Inflammation is a broad biological response that stimulates defense, healing, and repair in response to injury or disease. This involves a complex network of responses involving various biological pathways and cell types throughout the body, particularly within the immune system.

Therefore, it is not surprising to note that several biomarker studies consider inflammation as a potential source of biomarkers (see, for example, a recent review of respiratory diseases by Ibrahim et al.).¹). But how useful and relevant are inflammatory biomarkers in disease diagnosis?

A variety of factors can cause inflammation, including injury, infection, and irritation. The main symptoms of an inflammatory response include heat, swelling, redness, and pain. In general, inflammation is classified into two forms: acute and chronic.

Acute inflammation usually lasts for hours or days and is regulated primarily by neutrophils, whereas chronic inflammation can last for years and involves mononuclear cells. Long-term chronic inflammation becomes more common as we age, and while it can negatively impact overall health, it can also be a factor in cancer progression.

Inflammation is expected to produce exhaled breath biomarkers

For several inflammatory diseases, current diagnostic methods are expensive and invasive. This can cause additional stress to the patient. Therefore, non-invasive alternatives are very attractive. Inflammation is a hallmark of many diseases studied in exhaled breath research (Figure 1).

Inflammation is associated with chronic respiratory diseases, liver disease, cancer, infections, and gastrointestinal diseases. Several inflammatory processes result in the production and release of small molecules that can directly or indirectly result in volatile organic compounds (VOCs) that can be detected in exhaled breath.

As a result, breath biomarkers may provide a way to perform cheaper, faster, non-invasive screening procedures to aid in the diagnosis and monitoring of inflammatory diseases.

A selection of inflammatory diseases that have been studied through respiratory research.

Figure 1. A selection of inflammatory diseases that have been studied through respiratory research. Image credit: Owlstone Medical Ltd

Inflammation is associated with responses to hypoxia and processes such as oxidative stress/lipid peroxidation, pathogen metabolism, and degradation. Some of these conditions were previously investigated in Owlstone’s series on lipid peroxidation and the Warburg effect. It should be noted that activated immune cells use systems related to oxidative stress as a weapon to attack pathogens and destroy damaged cells.

Damaged and dying cells are frequently found at sites of inflammation, and these cells may also release distinct macromolecules and metabolites, such as protein and lipid breakdown products. Therefore, inflammation may include a wide range of potential biomarkers.

Figure 2. Unsaturated fatty acids are converted into a complex range of pro- and anti-inflammatory compounds through different metabolic processes, indicating a complex relationship between metabolism and the regulation of inflammation. Image credit: Adapted from Maskrey et al.²

Biomarkers of inflammation may be specific

Although inflammation is a common bodily response associated with many injuries and diseases, there is good reason to believe that inflammation-related biomarkers are relevant to the diagnosis and treatment of certain diseases.

There is a significant amount of redundancy in inflammation, with many triggers that can be detected and monitored by different parallel and complementary signaling systems (Figure 3), protein complexes, cell types, etc. All of these come together to achieve similar results. The main features of inflammation.

This implies that there are some important differences between seemingly similar inflammatory responses, leading us to believe that biomarkers of inflammation may differ from disease to disease and even between disease phenotypes. There’s an important reason.

This is a demonstrable fact in asthma, where different inflammatory endotypes given the presence of different immune cells generate different disease phenotypes that require different treatment regimens. The different phenotypes of asthma are the result of parallel inflammatory pathways. This diagram helps illustrate just a portion of the complexity of inflammation and how this requires different treatments for different types of asthma, such as inhaled corticosteroids (ICS).

Figure 3. The different phenotypes of asthma are the result of parallel inflammatory pathways. This diagram shows just a small part of the complexity of inflammation and how it causes different types of asthma and requires different treatments, such as inhaled corticosteroids (ICS).Image credit: Adapted from Durham et al.³

Inflammation can also produce bodily byproducts that are highly context-dependent (Figure 4). In processes such as lipid peroxidation, interactions between reactive oxygen species and fatty acids in cell membranes release small molecules.

Because the composition of these membranes differs between cell types and between organelles, it is plausible that there may be a correlation between where lipid peroxidation occurs and the mixed mixture of small molecules produced. It’s reasonable.

Examples are provided of how different inflammatory processes and resulting small molecule biomarkers are associated with different diseases in disease-specific ways.

