Can you develop volatile metabolites from exhaled breath into biomarkers?

The vast number of metabolites produced by physiological processes in the body can be useful biomarkers for a variety of therapeutic applications.

Biomarkers can provide insight into important metabolic processes for health and illness, as well as potential treatment targets. A portion of the metabolites produced in the human body are volatile, known as volatile organic compounds (VOCs), and can be identified in exhaled breath.

These can spread throughout the body, entering the bloodstream and exchanging with the air in the lungs.

As a result, breath VOC analysis has been a focus of biomedical research, to translate new useful biomarkers by taking advantage of the non-invasive nature of breath samples, as well as the potential for qrepeated sampling over short periods of time.

Despite the potential of breath analysis as a new platform for metabolomic study, no VOC breath biomarkers have been successfully utilized in a clinical context as of the time of this article.

The purpose of this study is to describe the progress made in addressing the major methodological issues, such as standardization, that have historically hindered the translation of breath VOC biomarkers into the clinic.

This article discusses what efforts should be made to address these difficulties in new and ongoing breath research to enhance the successful development of VOCs in breath as a reliable source of candidate biomarkers.

The article also highlights major recent articles from specific domains, critically analyzing the progress made in the last few years to enhance breath research.

Introduction

Body fluids, such as blood, contain cells, proteins, lipids, and metabolites that can be analyzed as biomarkers to provide information on underlying physiological processes for a variety of clinical applications.

Due to their distinct features, volatile organic compounds (VOCs) found in human fluids are increasingly being investigated in the medical sector for their potential to serve as valuable biomarkers (Fig. 1).

VOCs have at least one carbon atom and are gaseous at normal temperature and standard pressure.

Endogenous VOCs from human metabolism can pass biological membranes and be emitted from bodily fluids such as breath, urine, and feces.^1,2,3

Exogenous VOCs can also enter the body through external sources such as nutrition, microbial metabolism, prescription medicines, and environmental exposure.

More than 2800 VOCs have been identified in the human body, including breath (1488), skin secretions (623), feces (443), saliva (549), urine (444), milk (290), semen (196), and blood (379).³

VOCs can be created via a variety of metabolic processes, including glucose and lipid metabolism, oxidative stress, enzyme activity, and aerobic and anaerobic fermentation by bacteria in the gut microbiome.

Lipid peroxidation has been linked to various inflammatory diseases across the body.^1,4,3 Different cell types may produce different VOC lipid peroxidation products due to their lipid compositions and redox enzyme complements.⁵

VOC detection, identification, and quantification can provide a distinct perspective on bodily processes from protein and nucleic acid studies.

Discovering the normal and pathological mechanisms that underpin the generation of VOCs may aid in the translation of new VOC biomarkers or provide innovative insights into new therapeutic methods for treating various disorders.

Figure 1. A summary of the mechanism through which VOCs originating from within the body end up in the breath, and some example disease areas that breath VOC analysis has been used for biomarker discovery. Image Credit: Owlstone Medical Ltd

Many current diagnostic procedures are limited by accessibility, patient discomfort, the need to collect multiple samples in a particular period (as with fecal sampling, urine, or blood), usability, and expense.

One of the primary advantages of using VOCs is that they may be collected noninvasively from exhaled breath.

VOC analysis could potentially meet currently unmet clinical needs to promote public health, such as early disease detection.

Breath VOC analysis has been examined as a more appealing early cancer screening technique due to its non-invasiveness, convenience of repeat sample, low overall cost, and accessibility, particularly as breath can be collected from the convenience of your own home.^6,7

This includes hydrogen and methane breath tests (HMBTs), which are accessible as at-home test kits for diagnosing specific gastrointestinal diseases. Despite the promise of exhaled breath VOC analysis, inconsistent methodology across the breath science literature have hampered the translation of VOC indicators into clinical practice.

Development of more standardized procedures involved in breath collection and analysis operations to ensure the reproducibility of VOC data has occured over recent years. This article will critically analyze the present status of the literature on the use of VOCs in exhaled breath as disease indicators in both clinical and research contexts.

The first section will describe methodological issues, such as standardization, which concerns the reliability and reproducibility of breath VOC data, as well as recent advances toward addressing and overcoming them.

Next, major publications produced since 2020 are highlighted in distinct illness scenarios and evaluated against historical literature.

Several key papers that have significantly advanced the field have been published before this time; however, these publications have already been extensively discussed in previous reviews.^8-17

As a result, this article attempts to present more recent studies while also highlighting prior publications when needed to contextualize development. This includes respiratory, infectious, gastrointestinal, and liver diseases.

Cancer is an important field where breath VOC research shows great promise and individual articles will be covered within relevant disease areas (for example, lung cancer within respiratory disease).

Finally, the use of VOC biomarkers for medication development is discussed. By outlining methodological considerations and advances in VOC breath research since 2020, the article sheds light on what future avenues must be taken to accelerate VOC biomarker development, validation, and, eventually, translation into the clinic.

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References

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About Owlstone Medical

Owlstone Medical has developed a breathalyzer for disease. With a focus on non-invasive diagnostics for cancer, inflammatory disease and infectious disease, the company aims to save 100,000 lives and $1.5B in healthcare costs.

The company’s Breath Biopsy^® platform has introduced a new diagnostic modality making it possible to discover novel non-invasive biomarkers in breath using a platform with the potential to transition to point-of-care. The award winning ReCIVA Breath Sampler ensures reliable collection of breath samples. The volatile organic compounds (VOCs) present in breath are analyzed using proven microchip chemical sensor technology (FAIMS) to detect biomarkers of disease.

The Breath Biopsy platform can be used in clinical diagnostics and precision medicine with applications in cancer and a wide range of other medical conditions. Highly sensitive and selective, these tests allow for early diagnosis when treatments are more effective and more lives can be saved.

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