Giuseppe Ferrandino at the 2020 Breath Biopsy Conference

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Talk Abstract:

Background: Exhaled limonene levels are elevated in patients with cirrhosis as a result of reduced hepatic clearance due to impaired liver function. The goal of this study is to identify additional EVOCs to couple with limonene to maximize diagnostic performance of a breath test for liver function.

Methods: Breath biopsies from 46 patients with cirrhosis (14 non-alcoholic steatohepatitis (NASH), 19 alcoholic, 13 others) and 42 age- and gender-matched healthy controls were collected using the ReCIVA® Breath Sampler. Samples were analysed by thermal desorption gas chromatography mass spectrometry, using a Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometer. Feature extraction and tentative identification was performed using Compound Discoverer™ complemented with a manual approach.

Results: Nineteen of 277 identified compounds showed discriminatory potential for cirrhosis. Limonene coupled with four of these compounds yielded an area under the ROC curve (AUC) > 0.9 for training and test sets. Principal component analysis (PCA) on discriminatory compounds showed a separation between cirrhotic and healthy controls along PC1 and PC2, explaining 50% and 9% of data variance respectively. This separation was mainly driven by cirrhosis severity determined by the Child-Pugh scoring.

Conclusions: We identified a subset of exhaled volatile compounds that, coupled with limonene, maximize diagnostic performance for cirrhosis. The extent of alterations of these compounds in breath is determined by disease severity. Discriminatory performance of these potential biomarkers suggests their suitability for a novel breath test for the non-invasive detection of cirrhosis. Future work will expand these observations into larger cohorts that include patients with earlier stages liver disease such as NASH.

Giuseppe Ferrandino¹, Giovanna De Palo¹, Antonio Murgia¹, Rob Smith¹, Anita Kaur Thind¹, Irene Debiram-Beecham², Olga Gandelman¹, Alexandra de Saedeleer¹, Graham Kibble², Anne Marie Lydon², Chris A. Mayhew^3,4, Agnieszka Smolinska^1,9, Max Allsworth¹, Billy Boyle¹, Marc P. van der Schee¹, Michael Allison^5,8, Rebecca C. Fitzgerald¹⁰, Matthew Hoare^6,7,8, Victoria K. Snowdon⁸

1. Owlstone Medical, 183 Cambridge Science Park, Milton Road, Cambridge CB4 0GJ, UK.
2. Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Box 197
Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XZ, UK.
3. Institute for Breath Research, Leopold-Franzens-Universität Innsbruck, Rathausplatz 4, A 6850,
Dornbirn, Austria
4. Molecular Physics Group, School of Physics and Astronomy, University of Birmingham,
Edgbaston, Birmingham B15 2TT, UK.
5. Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University
Hospitals NHS Foundation Trust, Cambridge, UK.
6. CRUK Cambridge Institute, Cambridge, UK.
7. Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
8. Addenbrookes Hepatology and Liver Transplantation Unit, Addenbrookes Hospital, Cambridge.
9. Department of Pharmacology and Toxicology, School for Nutrition and Translational Research
in Metabolism (NUTRIM), Maastricht University Medical Center, the Netherlands.
10. MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.

Speaker Biography:
Giuseppe’s keen interest in the study of NAFLD arose during his post-doctoral experience at Yale School of Medicine in the USA, where he contributed to discovering the link between hypothyroidism and NAFLD. He provided significant support to several other research projects ranging from ion transport to the characterization of a new drug for thyroid cancer treatment.

Giuseppe then moved to Dresden, Germany, joining the Max Planck Institute of Molecular Cell Biology and Genetics as a post-doctoral scientist. In the two years there, he focused on the identification of a signalling pathway that promotes lipid accumulation in the liver. This pathway may underlie the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a metabolic disorder affecting 25% of the European population.

Despite advanced new technologies, liver biopsy remains the gold standard to diagnose NAFLD and other liver conditions. At Owlstone Medical, Giuseppe contributes to replacing this invasive diagnostic procedure with a simple Breath Biopsy, aiming to promote early diagnosis, when most liver diseases are easily defeated.

On a personal note, Giuseppe enjoys his favorite hobby, cooking, with an affable company. He had the opportunity to train at a professional level in his homeland, Ischia, a beautiful island immersed in the blue of the Gulf of Naples in Italy. A place where Giuseppe loves to admire colorful sunsets by the sea.

The 2021 Breath Biopsy Conference is scheduled for 12th & 13th October. Click the button to express interest in the next Breath Biopsy Conference:

Express Interest