such as chest X-Rays and CT scans. There is, therefore, great potential for a cheaper, on-line, radiation-free and non-invasive system that is capable of detecting and managing diseases, such as lung cancer. This is something that breath analysis and SIFT-MS may be able to offer in the near future.

Non invasive breath analysis—
Dr JosepSulé-Suso (right) with PhD student Abigail Rutter (left).   

Although much work has been carried out in the search for volatile biomarkers in exhaled breath of individuals with lung tumours, no single VOC or combination of VOCs have convincingly been identified. Over the last few years, we have carried out work at the Institute for Science & Technology in Medicine (ISTM) on the release of VOCs by lung cells in vitro. This research has shown that lung cancer cells have a VOC emission profile that seems to differ from their normal lung cell counterparts. These encouraging results are leading further work to unambiguously identify individual biomarker VOCs that could support lung cancer diagnosis. This should lead to the development and production of analytical instrumentation for real time breath analysis that could be readily utilised in hospitals and GP surgeries.