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.