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1.
Exhaled volatile organic compounds and respiratory disease : recent progress and future outlook
Maria Chiara Magnano, Waqar Ahmed, Ran Wang, Martina Bergant Marušič, Stephen J. Fowler, Iain R. White, 2024, review article

Abstract: The theoretical basis of eVOCs as biomarkers for respiratory disease diagnosis is described, followed by a review of the potential biomarkers that have been proposed as targets from in vitro studies. The utility of these targets is then discussed based on comparison with results from clinical breath studies. The current status of breath research is summarised for various diseases, with emphasis placed on quantitative and targeted studies. Potential for bias highlights several important concepts related to standardization, including practices adopted for compound identification, correction for background inspired VOC levels and computation of mixing ratios. The compiled results underline the need for targeted studies across different analytical platforms to understand how sampling and analytical factors impact eVOC quantification. The impact of environmental VOCs as confounders in breath analysis is discussed alongside the potential that eVOCs have as biomarkers of air pollution exposure and future perspectives on clinical breath sampling are provided.
Keywords: breath analysis, disease diagnosis, exhaled volatile organic compounds, respiratory disease, environmental exposure analysis, breath analysis
Published in RUNG: 06.05.2024; Views: 201; Downloads: 3
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2.
Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma
Adam Peel, Ran Wang, Waqar Ahmed, Iain R. White, Maxim Wilkinson, Yoon K. Loke, Andrew M. Wilson, Stephen J. Fowler, 2023, original scientific article

Abstract: Background Inhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin. Methods Participants with a clinical diagnosis of asthma, or undergoing investigation for suspected asthma, were recruited. Inhaled mannitol challenges were performed, followed by a sham challenge after 2 weeks in participants with bronchial hyper-responsiveness (BHR). VOCs were collected before and after challenges and analysed using gas chromatography–mass spectrometry. Results Forty-six patients (mean (SD) age 52 (16) years) completed a mannitol challenge, of which 16 (35%) were positive, and 15 of these completed a sham challenge. Quantities of 16 of 51 identified VOCs changed following mannitol challenge (p<0.05), of which 11 contributed to a multivariate sparse partial least square discriminative analysis model, with a classification error rate of 13.8%. Five of these 16 VOCs also changed (p<0.05) in quantity following the sham challenge, along with four further VOCs. In patients with BHR to mannitol distinct postchallenge VOC signatures were observed compared with post-sham challenge. Conclusion Inhalation of mannitol was associated with changes in breath VOCs, and in people with BHR resulted in a distinct exhaled breath profile when compared with a sham challenge. These differentially expressed VOCs are likely associated with acute airway inflammation and/or bronchoconstriction and merit further investigation as potential biomarkers in asthma.
Keywords: asthma, exhaled volatile organic compounds, pulmonology, breath metabolomics
Published in RUNG: 31.07.2023; Views: 978; Downloads: 3
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3.
Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study
Pouline M van Oort, Iain R. White, 2019, original scientific article

Abstract: Volatile organic compounds in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae (SP) or Pseudomonas aeruginosa (PA) pneumonia can be discriminated from uninfected controls by thermal desorption-gas chromatography-mass-spectrometry (TD-GC-MS) and selected ion flow tube-mass spectrometry (SIFT-MS) of exhaled breath. Male adult rats (n = 50) received an intratracheal inoculation of 1) 200 µl saline, or 2) 1 × 107 colony-forming units of SP or 3) 1 × 107 CFU of PA. Twenty-four hours later the rats were anaesthetized, tracheotomized, and mechanically ventilated. Exhaled breath was analyzed via TD-GC-MS and SIFT-MS. Area under the receiver operating characteristic curves (AUROCCs) and correct classification rate (CCRs) were calculated after leave-one-out cross-validation of sparse partial least squares-discriminant analysis. Analysis of GC-MS data showed an AUROCC (95% confidence interval) of 0.85 (0.73-0.96) and CCR of 94.6% for infected versus noninfected animals, AUROCC of 0.98 (0.94-1) and CCR of 99.9% for SP versus PA, 0.92 (0.83-1.00), CCR of 98.1% for SP versus controls and 0.97 (0.92-1.00), and CCR of 99.9% for PA versus controls. For these comparisons the SIFT-MS data showed AUROCCs of 0.54, 0.89, 0.63, and 0.79, respectively. Exhaled breath analysis discriminated between respiratory infection and no infection but with even better accuracy between specific pathogens. Future clinical studies should not only focus on the presence of respiratory infection but also on the discrimination between specific pathogens.
Keywords: biomarkers, exhaled breath analysis, infection, pneumonia
Published in RUNG: 22.07.2019; Views: 3174; Downloads: 0
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4.
Headspace volatile organic compounds from bacteria implicated in ventilator-associated pneumonia analysed by TD-GC/MS
Oluwasola Lawal, Howbeer Muhamadali, Waqar M Ahmed, Iain R. White, Tamara M E Nijsen, Roy Goodacre, Stephen J. Fowler, 2018, original scientific article

Abstract: Ventilator-associated pneumonia (VAP) is a healthcare-acquired infection arising from the invasion of the lower respiratory tract by opportunistic pathogens in ventilated patients. The current method of diagnosis requires the culture of an airway sample such as bronchoalveolar lavage, which is invasive to obtain and may take up to seven days to identify a causal pathogen, or indeed rule out infection. While awaiting results, patients are administered empirical antibiotics; risks of this approach include lack of effect on the causal pathogen, contribution to the development of antibiotic resistance and downstream effects such as increased length of intensive care stay, cost, morbidity and mortality. Specific biomarkers which could identify causal pathogens in a timely manner are needed as they would allow judicious use of the most appropriate antimicrobial therapy. Volatile organic compound (VOC) analysis in exhaled breath is proposed as an alternative due to its non-invasive nature and its potential to provide rapid diagnosis at the patient's bedside. VOCs in exhaled breath originate from exogenous, endogenous, as well as microbial sources. To identify potential markers, VAP-associated pathogens Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were cultured in both artificial sputum medium and nutrient broth, and their headspaces were sampled and analysed for VOCs. Previously reported volatile markers were identified in this study, including indole and 1-undecene, alongside compounds that are novel to this investigation, cyclopentanone and 1-hexanol. We further investigated media components (substrates) to identify those that are essential for indole and cyclopentanone production, with potential implications for understanding microbial metabolism in the lung.
Keywords: bacteria, exhaled breath, infection, ventilator-associated pneumonia, volatile organic compounds
Published in RUNG: 18.07.2019; Views: 2944; Downloads: 0

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