Towards collaboration and validation in breath research

We need to work together on larger trials and take advantage of the opportunities presented by targeted biomarker analysis. These are the key messages that emerged from the expert presentations and discussions at this year’s Breath Biopsy Conference. Taking place for the second time, the 2019 conference saw over 100 leaders in the breath research field and related areas coming together in Cambridge to discuss the latest advances and to drive progress in understanding breath biomarkers and advancing breath tests into clinical application.

Particular highlights from the program included keynote lectures from Jane Hill (Thayer School of Engineering, Dartmouth), Jessica Lasky-Su (Brigham & Women’s Hospital, Boston) and George Hanna (Imperial College London); A session on targeted stable isotope and exogenous VOC breath tests; and an enthusiastic and enlightening discussion session looking at predictions for the next five years in the field.

Chris Mayhew, Director of the Institute of Breath Research, University of Innsbruck, led the call for more cooperation within the breath community. He highlighted the abundance of small-scale discovery studies in the breath research field arguing that, despite decades of work, few proposed biomarkers have been thoroughly assessed and validated in larger-studies. Although technology has partly limited advancement, now is the time for groups around the world to come together to really make progress in demonstrating robust biomarkers for various diseases. In his presentation, which started off in the depths of space, Prof Mayhew reviewed the variety of chemical analysis tools that have been applied in the breath field and concluded that the study of endogenous breath biomarkers has yet to produce quality results, raising exogenous probes as a powerful alternative. In particular, he examined the use of probes and breath testing for liver disease, where bad breath (fetor hepaticus) is a long-standing diagnostic tool.

The message of collaboration was carried further by Jane Hill in her support for data parasitism, calling for greater reuse and meta-analysis of existing datasets – “There’s a big problem: How do you integrate data that people have done on different platforms, different study designs etc.” Prof Hill’s keynote looking at breath testing to detect infectious diseases, particularly in developing countries was received with particular interest by the audience. One of the goals of Prof Hill’s laboratory is to diagnose tuberculosis infections via breath testing in under an hour. She presented work using macaques as a model for infection, reliably identifying infected animals and efficiently predicting disease severity. She supported these results with preliminary studies in humans. Prof Hill encouraged more researchers to collaborate when doing animal studies to reduce the overall need for animal research. She also advocated for the application of animal breath tests in research to avoid unnecessary deaths, with the added benefit of reducing research costs.

One of the most exciting advances in validated breath biomarkers this year came in the form of a paper by Schleich et al. which we wrote about earlier in the year. Using patient cohorts in Liege, Belgium, the team identified biomarkers for differentiating asthma phenotypes and validated them using an independent patient cohort. This paper represents an important step forward for the breath research field and it was fantastic to hear from Renaud Louis about the medical implementation of this breakthrough work.

Another recent advance presented at the conference came from Owlstone Medical Metabolomics Scientist, Isabel Orf. In her presentation of our work developing exogenous volatile organic compound (EVOC) Probes, Dr Orf demonstrated preliminary results collected as part of the PAN Cancer Trial. This small pilot study uses the Breath Biopsy platform to validate previous work from Chris Mayhew and colleagues linking limonene levels on breath to metabolic changes related to liver failure. This ongoing work represents some of our first results in the process developing targeted breath analysis tools.

As the final Keynote speaker at this year’s conference, George Hanna, reinforced the need for validation of results in his discussion of the challenges for clinical validation studies. He shared meta-analysis figures demonstrating the quality of results that can be attained through exhaled breath analysis and illustrated the wide range of parallel biomarker discovery studies that have been performed. Beyond variation in methodology and lack of validation, he also explored the clinical, patient and environmental confounding factors that impact breath studies. Many of the challenges identified in this talk have previously been discussed in our blog post on challenges in breath research.

This year’s conference program ended with an expert panel discussion where we asked delegates to consider the opportunities and obstacles in the next five years of breath research. In a broadly optimistic and open discussion, the hope for more global collaborations and greater international cooperation was clear. The benefits of collaboration were particularly prominent in helping to understand and address the variation in breath samples between different populations and locations. There was also a strong interest in continuing to develop towards more point of care applications using targeted miniaturized technologies, such as those offered by FAIMS. This was paired with calls for more biological research to understand the metabolic origins of breath biomarkers. Generally, the panel were enthusiastic about the new research directions being made available through targeted approaches to breath testing. Echoing earlier sentiments, Paul Thomas reinforced the key message of the conference by saying: “Right now we’re waiting for these separate, isolated drops of knowledge to start to coalesce to form this pool of wisdom and I think that’s what we’re all seeking to achieve.”

As the event hosts, we at Owlstone Medical are excited to see all of the ongoing work being done in the breath research field. We enjoyed sharing our updated Breath Biopsy products with attendees and getting feedback on the updated designs. We’re grateful to everyone from the breath research community for taking part and we’d like to thank our sponsors Thermo Scientific, Markes International, SepSolve Analytical and LECO for making this year’s event possible. The posters, presentations and abstracts from this year’s conference are available online.