Volatile Organic Compounds (VOCs), A Potential Biomarker To Human Disease And Tumors.
Laboratory Tests

Author: hussam maree
Date: 07/07/2014


Hundreds of volatile organic compounds (VOCs) are emitted from the human body, and the components of VOCs usually reflect the metabolic condition of an individual.
Therefore, contracting an infectious or metabolic disease often results in a change in body odour.
Recent progresses in analytical techniques allow rapid analyses of VOCs derived from breath, blood, skin and urine. Disease-specific VOCs can be used as diagnostic olfactory biomarkers of infectious diseases, metabolic diseases, genetic disorders and other kinds of diseases such as cancer.
Understanding the pathophysiological mechanisms underlying The production of disease-specific VOCs may provide an insights into therapeutic approaches for treatments for various diseases.
Further understanding and research on chemical and clinical aspects
of body-derived VOCs, may provide on the near future, interesting and surprisingly new NON INVASIVE diagnostic potential which is the olfactory diagnosis.

Pathological processes, such as infection and endogenous metabolic disorders, can influence our daily odour fingerprints by producing new VOCs or by changing the ratio of VOCs that are produced normally. Therefore, it is not surprising that physicians have used their olfactory senses to diagnose physical conditions of patients. Many years past, Hippocrates recognized the diagnostic usefulness of body odours and reported on several disease-specific odours emanated from urine or sputum. Despite the potential clinical usefulness of VOCs and body odours, little work has been done to define these compounds as diagnostic criteria, either qualitatively or quantitatively.

the diagnostic potential in breath analysis.
Analytical determination and detection of individual odor signatures.

How VOCs are detected:
During the second-half of the 20th century, gas chromatography (GC)and gas chromatography and mass spectrometry (GC-MS) have been used to separate and indentify VOCs. In the 1990s, a GC-MS-olfactometer (GC-MS-O) was developed,and it has enabled researchers to examine mass spectra and odour qualities of individual GC-separated odourants simultaneously.Using the GC-MS-O, researchers can identify characteristic odorous compounds that are in low abundance in a complex mixture of VOCs from various biological samples. These sophisticated analytical techniques have allowed studies to focus on searching for VOCs that represent specific odours from patients. The identified compounds may then have potential as biomarkers that could be useful for diagnosing diseases.

The origins of body odour:
Body odours are a result of the combination of hundreds of emitted odorous VOCs that are originally secreted from various cells inside the body via metabolic pathways. The major sources of VOCs include breath, sweat, skin, urine, faeces and vaginal secretions. Blood is also an important source of body odours because some metabolically produced VOCs are secreted into blood and eventually emitted to the external environment via breath and/or sweat.

BREATH: Collecting breath samples is extremely simple, painless and non-invasive. Consequently, many GC-MS analyses of breath samples have been performed, and in some cases, researchers and clinicians have succeeded in identifying VOCs that are specific to certain diseases.
Trimethylamine was found in the breath of patients with trimethylaminuria;
Acetone was found in the breath of patients with diabetes;
Methylmercaptan was found in thebreath of patients with fetor hepaticus

Skin&sweat glands:VOCs derivied from s.glands,sebum and risedent bacteria.Any alteration in homeostatic balance due, for instance, to some inherited metabolic disorder or bacterial infection of the diseased area can induce changes in both the quality and quantity of VOCs.
some infectious diseases or cancerous wounds develop characteristic, offensive odours. Samples are easily obtained by collecting VOCs emitted from the affected area directly onto an absorbent solid-phase microextraction (SPME) fibre

Urine: The substances in urine are intermediate products or end products of a number of metabolic pathways, and these substances contain a variety of structural motifs, such as ketone, alcohol, furan, pyrrole and sulphide, which often cause a particular odour.

Blood: According to Horvath et al(*), trained dogs can discriminate between blood samples from ovarian cancer patients and blood samples taken from patients with other gynaecological cancers or from healthy control subjects. This study suggests that specific odour(s) in the blood may be useful for screening and diagnosing different disorders such as lung cancer and hepatic encephalopathy (**).
Further studies are needed to evaluate these results and to apply these findings to clinical diagnoses.

* Characteristic odour in the blood reveals ovarian carcinoma.
** A gas chromatographic--mass spectrometric study of profiles of volatile metabolites in hepatic encephalopathy..
Investigation of volatile biomarkers in lung cancer blood using solid-phase microextraction and capillary gas chromatography-mass spectrometry..

