A new revolutionary method has been developed by a European consortium of scientists to improve diagnosis of lung cancer, with clinical study centers in Innsbruck and Rostock. This quest was supported by the European Commission in the project BAMOD. Detecting cancer markers in human breath has been a long-standing, but not very public ambition. For at least a decade many researchers around the world have been trying to find such revealing information in concentration patterns of volatile compounds in exhaled breath. The list of potential candidates has been combed for compounds signaling the presence of lung, oesophagus, liver and even breast malignancies early enough. Scientists aim to develop a non-invasive, safe and quick diagnostic tool of high predictive value, which would pick up any minimal abnormality in good time. Of course, any such test would have to meet the criteria of specificity and sensitivity.
Mass spectrometry is a well-established method, albeit expensive in the first place, and combined with gas chromatography it can yield highly accurate results. In the BAMOD lung cancer study several different analytical techniques have been combined in the search of volatile compounds in exhaled breath. Besides lung cancer, a BAMOD partner team from London’s Imperial College has been trying out just one analytical technique aiming to spot oesophageal cancer in good time. This trial is smaller than the leading one in Innsbruck and Rostock, which involves 400 lung cancer patients and 500 controls, but for both lung and oesophageal cancer, specificities and sensitivities around 80% have been achieved. However, there is still a long way to go to improve these promising pilot results to get a proper clinical test.
In their quest, scientists all over the world have been trying out other analytical techniques like sensors or sensor arrays. At the end of last year, an Israeli team also used carbon nanotubes coated with an organic material in a small study involving 15 healthy volunteers and 15 patients with stage 4 lung cancer. Each sensing device provided a unique response when exposed to the more than 200 volative organic chemicals present in human breath, and was subsequently calibrated for the experiment.
Previous findings suggested that alkanes and aromatic compounds are the main volatile candidates which might contain potentially useful information to identify lung cancer. A paper published by a team of Rome scientists back in 2002 detailed the screening of collected breath samples on 60 volunteers by means of an electronic nose, suggesting that the alteration of breath composition induced by the presence of lung cancer was enough to allow a complete identification of the diseased patients. But the cancer stage at which the disease might be identified was not evaluated.
Some other tumours would not appear to be the obvious candidates to be detected through breath, but in 2003 a team of New York scientists looked for volatile markers of oxidative stress, which has been implicated as a risk factor in breast cancer, and concluded that they appeared to provide a sensitive and specific set to detect this malignancy as well. Again, alkanes were taken prominently into account. To the researchers, they appeared to be a more reliable marker of oxidative stress than pentane alone.
Higher levels of breath pentane that had been previously found in women with breast cancer, however they were also present as a nonspecific marker of oxidative stress in a variety of other conditions including rheumatoid arthritis and schizophrenia. The quest to ringfence marker candidates continues, in mathematical form too. For instance, a recent University of Innsbruck paper published a new algorithm for identifying breath gas marker candidates in liver disease.
(5 May 2009)