Biomedical engineering for breathomics: towards clinical application in respiratory diseases Biomarkers, instruments and technology readiness levels

Rising number of patients affected by asthma, COPD or lung cancer in most parts of the world, combined with the emerging systems medicine concept and the increasing availability of biological therapies for respiratory diseases, call for further improvement in diagnosis and management of disease. In particular this holds for better phenotyping of individual patients, which is a prerequisite for the development and optimization of precision medicine approaches. This calls for new (non-invasive) biomarkers for early detection, biological phenotyping, monitoring of disease activity, selection of therapies, individualized dosing of therapies and prediction of outcome. Exhaled breath contains thousands of volatile organic compounds (VOCs) that are reflective of metabolic processes in the body. Comprehensive analysis of expired VOCs (breathomics) includes many favouring aspects that fit the unmet need of (non-invasive, point-of-care) tools for the detection of biomarkers. The aim of this thesis was to develop breathomics (by electronic nose technology) further towards a point-of-care tool in (chronic) respiratory diseases. Studied areas of application were: diagnosis, phenotyping, therapeutic drug level measurement, screening and disease activity monitoring. From an engineering perspective there were advancements on sampling and analyses strategies to support (international) multicentre research. Furthermore, the foundation of SpiroNose, a concept which merges breathomics with well-established spirometry, has enabled to run breathomics research in busy outpatient settings. eNose technology is heading towards clinical application step by step, however there are important challenges as it concerns metabolic evidence, confirmation of findings and dealing with confounders like drug usage and smoking.