Breathomics for the clinician: the use of volatile organic compounds in respiratory diseases

Abstract

Exhaled breath analysis has the potential to provide valuable insight on the status of various metabolic pathways taking place in the lungs locally and other vital organs, via systemic circulation. For years, volatile organic compounds (VOCs) have been proposed as feasible alternative diagnostic and prognostic biomarkers for different respiratory pathologies.We reviewed the currently published literature on the discovery of exhaled breath VOCs and their utilisation in various respiratory diseasesKey barriers in the development of clinical breath tests include the lack of unified consensus for breath collection and analysis and the complexity of understanding the relationship between the exhaled VOCs and the underlying metabolic pathways. We present a comprehensive overview, in light of published literature and our experience from coordinating a national breathomics centre, of the progress made to date and some of the key challenges in the field and ways to overcome them. We particularly focus on the relevance of breathomics to clinicians and the valuable insights it adds to diagnostics and disease monitoring.Breathomics holds great promise and our findings merit further large-scale multicentre diagnostic studies using standardised protocols to help position this novel technology at the centre of respiratory disease diagnostics.

Keywords: exhaled airway markers; respiratory infection.

Figure 1

This figure highlights the complex kinetic of gaseous exchange. Endogenous VOCs can originate from the lungs or distant organs, via systemic circulation. Exogenous VOCs are continuously introduced into the respiratory system which can result in the production of volatile downstream products. Breath samples containing endogenous and exogenous VOCs are analysed to generate clinically meaningful data.

Figure 2

Exhaled breath VOCs can be analysed using offline or online technologies. Offline technologies, currently considered gold standard, involve storing samples in a sorbent tube or collection bag prior to injecting them to an analytical instrument (e.g. GC-MS). Online technologies involve direct introduction of breath samples to analytical instruments for analysis, negating the need for sample collection and storage. Online technologies require less analytical instrument time and technical skills and results can be obtained immediately, however, they lack the ability to identify compounds with high fidelity which limited its applications