Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions.

Exhaled air contains many volatile organic compounds (VOCs) that are the result of normal and disease-associated metabolic processes anywhere in the body. Different omics techniques can assess the pattern of these VOCs. One such omics technique suitable for breath analysis is represented by electronic noses (eNoses), providing fingerprints of the exhaled VOCs, called breathprints. Breathprints have been shown to be altered in different disease states, including in asthma and COPD. This review describes the current status on clinical validation and application of breath analysis by electronic noses in the diagnosis and monitoring of chronic airways diseases. Furthermore, important methodological issues including breath sampling, modulating factors and incompatibility between eNoses are raised and discussed. Next steps towards clinical application of electronic noses are provided, including further validation in suspected disease, assessment of the influence of different comorbidities, the value in longitudinal monitoring of patients with asthma and COPD and the possibility to predict treatment responses. Eventually, a Breath Cloud may be constructed, a large database containing disease-specific breathprints. When collaborative efforts are put into optimization of this technique, it can provide a rapid and non-invasive first line diagnostic test.