Preliminary method for profiling volatile organic compounds in breath that correlate with pulmonary function and other clinical traits of subjects diagnosed with cystic fibrosis: a pilot study

Abstract

Cystic fibrosis (CF) is characterized by chronic respiratory infections which progressively decrease lung function over time. Affected individuals experience episodes of intensified respiratory symptoms called pulmonary exacerbations (PEx) which accelerate pulmonary function decline and decrease survival. There is no standard classification for PEx, which results in treatments that are heterogeneous. Improving PEx classification and management is a significant priority for people with CF. Previous studies have shown volatile organic compounds (VOCs) in exhaled breath can be used as biomarkers because they are products of metabolic pathways dysregulated by different diseases. To provide insights on PEx classification and other clinical factors, exhaled breath was collected from subjects with CF, with some experiencing PEx and others at baseline. Exhaled breath was collected in Tedlar bags during tidal breathing for VOC analysis by solid phase microextraction coupled to gas chromatography–mass spectrometry. Statistical significance testing between quantitative and categorical clinical variables displayed percent-predicted forced expiratory volume in one second (FEV1pp) was decreased in subjects experiencing PEx. VOCs correlating with other clinical variables (body mass index, age, use of highly effective modulator therapies, and need for antibiotics) were also explored. VOCs correlating to potential confounding variables were removed and analyzed by regression for correlations with FEV1pp measurements. The VOC with the highest correlation with FEV1pp (3,7-dimethyldecane) also gave the lowest p-value when comparing subjects at baseline and during PEx. Receiver operator characteristic curves showed 3,7-dimethyldecane had a higher ability to classify PEx (area under the curve (AUC) = 0.91) relative to FEV1pp values at collection (AUC = 0.83). However, normalized ΔFEV1pp values had the highest capability to distinguish PEx (AUC = 0.93). These results show that exhaled VOCs may be a source of biomarkers for various clinical traits of CF, including PEx, that should be explored in larger sample cohorts and validation studies.

Real-time breath metabolomics to assess early response to CFTR modulators in adults with cystic fibrosis: an open-label proof-of-concept study

“…A few VOCs normalised after one month mirroring a short-term impact of the treatment, whilst others progressed more slowly possibly indicating a delayed effect. Furthermore, the evolution of several breath VOCs correlated with clinical outcomes which builds upon recent findings by Woollam et al Using GC-MS, they identified a set of VOCs correlating with ppFEV1 in CF patients experiencing pulmonary exacerbations [30]. In our study, eight VOCs significantly modified upon treatment were also consistently (at both V2 and V3) associated with variations in lung function (ppFEV1 or ppFVC).…”

“…These belong to the large range of carbonyl compounds that can be generated through lipid peroxidation, and which have been repeatedly associated with oxidative stress [33]. Woollam et al also observed a downregulation of longer aldehydes (octanal and nonanal) in patients treated with CFTR modulators [30]. Another significant VOC, dimethylformamide has been recently associated with dysfunctions in mitochondria [34] and glucose metabolism [35].…”

GC-MS-based metabolomics of volatile organic compounds in exhaled breath: applications in health and disease. A review

“…However, no single VOC was found significantly altered when applying UVA between stable and CF PEx patients. Meanwhile, Woollam et al (2022b) divided the CF patients into CF baseline (not suffering from PEx) and CF PEx. Four VOCs were found to be correlated with FEV1pp at the time of breath collection, of which two VOCs (4-methyl-octane and 3,7-dimethyldecane) were further correlated with changes in FEV1pp.…”

The Non-Invasive Detection of Pulmonary Exacerbations in Disorders of Mucociliary Clearance with Breath Analysis: A Systematic Review

“…Most studies were based on a paediatric population ( n = 16), and in 11 cases, adults were excluded. Four articles reported on exhaled VOCs measured with GC-MS [ 13 , 14 , 15 , 16 ], two papers concerned eNose-driven work [ 17 , 18 ] and one manuscript was focused on hydrogen cyanide in exhaled breath [ 19 ]. Biomarkers in exhaled breath condensate were measured in 11 studies.…”