## 3 The Metabolites of EB Volatiles
### Potential Use of Breath Analysis in Different Diseases
#### 3.5.1 Oncologic Diseases  
Lung cancer (LC) is the leading cause of cancer mortality, accounting for 28% of the cancer related deaths [30; 82; 245]. The National Lung Screening Trial (NLST, USA) demonstrated that LC screening by low dose computed tomography (LDCT) scans reduced the lung cancer mortality rate by 20% [39, 82]. Currently, CT and bronchoscopy are the principal techniques used for lung cancer detection [39]. The diagnosis of early stage lung cancer is critical for the life expectancy of the patients as its five-year survival is around 58%-73% when lung cancer is diagnosed in stage I, but drops abruptly to only 3.5% for later stages diagnosis. Taking in account that only 15% of lung cancer cases are diagnosed at an early stage, more than half of lung cancer patients die within the first year of upon the diagnosis [245]. The main cause for this is that available diagnostic methods are not sensitive enough and, moreover, they are expensive and invasive. Also for this reason, prescription of these methods for diagnosis often happens during late stages of the disease [30, 245]. There are strong evidences suggesting that certain cancers can be detected by molecular analysis of exhaled air [30] and for that reason exhaled VOCs are promising candidates as LC biomarkers. These VOCs are emitted from the membrane of the cancer cells and/or from the surrounding microenvironment to the blood stream [16, 82]. The cancer-related changes in the blood chemistry are then reflected in measurable changes to the breath through excretion via the lungs [82]. Previous studies have shown that the breath VOC profile of LC patients differs from healthy subjects. The results of these studies indicated that the breath test might have future potential for the management of patients with pulmonary nodules [82, 245]. In fact, monitoring VOCs in the breath may rapidly become an interesting addition or an alternative to conventional medical diagnostics. This innovative approach could transform LC care and management by allowing non-invasive diagnosis, prediction of the metastatic potential of the cancer cells, adapting individual treatment, and monitoring therapeutic success [16, 246]. Table 1 gives several examples of EB studies applied to lung cancer using different approaches, including GC [85, 86, 87, 97], PTR-MS [30, 84] and several e-nose and sensor devices [82, 88, 89, 90, 91, 92, 93, 94, 95, 96, 98]. It is noteworthy to mention here that the colorimetric sensor array developed by [PERSON] _et al._ detects volatile, active compounds present in the EB of LC patients [91, 94]. Colorectal cancer (CRC) is the second leading cause of cancer-related death in Europe and the third in the USA. The search for new and non-invasive screening system with the potential for high patient compliance and of low cost is still continuing (reviewed in [247]). Two promising studies, however, should be mentioned: [PERSON] _et al._ compared EB samples from CRC and healthy patients using GC-MS and identified 15 discriminating VOCs [27]. In turn, [PERSON] _et al._ analysed EB samples from patients affected by several forms of cancer using GC-MS and a custom nanosensor array. They were able not only to discriminate between cancer patients and healthy controls (GC-MS), but also between different forms of cancer (CRC, breast, lung and prostate cancers) [101]. Gastric cancer is one of the most common causes of death from cancer worldwide. The lack of defined risk factors and the unspecific clinical symptoms often delay its diagnosis, leading to a poor prognosis and high rates of recurrence. The usual technique for diagnosing gastric cancer is the upper digestive endoscopy combined with biopsy and histopathological evaluation of the biopsy samples. However, this method is invasive, relatively expensive, and requires highly skilled medical staff. Therefore, it is necessary to find a simple and non-invasive alternative to this screening test.