Research that will take your breath away

Researcher and science blogger, Dr Simon Stott, writes a special post for us about his work on breath analysis in Parkinson’s. You can read more blog posts from Simon at scienceofparkinsons.com

Imagine a future in which you will be talking to a friend on the phone and the phone will be analysing your breath during the entire conversation. Monitoring your health and alerting your doctor if something strange is detected.

Or perhaps you will be arriving at your doctor’s office and you will need to speak into the intercom at the door to gain access to the building, and that intercom will analyse your breath for biological indicators (or ‘biomarkers’) of illness. You may simply be seeking treatment for a dose of the flu, but the intercom’s analysis will be able inform the doctor that they should also treat you for another condition (for example, diabetes) that is present, but yet to truly show itself.

This is the idea that underlies the breath analysis technology that is being developed by Prof Hossam Haick and his team at the Israel Institute of Technology (or Technion) in Haifa, Israel. They have developed a clever way of analysing the chemicals in one’s breath, and their research has found that certain combinations of chemicals relate to specific medical conditions.

Here in Prof Roger Barker’s lab at the University of Cambridge, we are collaborating with Prof Haick in an effort to use this technology to not only distinguish between people with and without Parkinson’s, but also to better differentiate the various sub-types of Parkinson’s that we think exist (for example, those who have more tremor problems versus those who have severe rigidity).

Don’t waste your breath

All of the activity inside your body generates a lot of waste. All of the cells are constantly active and need to keep themselves alive so as to perform some specific function. Eventually though, when a cell has served its function, it shuts down and dies. All of these different processes involved in the life span of each cell generates waste.

Now your body can expel waste into the eternal world via several methods, including urination and defaecation. Arguably, the most user-friendly of these exit points for waste is your breath. And researchers around the world have been investigating the use of the waste in your breath as a diagnostic aid for many medical conditions.

Every breath you take

Exhaled air is made up of nitrogen (78%), oxygen (18%), and carbon dioxide (4%), but it also contains tiny levels of chemicals that result from the biological processes in your body. Some of these chemicals are called ‘volatile organic compounds’ (VOCs).

VOCs are chemicals that have a low boiling point which means that they vaporise easily, and they are numerous and ubiquitous. Most of scents and odors we smell are VOCs, and as a result they play an important role in how plants and animals communicate.

VOCs are normally present in your breath but in very low quantities. For example, one of the most abundant VOCs in human breath is the chemical called isoprene, but it makes up just 12,580 part per billion (or 0.001%) of your breath. Despite these low levels, VOCs are readily detectable and Prof Haick’s team has developed a machine that can capture and analyse them.

It is called the Nanose device.

Sticking your (na)nose into the situation

In Cambridge, we are using the Nanose device to analyse the breath samples collected from 200 people with Parkinson’s (and 100 healthy controls).

The goal of the study is to firstly determine the potential of the technology to stratify people with Parkinson’s into particular subtypes and to track their progress overtime. Second, we will isolate and compare the VOCs identified in the breath samples with other biological samples we are collecting (eg. blood) from the same subjects. And thirdly, we will assess whether the origins of VOCs detected both in the breath and in other biological samples have a role in the neurodegenerative processes associated with Parkinson’s.

Using this approach, we hope to better diagnose and stratify people with Parkinson’s. Assigning them into particular subgroups will in turn we hope will help in the development of more specific treatments. We are also seeking to provide a user-friendly method for monitoring progression, which may also highlight novel biological pathways that are involved in the condition itself.

Tried and tested

The breath test analysis approach is not new. It has been used to investigate different respiratory, infectious and digestive conditions. Notably, the testing of individuals for infections of the gut with a bacteria called Helicobacter pylori, can be conducted using a simple breath test and it has been shown to work very well.

Indeed, our collaborators in Israel (Prof Haick’s team) have already conducted a small clinical study in which they could distinguish between 44 people with sporadic Parkinson’s, 16 people with genetic forms of Parkinson’s and 37 healthy controls. Using just breath samples from these people, they achieved a 90% accuracy rate — which was not affected by Parkinson’s treatments such as Levodopa (Nakhleh et al, 2015).

Prof Haick and his colleagues have subsequently published results investigating breath samples from 1404 people who have one of 17 different medical conditions, including Parkinson’s. That blind analysis exhibited an 86% accuracy rate in distinguishing between these conditions (Nakhleh et al, 2017).

Keeping one’s (na)nose to the grindstone

The current breath analysis study (co-funded by Parkinson’s UK and the British Council — BIRAX2) is ongoing, but preliminary results suggest that we can clearly distinguish between people who have had Parkinson’s for a long period compared to those just recently diagnosed, simply from a single breath sample. In addition, we can identify those with more severe symptoms relative to those with less advanced features. We are now exploring the many different features of Parkinson’s within the Parkinson’s-affected community to determine if their specific symptoms can be identified by a particular profile of VOCs in the breath.

Whether any VOCs being detected in the current study represent the biological consequences of neurodegeneration in the brain or simply changes in bacterial activity in the gut will need to be determined. But we are finding it rather remarkable that one can learn so much about a person from just a single breath.

For more information regarding the Parkinson’s UK/BIRAX2 breath analysis study, please see our website: https://www.barkerlab.co.uk

Simon is a post-doctoral researcher at the University of Cambridge. He writes about the latest research results in the field of Parkinson’s on his own blog at scienceofparkinsons.com.