University of Twente Student Theses


Detection of Staphylococcus aureus and Aspergillus fumigatus infections in exhaled breath of cystic fibrosis patients

Golbach, E.M. (2021) Detection of Staphylococcus aureus and Aspergillus fumigatus infections in exhaled breath of cystic fibrosis patients.

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Abstract:Cystic fibrosis (CF) is the most life-threatening monogenic disease in western populations caused by mutation in the CF transmembrane conductance regulator (CFTR). The survival age of new-born CF patients in 2016 was 47.7 years. The disease causes damage to all organs consisting of epithelial cell membranes, mostly affecting the lungs. CF is characterized by thickened mucus in the lungs that can obstruct the airways and hinder the removal of pathogens, causing bacterial infections. The most common bacterial infections in CF patients are Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus), both associated with greater risk of exacerbations, hospitalisations, and decline of lung function. A fast and sensitive screening method for pathogens in the lungs is needed to successfully treat the infections at an early stage and prevent further harm. A possible solution might be the detection of volatile organic compounds (VOCs) in exhaled breath. This study aimed to identify candidate VOCs from literature linked to S. aureus and A. fumigatus in exhaled breath using the method of gas chromatography-mass spectrometry (GC-MS). The second objective was to assess if these VOCs can be used to distinguish S. aureus and A. fumigatus and P. aeruginosa in exhaled breath. Methods - To identify candidate VOCs that can possibly distinguish S. aureus and A. fumigatus in exhaled breath a systematic review of previous literature is conducted. These candidate VOCs are then examined in the in-vivo GC-MS breath data, originating from the BioMerieux study, a longitudinal study focused on exhaled breath of CF patients. The VOCs present in the breath samples were then compared to microbiology results (sputum and cough swaps) after which the targeted VOCs are analysed with multiple analyses. This study used univariate (Mann-Whitney U test), multivariate (PLS-DA) and topological (mapper) methods to analyse and assess the performance of breath data to predict pathogen presence. Results - In a total of 16 articles, 10 candidate VOCs coupled to the presence of S. aureus were found, and 6 articles resulted in one compound to link to A. fumigatus. Complete data (GC-MS and microbiology) was available from 54 patients, 29 adults and 25 children. Benzaldehyde displayed a significant difference (p < 0.05) between the S. aureus positive versus negative sputum samples as well as the S. aureus chronically infected versus not-chronically infected groups, with a AUROC of respectively 0.61 and 0.62 these groups could not be distinguished. Using PLS-DA and mapper did not deliver group distinguishing results. In the search for a discriminating compound for A. fumigatus α-pinene displayed a significant difference (p < 0.05) between positive versus negative sputum samples, with a AUROC of 0.62. Applying multivariate analysis strategies, PLS-DA and mapper, did not increase the discriminatory power between groups. Using all the candidate VOCs linked to S. aureus and A. fumigatus combined with previous research to compounds for P. aeruginosa a difference can be seen between groups of samples infected with S. aureus, A. fumigatus, and uninfected samples and groups that next to these samples also contain multiple infections. Discussion - Combinations of mass and retention time were significantly different between colonised and not colonised samples for both S. aureus and A. fumigatus. However, these specific data columns are not confirmed by other mass and retention time combinations linked to these same candidate VOCs making it is less plausible that these VOCs as discriminating. This study was the first to validate previous literature found in a systematic review using a targeted analysis with in vivo GC-MS data for S. aureus or A. fumigatus. Previous work of Kos et al. performed a similar protocol, using different compound confirmation in their breath samples and statistical methods. For future research, the mapper method could be of use to validate a suspected relationship between compounds and the presence of the pathogens. However it is difficult to quantify such relationships as mapper relies on visual analysis. Using exhaled breath is a non-invasive, low-cost, and time-efficient way of checking patients. However, more research should be done before it could be used in practice. When the performance of these methods will increase, exhaled breath has the right benefits to improve the possibilities in home monitoring. Conclusion - This study found several components to be associated with S. aureus and linked one component with A. fumigatus in literature, but was not able to extract significant candidate VOCs to discriminate positive and negative samples for both S. aureus and A. fumigatus by using GC-MS data.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:44 medicine
Programme:Technical Medicine MSc (60033)
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