Figure 4. Examples are provided of how different inflammatory processes and resulting small molecule biomarkers are associated with different diseases in disease-specific ways. Image credit: Owlstone Medical Ltd

Inflammation-related biomarkers are unlikely to be used alone to make a final diagnosis of the disease. Even if inflammation always releases biomarkers of the same composition, this only provides part of a broader diagnostic picture. Therefore, these biomarkers may be evaluated in parallel with other biomarkers to provide more specific results in studies.

The ability to identify groups of biomarkers for disease detection depends on the application of reliable biomarker detection tools such as exhaled breath biopsies.^® OMNI is optimized for a wide range of sensitive biomarker discovery.

There’s still more to discover

Inflammation represents a promising source of rich and diverse metabolic biomarkers that can influence VOCs in exhaled breath. Several studies have revealed an association between exhaled breath biomarkers and inflammation, and it is reasonable to assume that there may be several others.

Although further research is still needed into the mechanistic relationship between biomarkers and biology, the prevalence of inflammation in the development of injury and disease is clear, and in the future, clinical biomarkers will report inflammatory processes. There is a possibility. Breath biopsy is a non-invasive and reliable method to identify and study biomarkers in exhaled breath.

References and further reading

1. Ibrahim, W., et al., A systematic review of the diagnostic accuracy of volatile organic compounds and their relationship with type 2 inflammatory markers in airway diseases. ERJ Open Research, 2021. 7(3): 00030-2021. DOI: 10.1183/23120541.00030-2021
2. Maskrey, BH et al. Mechanisms of inflammation resolution: Focus on cardiovascular disease. Arteriosclerosis Thrombus Vasc Biol, 2011. 31(5): p. 1001-6. DOI: 10.1161/ATVBAHA.110.213850
3. Durham, AL, et al. Targeted anti-inflammatory therapy in asthma and chronic obstructive pulmonary disease. translational research, 2016. 167(1): p. 192-203. DOI: 10.1016/j.trsl.2015.08.004
4. Ratiu, IA et al. Volatile organic compounds in exhaled breath as fingerprints of lung cancer, asthma, and COPD. clinical medicine journal2021. 10(1): p. 32. DOI: 10.3390%2Fjcm10010032
5. Kurada, S., et al., Review article: Breath analysis in inflammatory bowel disease. Digestive pharmacology and therapeutics, 2015. 41(4): p. 329-41. DOI: 10.1111/apt.13050
6. Ahmed, I., et al. Investigation of fecal volatile organic metabolites as novel diagnostic biomarkers in inflammatory bowel disease. Digestive pharmacology and therapeutics, 2016. 43(5): p. 596-611. DOI: 10.1111/apt.13522
7. Risby, TH and SS Sehnert, Clinical applications of exhaled breath biomarkers of oxidative stress status. Free radical biology and medicine, 1999.27(11): p. 1182-1192. DOI: 10.1016/s0891-5849(99)00212-9
8. Ligor, T. et al. Search for potential markers of glomerulopathy in urine by HS-SPME-GC×GC TOFMS. molecule2021. 26(7): p. 1817.DOI: 10.3390%2F molecule 26071817
9. Monedeiro, F. et al. VOC profile of saliva in the evaluation of halitosis and submandibular abscess using HS-SPME-GC/MS technology..molecule2019. 24(16): p. 2977.DOI: 10.3390%2F molecule 24162977
10. Phillips, M., et al. Prediction of heart transplant rejection by breath testing for markers of oxidative stress. Am J Cardiol, 2004. 94(12): p. 1593-4. DOI: 10.1016/j.amjcard.2004.08.052

About Owlstone Medical Co., Ltd.

Owlstone Medical develops breathalyzers focused on non-invasive diagnosis of cancer, inflammatory and infectious diseases, and aims to save 100,000 lives and $1.5 billion in healthcare costs. Masu.

The company’s breath biopsy^® The platform has introduced a new diagnostic modality that enables the discovery of novel non-invasive biomarkers in exhaled breath with a platform that has the potential to move to the point of care. The award-winning ReCIVA breath sampler ensures reliable breath sample collection.

Breath Biopsy has applications in cancer and a wide range of other medical conditions to support early detection and precision medicine research. These tests are sensitive and selective, allowing for early diagnosis when treatment is more effective and more lives can be saved.

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