Breath Biopsy® Reveals Promising Voc Biomarkers For Early Detection And Monitoring Of Acute Pulmonary Exacerbations In People With Cystic Fibrosis

Hsuan Chou (1), Amy Craster (1), Ibrahim Karaman (1), Lucy Godbeer (1), Huw Davies (1), Agnieszka Smolinska (1), Billy Boyle (1), Max Allsworth (1), Lucy Gale (2,3), Andres Floto (2,3)  

(1) Owlstone Medical, Cambridge, UK. 2Department of Medicine, University of Cambridge, Cambridge, UK. 32Cambridge Centre for Lung Infection, Royal Papworth Hospital NHS Foundation Trust

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Abstract

Early detection of acute pulmonary exacerbation (APE) in cystic fibrosis (CF) patients is crucial for providing appropriate clinical intervention and minimizing lung function decline. The challenge remains in diagnosing APE and treatment response monitoring due to insensitive measurements and subjective patient-reported symptoms. Volatile organic compounds (VOCs) are produced by various physiological processes, and VOCs in breath have demonstrated great potential as a non-invasive tool for diagnosis and monitoring. The metabolic changes captured in breath could provide early signals for APE as opposed to lung function measurements, where changes occur later during an exacerbation. 

This study utilized Breath Biopsy® technology to identify novel VOC biomarkers for early detection of APEs in CF to enable diagnosis and treatment monitoring. Profiling of breath VOCs was performed shortly after the onset of an APE through the resolution to a stable baseline. 

Five adult subjects provided four breath samples over time. Three breath samples were collected at seven-day intervals while subjects were taking antibiotics and being monitored. The last breath sample was collected after treatment completion. The samples were analyzed using the Breath Biopsy® OMNI® Platform via TD-GC-MS. The Friedman test was selected to compare the abundance of each VOC across the breath measurements of all CF patients. The Wilcoxon signed-rank test was selected to compare VOC changes in CF subjects at recruitment, the end of treatment monitoring, and follow-up appointments. 

Of the 1007 breath VOCs identified, 69 exhibited significant changes across the entire time course of breath collection, with 39 compounds exhibiting a large effect size (Kendall’s W value ≥ 0.5). VOCs that differed between APE, treatment monitoring, and upon baseline return pointed toward the involvement or influence of inflammation, bacterial infection, and impact of antibiotics on the microbiome. 

This study utilized exhaled breath to establish VOC profiles in CF subjects with exacerbation from CF baseline. The results identified several compounds with the potential to discriminate baseline from initial exacerbation, as well as the effects of antibiotic treatment on initial exacerbation.