The role of respiratory analysis in the diagnosis of diseases

Breath key metabolites
Common techniques associated with breath analysis
Collection and analysis of stored breath samples
Diagnosis of disease using volatile biomarkers
Commercial production of breath analyzers for disease detection
References
Further reading


Breathing is an important matrix for the analysis of volatile organic compounds (VOCs) that are generated in the body. These compounds travel through the blood in the body, reach the alveolar interface and are eventually exhaled. Exhaled breath testing for VOCs could indicate whether an individual is sick or healthy.

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Researchers have documented evidence for the presence of detectable VOCs in the breath linked to breast and lung cancer. The scientific community has shown great interest in identifying all the parameters influencing the presence of VOCs in exhaled air. In this context, he focused on the standardization of breath sampling and analysis methodology. Breath analysis can lead to rapid and non-invasive detection of various diseases, such as diabetes and cancer.

Breath key metabolites

Typically, exhaled breath consists of unmodified nitrogen (~74%), argon (~1%), oxygen (~15%), carbon dioxide (~5%), and water vapor (~6%). Additionally, several endogenously formed gaseous volatile metabolites are present in exhaled breath at trace levels, which are measured in parts per million volume (ppmv), parts per trillion volume (pptv), or parts per billion volume. volume (ppbv).

The researchers detected common respiratory metabolites in several healthy individuals for thirty days, such as acetone, methanol, ammonia, acetaldehyde, propanol, isoprene and ethanol. These metabolites were detected by the selected ion flow tube mass spectrometry (SIFT-MS) method. The variability of the concentrations of these metabolites was evaluated and the log-normal distribution of these metabolites was studied.

Ammonia is present in the body as a breakdown product of proteins via bacterial breakdown in the gut. Although a large part of the ammonia is converted into urea and eliminated through urine, a small part is expelled through the breath. The concentration of ethanol and methanol may increase due to anaerobic fermentation by intestinal bacteria. The presence of isoprene in human breath has been considered a marker of cholesterol synthesis. Additionally, scientists have revealed that an abnormal level of isoprene in human breath indicates end-stage renal disease and oxidative stress.

Common techniques associated with breath analysis

Two of the analytical tools used to analyze breath to detect and quantify trace gases in real time with high sensitivity are Proton Transfer Reaction Mass Spectrometry (PTR-MS) and SIFT-MS. Both PTR-MS and SIFT-MS are known as soft ionization techniques capable of detecting biomarkers present in breath samples, ranging from ppbv to pptv. Although SIFT-MS is less sensitive than PTR-MS, it is advantageous because it does not use an electric field and the reactions occur under thermal conditions.

The researchers also used ion mobility spectrometry (IMS) and laser absorption spectroscopy (LAS) in breath analysis. Cavity Reduction Spectroscopy (CRDS), based on LAS, was used to measure nitrous oxide (NO) in expired air. This technique can quantify VOCs in the breath below parts per billion by volume levels.

Electron Noses (e-Noses) is an electronic sensing device that contains an array of gas and semiconductor-based sensors. Two devices based on mass-sensitive sensors, namely quartz crystal microbalance (QCM) and surface acoustic wave (SAW), are used in breath analysis.

Collection and analysis of stored breath samples

Direct sampling is preferred for breath analysis because it limits the possibility of loss of compounds through diffusion or sample degradation. However, in the scenario where direct sampling is not possible, an appropriate exhaled breath storage system is an important aspect. Scientists indicated the risk of contamination of breath samples with background emission of pollutants, which could alter the chemistry of stored samples.

At present, inert Tedlar bags with many advancements are manufactured by many companies, such as Dupont and SKC Ltd. These bags are transparent or black and are based on various components, such as Nalophan, Flexfoil and Teflon. Previous studies have indicated that Nalophan bags are inexpensive and the most popular for collecting breath samples. The stability of the respiratory components in the Tedlar bags was determined by gas chromatography-MS (GC-MS) and PTR-MS.

Stored breath was analyzed for the presence of VOCs via various methods such as needle trap micro-extraction (NTME) combined with GC and solid-phase micro-extraction (SPME).

Diagnosis of disease using volatile biomarkers

Scientists evaluated SIFT-MS and PTR-MS technologies to determine if they can detect liver disease and monitor diabetes. Moreover, these techniques have also been evaluated for the diagnosis of various types of cancers such as lung, colorectal, bladder and prostate cancer.

Could a simple breath test diagnose a disease? | Billy Boyle | TEDxUniversity of Cambridge

In the context of the early detection of lung and breast cancers, methylated hydrocarbons have been proposed as biomarkers. The scientists said the presence of acetaldehyde in exhaled air above 22 ppb could be of major clinical significance. Although acetaldehyde is an intermediate product in the metabolism of ethanol in the liver, alcohol consumption significantly elevates its levels in the breath. Scientists have determined the molecular emission of cancer cell lines CALU-1 and SK-MES and found its presence to be above physiological levels.

VOCs produced by gut bacteria are transported and excreted through the lungs. For example, the VOCs released by Helicobacter pylori in the human stomach can be detected in the air exhaled through the mouth. Helicobacter pylori infect the stomach and intestine, damage the tissues of the stomach lining and cause inflammation. This pathogen causes peptic ulcers in humans.

Scientists have designed a breath analyzer for the detection of pulmonary tuberculosis. In this case, the biomarker compounds detected are methyl p-anisate, methyl phenylacetate, oh-phenylanisole and methyl nicotinate.

Commercial production of breath analyzers for disease detection

Owlstone was formed by a group of scientists from the University of Cambridge, who made and sold “Field Asymmetric Ion Mobility Spectrometry (FAIMS)”. Their “Breath Biopsy” technology can accurately profile VOCs present in breath samples.

Breath Diagnostics, a Kentucky-based startup, has developed a respiratory diagnostic device for lung cancer. He said their device could distinguish benign from malignant tumors 77% of the time.

New England Breath Technologies is a Massachusetts-based start-up, which was founded in 2015. This company has developed a breath analyzer for blood sugar detection. Their product is called Glucair, which detects the concentration of acetone in an individual’s breath.

References

  • Lourenço, C. and Turner, C. (2014) “Breath analysis in disease diagnosis: methodological considerations and applications”, Metabolites, 4(2), p. 465-498. doi: 10.3390/metabo4020465.
  • Kaloumenou, M. et al. (2022) “Breath Analysis: A Promising Tool for Disease Diagnosis – The Role of Sensors”, Sensors, 22(3), p. 1238. doi: 10.3390/s22031238.
  • (2022) Cen.acs.org. Available at: https://cen.acs.org/articles/82/i13/BREATH-ANALYSIS-MEDICAL-DIAGNOSIS.html (Accessed: June 23, 2022).
  • Transforming Disease Detection: The Power of Breath Analysis (2021). Available at: https://www.medicaldevice-network.com/sponsored/transforming-disease-detection-breath-analysis/ (Accessed: June 23, 2022).
  • Mule, N., Patil, D. and Kaur, M. (2021) “A Comprehensive Survey of Exhaled Breath (EB) Investigation Techniques for the Diagnosis of Diseases of the Human Body”, Informatics in medicine unlocked, 26, p. 100715. doi: 10.1016/j.imu.2021.100715.


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