Breath Test Diagnosis
Swansea University researchers say breath tests could revolutionize early disease diagnosis before any symptoms have developed, and without invasive procedures.
By Dr Masood Yousef
Senior Research Assistant in the Welsh Centre for Printing and Coating,
School of Engineering, Swansea University
Techniques for monitoring solvent levels in the breath of print machine operators as a result of occupational exposure are being adapted to develop breath testing procedures for diagnosing diseases by detecting "biomarkers" indicative of particular illnesses.
A joint collaboration in Swansea University between the Welsh Centre for Printing and Coating, Medical School and the Centre of Nanotechnology will explore the role of biomarkers in breath with eventual application to “off the shelf” printed diagnostic sensors.
Studies have shown that high concentrations of certain volatile organic compounds (VOC’s) in breath can correlate with disease for example, the odour of “pear drops” esters and acetone in relation to diabetes, ammonia in relation to hepatitis, and dimethyl sulphide to cirrhosis.1
It is speculated that a number of other illnesses may be diagnosed by the presence of an atypical compound or series of compounds in the breath of affected individuals.
Diagnostic techniques based on exhaled breath are much less developed than traditional serum or urine analysis techniques and not widely utilized in clinical practice. Diagnosis based on smells has been characterised as being crude, subjective and unreliable. Due to new improved analytical methodology, volatile marker based diagnostics has a new potential in both diagnosis and monitoring of illness.
It is a more convenient and rapid method than serum or urine analysis, requiring minimal medical intervention. Above all breath samples are easier to obtain than serum and urine, for both the sampler and the patient, and can be collected anywhere and by people with no medical training. Breath samples pose no biohazard risk and the procedure has the potential to be more cost effective than conventional methods.
There are growing developments for daily monitoring using non invasive breath analysis. This analysis has the potential to be rapid in applications across many fields in medicine including vetinary medicine.
Analysis of trace components in air requires the sampling of large volumes. The principle of breath sample collection is based upon the assumption that in the alveolar portion of the lungs, the concentration of VOC’s in blood is in equilibrium with the concentration in the air. This is because both capillary blood vessel walls and alveolar walls are thin enough to allow the free exchange of chemicals through the tissue membranes.1
During breath sampling, the individual exhales into a breath sampler until the lungs are as empty as possible. It has been estimated that an adult exhaling deeply expels at least four litres of air of which at least two litres comes from the alveolar air.2
A bespoke breath sampler holds 129ml of air and typically one litre of alveolar air is required to pass in order to ensure an undiluted sample. The breath sample is then transferred onto a sorbent tube which traps the volatile content ready for analysis.
Using GCMS-TD (gas chromatography, mass spectrometry and thermal desorption) new state-of-the-art analytical equipment it is now possible to produce a very high concentration enhancement of the breath volatiles with exceptional detection limits being achievable.3
In the past, conventional analytical methods involving either head space or solid phase micro extraction (SPME) have been utilised which require some element of sample preparation. These techniques have limitations and the sensitivity is limited in relation to thermal desorption. New emerging technologies are being developed and have been reported for lung related dysfunctions4,5 and is one of increasing interest.
The instrumentation available in Swansea has advantages compared to recent developments, as no sample preparation is required and large quantities of breath can be sampled onto a sorbent trap. The equipment also allows for enhancement of the final concentration 1000 fold, thus overall injecting a small highly enriched plug allowing trace components to be visualized.
For the reasons detailed above, non-invasive diagnostic strategies aimed at identifying biomarkers in breath samples of patients for the early detection of specific disease is of great interest.
If unique markers for specific diseases can be recognised earlier than traditional techniques, then there is potential to revolutionise early disease diagnosis before any symptoms have developed, without invasive procedures.
The presence of biomarkers may be specific to diseases, thereby having the potential to be a rapid diagnostic for conditions and has the potential for monitoring therapy and recovery. This would obviate the need for invasive blood testing which often requires painful arterial sample collections.
If a feasibility study was to prove biomarkers are present in a larger consensus of people with illnesses then this could lead to a pursuit of a nano-detection product with specificity. The product should be selective and only give positive results for subjects exhaling trace VOCs due to a particular illness. On completion of the project we can then explore the application to other diseases.
Success will ultimately lead to the development of new cost effective techniques for rapid identification of illnesses from breath.
The long-term aims of the research include:
• The use of breath markers for routine medical examinations, prior to symptoms arising, resulting in early onset diagnosis.
• The use of breath markers to monitor progression and severity of disease to allow adjustment of medication accordingly.
• Development of simplistic diagnostic tools such as test strips which will give positive results for specific illness markers, thus reducing the cost and level of expertise for diagnosis.
References:
1. W Cheng, W Lee. Journal of Lab. and Clin. Med. March 1999 (Vol. 133 No. 3)
2. Markes International Publication note 13 www.markes.com
3. Markes International Publication note 27 www.markes.com
4. M Phillips et al. Tuberculosis (2007) 87, 44-52
5. M Phillips et al. The Cardiopulmonary and critical care journal, (2003) 123,6.