Pathology related odors:
1-)Infectious diseases;
Microbial species produce various kinds of volatile compounds in the host body,due to intercation with organic components, and these volatiles are liberated in breath, urine, faeces
and sweat. Using GC analysis of volatiles of cultures, it has been shown that microorganisms
produce various odorous compounds such as alcohols, aliphatic acids and terpenes, and that the ratio of these compounds differs depending on the infectious microorganism.

2-)Inherited disorders of metabolism:
Metabolic disorders may derive from enzyme deficiencies or other defects often result in the accumulation of particular metabolites , due to impairment in normal biochemical pathways. Thus,normaly these disorders are usually diagnosed by the detection of increased concentrations of these metabolites.
However some of these disorders are associated with a characteristic odour due to
the accumulation of certain odorous metabolites in the body, and these odours are sometimes
distinctive enough to be diagnosed by clinicians.

Phenylketonuria ;(PKU) is an inherited autosomal recessive disorder characterized by hyperphenylalaninemia resulting from deficiency of hepatic phenylalanine hydroxylase (PAH), which converts phenylalanine into tyrosine., which is abnormally metabolized to phenylacetate, Phenylacetate in sweat and urine of the patients appears to be the cause of a musty odour.

Maple syrup urine disease: Maple syrup urine disease is a defect in the metabolism of the branched-chain amino acids (BCAAs), valine, leucine and isoleucine.
This disease leads to mental retardation and cerebral degeneration, and is caused by the deficiency of an enzyme that catalyses BCAAs,as a risult BCAAs and their corresponding reduced products accumulate in tissues and body fluids,and manifests as a sugar like odour that is evident during the first week after birth,

Profiles of urinary volatiles from metabolic disorders characterized by unusual odors..
The discovery of phenylketonuria: the story of a young couple, two retarded children, and a scientist..

3)metabolic diseases;
Diabetes/diabetic ketoacidosis; In patients with type 1 diabetes cannot synthesize Insulin, glucose accumulates in the blood, and is excreted in the urine. Under these conditions, cells use fatty acids rather than glucose as an energy source.
However, fatty acid catabolism creates ketone compounds, such as acetoacetate, 3-hydroxybutyrate and acetone,witch causes acidity of the blood, These excess ketones are secreted in the urine and breath. As a result, the patient’s urine and breath have a fruity odour due to the presence of acetone.

Uremia;in patients with Kidney failure the presence of excessive nitrogenous
waste products, such as urea, in the blood stream produces an ammonia or urine-like odour in breath, which is caused by the breakdown of urea to ammonia and trimethylamine in the saliva.

Scurvy: Scurvy is a disease caused by vitamin C deficiency, which is required for the synthesis of collagen. Scurvy patients produce sweat with a putrid odour.


Human exhaled air analytics: biomarkers of diseases..

Based on GC-MS analyses, some VOCs were recently identified as candidate cancer-specific substances in breath, urine, tissue and/or blood samples from cancer patients.
For example, breath samples from breast cancer patients have been examined. Hydrocarbons, such as alkanes and monomethylated alkanes, were originally
identified as markers for oxidative stress, and a unique combination of these hydrocarbon VOCs was found in breath samples from breast cancer patients.
Breath samples from lung cancer patients were also Examined, and recent studies indicates that some VOCs emitted from cultured lung cancer cells(cancer cell membrane) were the same as those in breath samples of lung cancer patients .These findings show the existence of lung cancer-specific VOCs and VOC biomarkers will become effective tools in cancer screening.

Dogs can be used as cancer detectors because they have an extraordinary sense of smell;
In cases of melanoma, bladder cancer, ovarian cancer and colorectal cancer, dogs can be trained to distinguish patients based on VOCs from patients’ urine, tumors or breath samples, more successfully than would be expected by chance alone.

Recently, the application of an electronic nose is also recommended. For example,
melanomas have reportedly been identified by measuring VOCs from the lesions using a chemical sensor array.

Biomarkers in cancer staging, prognosis and treatment selection.
Volatile markers of breast cancer in the breath.
Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study..

Progresses in analytical methods such as GC, GC-MS and GC-MS-O have provided an opportunity to identify VOCs related to diseases in research laboratories.
At present, it is necessary however to improve the accuracy of the sensors and their sensitivity to marker VOCs. Once these improvements are made, disease-specific ‘volatile biomarkers’ will be used more regularly in clinical practice.
Finally, it should be pointed out, that VOCs information is helpful in understanding the cause of disorders, thus therapeutic targets for some infectious or metabolic diseases could be identified.

2014-07-07T15:51:01 - hussam maree
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