VOC breath biomarkers for early detection and monitoring of acute pulmonary exacerbations in people with Cystic Fibrosis

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 diagnosis of APE and treatment monitoring due to insensitive measurements and subjective self-reported symptoms. Volatile organic compounds (VOCs) in exhaled breath have demonstrated potential as a non-invasive tool for disease diagnosis and monitoring. The metabolic change captured in breath could provide early signals for APE, as opposed to lung function measurements, which occur in later stages. Five subjects provided 4 breath samples: 3 samples at 7-day intervals while taking antibiotics, and 1 after treatment. Samples were analyzed using Breath Biopsy^® OMNI^® via TD-GC-MS. The Friedman test was selected to compare the abundance of each VOC across the repeated breath measurements of all patients. The Wilcoxon signed-rank test was selected to compare VOC changes in subjects at recruitment and at the end of treatment monitoring, as well as to compare changes at recruitment and the follow-up appointment. 1007 VOCs were identified through untargeted analysis, with 69 VOCs exhibiting significant change and 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/or impact of antibiotics on the microbiome. This identifies several compounds with the potential to discriminate baseline from initial exacerbation, as well as the effects of antibiotic treatment on initial exacerbation.