Breath Testing Shows Promise as Reliable, Simple Method for Diagnosing FA, Other Diseases

Breath testing holds potential as an accurate, simple, and noninvasive diagnostic tool for Friedreich’s ataxia (FA) and other neurodegenerative diseases, a review suggests.

The study, “Emergence of breath testing as a new non-invasive diagnostic modality for neurodegenerative diseases,” appeared in the journal Brain Research.

Neurodegenerative diseases typically progress from a preclinical stage with alterations at the cellular level to mild cognitive impairment and later to more severe clinical phases.

Treating these disorders is more successful if it’s started before clinical symptoms become apparent. In this regard, biomarkers may not help achieve earlier diagnosis, but they may provide an opportunity for timely treatment.

Examining disease-related alterations in the brain (neuropathology) is considered the most accurate method of diagnosing neurodegenerative diseases. But the requirement of a surgical biopsy — or an autopsy if a patient dies — is a major limitation.

A neuropsychological assessment of memory, speech, or attention is a sensitive approach, but has low specificity to provide information about the progression of a specific disorder.

An additional option is analyzing the brain’s electrical signals, normally by electroencephalogram (EEG). Although recent tools have brought significant advances, evaluation of EEG data is subjective and may carry problems with result interpretation.

Neuroimaging, including magnetic resonance imaging (MRI), and CT or PET scans, provides information about the brain’s structure and function. But this strategy still lacks accuracy to reliably detect disease-specific atrophies at the preclinical stage and mild cognitive impairments in early disease development.

Molecular tests to analyze DNA or RNA are able to identify people at risk of developing specific neurodegenerative disorders in a cost-effective and accurate manner.

Biochemical analysis is an additional tool for early disease detection before cognitive impairment. However, invasive procedures to obtain samples may be an obstacle for long-term studies.

Despite this diversity of available approaches, new strategies that more closely depict brain function and clinical symptoms are needed, the authors said.

In particular, they’re in favor of the use of noninvasive biomarkers, which are better suited for both preclinical and clinical studies.

Human breath contains nitrogen, oxygen, carbon dioxide, water vapor, as well as many other components in very small (trace) amounts. An analysis of these components can provide detailed information about cellular health.

“Therefore, breath testing provides an interesting avenue of diagnostic opportunity to assess [disease-related] changes associated with various conditions in the body,” the investigators wrote.

The most widely used breath biomarkers include carbon disulphide, nitrogen or oxygen-containing compounds, hydrocarbons, and sulphur-containing substances.

Breath testing is routinely used to diagnose bacterial infections, transplant organ rejection, asthma, and evaluate blood-alcohol concentration. It also been used in several other conditions, including cancer and diabetes, and is able to differentiate between age groups.

Breath testing has recently been used to identify neurodegenerative disorders such as Friedreich’s ataxia,  Alzheimer’s, or Parkinson’s disease. This is primarily based on assessing metabolic changes related to dysfunction of mitochondria – the part of cells where power is produced – and oxidative stress, particularly in peripheral organs, such as the liver.

Monitoring disease progression can also be done by measuring concentrations of volatile organic compounds in exhaled breath samples.

The feasibility of breath testing for neurodegenerative disorders is supported by studies showing that this approach accurately differentiates between healthy and diseased tissues, and is also able to spot the difference between different disorders.

The researchers wrote that breath testing is easy to perform and analyze, and it is noninvasive and painless.

“Breath analysis could be used in combination with other diagnostic methods such as neuropsychological assessment, neuroimaging, and molecular analysis to increase overall diagnosis sensitivity and specificity of [neurodegenerative disorders],” the scientists wrote.

They added that breath testing may also be used to monitor the effectiveness of therapeutics and optimize treatments in animals before clinical testing.