Malignant pleural mesothelioma (MPM) is a rare but very lethal tumour of the serous membranes of the lungs with a
dismal prognosis and is linked to exposure to asbestos fibres (1, 2). Treatment strategies for MPM include radiation
therapy, chemotherapy, surgery and a combination of these methods. There are several chemotherapy treatment
regiments available including single-arm and combination regimes and. more recently, targeted therapies have
become available (1). Currently, CT-scans are used to monitor treatment response. However, this lacks accuracy. is
expensive and is potentially harmful. The lack of a simple and effective tool for predicting therapeutic efficacy and
prognosticating the disease has hampered the progress in deVising strategies to improve survival of these patients.
Belgium is a historical champion of asbestos consumption and the incidence of mesothelioma in asbestos-exposed
populations will continue to rise in the next decades (3, 4) urging the need for early detection 10015, since diagnosis is
delayed by non-specific, late symptoms and imaging difficulties jeopardizing the efficient management.
The quest for a simple. non-invasive diagnostic test recently shifted to exhaled breath. Therefore, this study focuses
on innovation through exhalation. Exhaled breath provides a revealing source of markers present in picomolar
concentrations which can be obtained cheaply, non-invasively. and completely safe: Volatile Organic Compounds
(VOCs). Already, there are over 3000 different VOCs (pentane, acetone, aldehydes ... ) detected in human breath (5).
VOCS can originate from exogenous sources like ambient air but also, more importantly, from endogenous
biochemical processes (via disease-specific mechanisms and enzyme reactions) and enter the lung alveoli by gas
exchange mechanisms (6). It is knolMl that OXidative stress and polymorphism in CYP450 enzymes are linked to
cancer and both affect the abundance of VOCs in the breath (6). Since the first Identification of VOCs in 1971 (7), the
field of breath analysis skyrocketed into a high-throughput breathomics field (8), focusing on sampling methods and
statistical procedures to take breath analysis to the clinic.
Despite that current guidelines dissuade MPM screening (9), a lot of wild screening occurs in the community at an
unknOIMl cost: asbestos-exposed individuals are subjected to non-specific investigations for diagnosing MPM (lung
function testing, CT-scans or X-rays). Nevertheless, the only way to diagnose MPM with complete certainty is through
pathological examination of a biopsy obtained in most instances via an invasive thoracoscopy (1). A non-invasive and
simple test which makes detection of MPM at an early stage possible could reduce the economic burden of wild
screening and improve the management of MPM. Since asbestos is known to induce oxidative stress at the
mesothelium and cancers upreguiate their metabolism, we believe that the VOCs, and hence, the breath composition
differs between MPM patients and controls and therefore, we initiated the MesoBreath Study. Exhaled breath of MPM
patients was assessed in a multicentre, cross-sectional study and compared to the breath of healthy asbestosexposed
and non-exposed controls, patients with benign asbestos-related diseases and benign non-asbestos-related
pulmonary diseases and lung cancer patients. Breath samples were analysed with multicapillary column-ion mobility
spectroscopy (MCCIIMS) and extra breath samples were taken for validation and VaC-identification with Gas
Chromatography - Mass Spectrometry (GG-MS) and electronic nose (eNose) sensor analysis.