Breath VOC biomarkers for infectious diseases

Breath analysis relies on the idea that the volatile organic compound (VOC) profile of exhaled breath is altered as a response to underlying pathological states and that these VOCs can be detected and measured to be used for disease diagnosis and monitoring. Exhaled VOCs reflect not only the metabolic processes occurring in the respiratory tract but also metabolic activity occurring in distal parts of the body. This is because circulating VOCs in the blood may diffuse into the alveolar space for exhalation.

The non-invasive nature of breath analysis makes it attractive for disease diagnosis and monitoring as repeat measurements can be taken with minimal discomfort to the participating patients. VOCs in breath can originate from the environment, endogenous host metabolism, and the metabolic activity of microbes in the body, including pathogens and the microbiome in the gut and airways. Endogenous VOCs have the potential to provide a window into the physiological state of an individual, and microbial VOCs could assist in the identification of pathogens.

An infectious disease can be defined as an illness due to a pathogen or its toxic product, which arises through transmission from an infected person, infected animal, or contaminated object to a host. Infectious diseases are responsible for a huge global burden of disease that impacts public health systems and economies worldwide, especially affecting vulnerable populations. Lower respiratory tract infections, diarrheal diseases, malaria, and tuberculosis (TB) are among the top causes of overall global mortality (1).

Research has indicated that VOCs in breath are associated with infectious diseases, showing promise as non-invasive biomarkers. Pathogenic microbes can alter the VOCs in breath either through altered metabolic pathways in the host such as the immune response, inflammation to the affected tissues, or with certain pathogens like bacteria and fungi, their own endogenous metabolic processes.

Some infectious diseases predominantly affect the lungs and other tissues in the respiratory tract such as the nose and throat, and as breath is in direct contact with these tissues, breath analysis can provide a direct insight into the disease as opposed to other more indirect sampling mediums such as blood or urine. We completed a literature review to summarize VOC biomarkers for infectious diseases, Table 1 highlights our findings.

Table 1 – a table summarizing VOCs found to be associated with multiple different infectious diseases.

VOCs in breath are associated with infectious disease

This table presents a comprehensive summary of VOCs associated with various infectious diseases, offering insights into potential biomarkers for diagnosis and monitoring. Diseases covered include aspergillosis, C. diff infection, COVID-19, cystic fibrosis, influenza, malaria, pneumonia, sepsis, and tuberculosis. The compounds identified by these studies require further investigation to discover the disease-related pathophysiology that leads to their changing abundance in the breath.

Out of the 56 compounds identified in this literature search, 25 of them were contained within our Breath Biopsy® VOC Atlas. Our VOC Atlas contains VOCs that have been carefully quantified for their presence in the breath (‘on-breath’) of a population of heterogeneous volunteers without any specific pathophysiology, and all VOCs have undergone rigorous validation to confirm their identities. There are two groups of compounds included in the Atlas – ‘on-breath’ and ‘off-breath’. On-breath compounds are thought to be associated with normal variation in the population, whereas off-breath compounds in the VOC Atlas are compounds that are not regularly observed in healthy individuals.

This means that off-breath compounds may only be detectable in the breath of those with disease and not in the breath of a healthy person, and therefore are promising to investigate further as potential breath biomarkers of disease. In this literature search, there were a total of 9 on-breath compounds and 16 off-breath compounds. Aldehydes such as octanal and heptanal (found in the breath of COVID-19 patients) are off-breath compounds that can be formed endogenously by lipid peroxidation, which could suggest that lipid peroxidation may be a source of the altered VOC signature seen in the breath of patients with infectious diseases.

Inflammation of the airways is a common characteristic of many infectious diseases, generating oxidative stress in the tissues of the respiratory tract. Oxidative stress causes the release of compounds, including alkanes. Decane (found in the breath of tuberculosis patients), heptane (found in the breath of pneumonia patients), and pentane (found in the breath of cystic fibrosis patients) are examples of off-breath alkanes found in this literature search that could be due to oxidative stress. However, it is important to note that whilst off-breath compounds do have the potential of being off-breath in a healthy population and on-breath in disease (making them ideal biomarkers), there is also clinical potential in on-breath compounds that are significantly increased/decreased in disease.

To progress these biomarkers towards validation, and eventually translation into further breath tests for infectious disease in clinical use, more work needs to be done to link the characteristic changing levels of these compounds in the breath in infectious disease, and the underlying mechanisms responsible. We can incorporate the use of breath analysis into your infectious disease research as part of our Breath Biopsy OMNI® service to enhance and fast-track breath biomarker identification and validation. To find out more information about breath biomarkers for infectious disease, and other potential research studies involving the use of VOCs, please do not hesitate to contact us.

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