In this track, the Zurich Exhalomics consortium will continuously develop new biomarkers for respiratory diseases by analyzing and comparing the exhalome of patients with healthy individuals. The University Hospital Zurich and the University Children's Hospital Zurich have access to a big number of patients that are involved in over ten clinical trials today already.
Early diagnosis and prevention of asthma in children
Alexander Möller (Kispi), Renato Zenobi (ETH), Pablo Martinez-Lozano Sinues (UniBasel/UKBB) and Malcolm Kohler (UZH/USZ)
Around 300 million people worldwide are affected by asthma. It is the most common chronic disease occurring during childhood. There is no cure for asthma, only symptoms can be alleviated or prevented by avoiding triggers, such as irritants, and by drugs, e.g. inhaled corticosteroids. In Switzerland, every third child experiences wheezing attacks associated with breathing difficulties during preschool age. While most of the children grow out their wheezy illness until school age, around one third of these children will suffer from asthma. As to date, proper diagnosis of asthma in preschool age is still nearly impossible; many young children are not adequately treated. By applying on-line, real-time ambient ionization mass spectrometry, we aim to investigate specific biomarkers in breath to allow early diagnosis of asthma and thereby prevent asthma attacks in preschool children by timely initiation of an effective treatment. The possibility to predict and diagnose asthma in young children would have a huge impact by reducing the extensive health care costs and physical and psychological burden for the affected children and their families.
Early non-invasive detection of lung disease and infection in children with cystic fibrosis
Alexander Möller (Kispi), Renato Zenobi (ETH), Pablo Martinez Lozano-Sinues (UniBasel/UKBB) and Malcolm Kohler (UZH/USZ)
Cystic fibrosis (CF) is a genetic disease that affects mostly the lungs but also the pancreas, liver, kidneys and intestine. From birth, patients suffer from chronic pulmonary infection and inflammation leading to irreversible lung destruction and premature death. There is no cure for CF. In the European Union, one in 2000 to 3000 newborns is affected by CF.
The early detection of disease and disease-associated complications is crucial for implementing timely therapeutic and preventive measures to reduce disease burden and improve prognosis. We aim to identify and validate specific metabolites in the breath of children with CF to reliably and non-invasively diagnose both early infection and inflammation processes in the lungs by using Secondary Electrospray Ionisation Mass Spectrometry (SESI-MS). Further we aim to develop sensitive and specific non-invasive tools for diagnosis and monitoring that are applicable bedside in large numbers of children.
Diagnosis of bacterial pneumonia
Pablo Martinez-Lozano Sinues (UniBasel/UKBB), Annelies Zinkernagel (UZH/USZ), Renato Zenobi (ETH) and Malcolm Kohler (UZH/USZ)
Pneumonia is the leading infectious cause of death worldwide, mainly among children. For example, pneumonia accounts for 15% of all deaths of children less than 5 years of age (an estimated 935,000 children each year). Globally, pneumonia affects approximately 450 million people and results in about 4 million deaths per year. Hence, it exacts an enormous cost in economic and human terms. Early diagnosis is crucial for treatment success and improvement of outcome. However, the high morbidity and mortality of pneumonia is partly due to the lack of efficient diagnostics.
Our ultimate objective will be diagnosing bacterial pneumonia using a non-invasive breath test, that will deliver a positive/negative response and will identify a subset of causing pathogens in ~15 min. The figure describes the clinical problem and the proposed solution.
Circadian and sleep-related metabolic changes detected in breath - new clues to disease in a 24-hour society
Steven A. Brown (UZH), Pablo Martinez-Lozano Sinues (UniBasel/UKBB), Renato Zenobi (ETH) and Malcolm Kohler (UZH/USZ)
Metabolism is profoundly affected by both a "circadian clock" directing daily physiology throughout the body, and a “sleep homeostat” directing quiescence and wake. Recent evidence from mice and humans suggests that disturbance of either of these axes causes metabolic disease. Breath metabolomics is a new and non-invasive way to understand these changes and could provide potent biomarkers for impending disease. Using this revolutionary technology, we will define the normal changes in metabolism that occur daily during sleep and waking, and how these are altered in patients with asthma and sleep apnoea.
Fat burn monitoring
Sotiris Pratsinis (ETH), Andreas Güntner (ETH) and Malcolm Kohler (UZH/USZ)
Obesity is a global health threat on the rise and its prevalence continues to grow. Worldwide more than 15% of women and 11% of men are obese (BMI ≥ 30 kg m-2) with increasing numbers in most countries. Unfortunately, suitable technologies to monitor the body fat burn rates in situ to guide physical activity or dietary interventions toward efficient weight loss are missing. Analyzing volatile compounds in human breath opens exciting new avenues for the next generation of health monitoring devices. Here, portable breath detectors will be developed that enable easily applicable and hand-held body fat burn monitoring for personalized and immediate feed-back on workout and dieting effectiveness. First results were obtained with a breath acetone sensor that followed well individual fat burn rates during exercise and rest in 20 volunteers.
Exhaled breath analysis in pediatric patients exposed to environmental tobacco smoke
Pablo Martinez-Lozano Sinues (UniBasel/UKBB), Joachim Buhmann (ETH)
Exposure of children to environmental tobacco smoke (ETS) can lead to serious health consequences, impairing lung development, and increasing the risk for respiratory disease in adulthood. While there is strong evidence confirming detrimental effects of ETS from clinical observational studies, much remains unknown at the molecular level which could improve our understanding of the mechanisms by which ETS affects respiratory health. ETS has been associated with alterations in cell signaling, ultimately causing impaired cellular growth in lung tissue. The objective of this project is to identify exhaled markers altered as a result of ETS exposure, thus gaining insights on the detrimental effects of ETS. We will measure cotinine levels using standard analytical methods to objectively assess the level of exposure on an individual basis. We will seek associations between systemic cotinine concentrations and exhaled metabolite levels. Obtaining evidence of the detrimental effect of ETS exposure in the respiratory system as assessed by exhaled metabolites will provide a valuable input to public health policymakers.