Implementation of breathomics in health and disease.

The air we breathe is essential for a healthy live. Health and disease reflect in the exhaled air and already, diseases were linked to its scent. Breath contains both volatile organic compounds (VOCs), and non-volatile components (exhaled breath condensate (EBC), and exhaled particles (PEx)). These include metabolites, signalling molecules and cell constituents which relate to the individual's metabolism and are induced by (patho)fysiological processes as inflammation, infection or carcinogenesis in the body. Compounds in the breath are formed in the respiratory system or originate from processes in the body and are transported to the lungs where they can be exhaled. The molecular composition of VOCs and EBC, hence, may reflect both systemic and local processes in the airways, whereas the PEx specifically reflect the composition of the lining fluid of small airways. Since volatile chemicals are recognized as sources of disease, the molecular analysis, or so called 'omics' study of exhaled air ('breathomics') emerges as a paramount instrument in monitoring health and disease in a non-invasive way. Considering the breath volatiles, there are close to 1000 reported compounds in the breath, of which little are unambiguously identified. The compounds belonged to several chemical classes, of which hydrocarbons were the most numerous chemical family. Other well-represented classes were ketones, terpenes, heterocyclic compounds and aromatic compounds. Exhaled breath volatiles and non-volatiles are explored in patients with asthma, renal and liver diseases, lung cancer, chronic obstructive pulmonary disease, inflammatory lung disease, or metabolic disorders and have been shown promising as diagnostic biomarkers. Breath tests can furthermore be used for diagnosing specific enzymes' phenotypic functionality since exhaled metabolisation products of 13C-labeled compounds gives information about the activity of metabolisation enzymes, important information in supporting personalized medicine. VOCs can also originate from exogenous exposure, such as food and drugs intake, and inhalation of chemicals (environmental, occupational 'exposome'). It is a relevant matrix to study exposure, uptake metabolism and elimination of toxic chemicals. Breath analysis, and in general the human volatolome, was first reported to investigate VOCs over forty years ago. Since that time, many methodological and technical improvements have been made. The analysis of VOCs can be done either by chemical analysis or by pattern recognition. Therefore, this project will include the following instruments to measure VOCs: Gas Chromatography-quadrupole-time-of-flight-Mass Spectrometry, sensor technology (field asymmetric ion mobility spectrometry), and selected ion flow tube-mass spectrometry. This will be combined with liquid chromatography instruments considering the analysis of non-volatiles. To analyse the high-throughput data, supervised and unsupervised data mining techniques will be used. Although the 'breath' matrix is highly interesting, there is still a great need for validation, standardization, and improved sensitivity and specificity of the process of breath collection until breath analysis. This project has the ambition to study and explore exhaled breath in its most innovative way: full molecular profiling, including characterization and quantification of volatile and non-volatile breath compounds in vivo in patients, but also ex vivo and in experimental cellular/animal models for biological translation. Therefore, this project's applications are multiple, ranging from medical/toxicological applications for non-invasive monitoring and detection of disease in humans, to research on exhalations/perspirations in the headspace of cell lines, plants, or even consumer goods. This makes the facility an attractive centre for research for several disciplines.

Keywords:LUNG FUNCTION

Disciplines:Respiratory medicine