Generation mechanisms of hydrogen cyanide and ammonia in human exhaled breath

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Title: Generation mechanisms of hydrogen cyanide and ammonia in human exhaled breath
Author: Chen, Wen
Contributor: University of Helsinki, Faculty of Science, Department of Chemistry
Thesis level: Doctoral dissertation (article-based)
Abstract: Human exhaled breath contains hundreds of volatile compounds. Breath analysis is a method of seeking biomarkers among these volatiles, which could potentially serve as non-invasive medical indicators in disease diagnosis. With the development of analytical techniques more disease-related breath volatiles are being discovered. Exhaled hydrogen cyanide (HCN) and ammonia (NH3) have been studied previously. Both of them are potential biomarkers in clinical practice. Breath HCN has been proposed as a biomarker of Pseudomonas aeruginosa colonization in cystic fibrosis patients, since high levels of HCN are detected in the headspace of P. aeruginosa in vitro. Breath NH3 has been suggested as an indicator for monitoring hemodialysis (HD) adequacy in end-stage renal disease (ESRD) patients, since breath NH3 is strongly correlated to blood urea. To validate breath HCN and NH3 tests for clinical application, one has to understand the biochemical mechanisms of breath HCN and NH3 production in the human body. In some earlier studies, it was assumed that the oral cavity is a major production site for both breath HCN and NH3. However, the biochemical pathways of oral HCN and NH3 production have not been extensively studied. In this thesis, we investigated the correlation between salivary HCN and breath HCN in healthy subjects and confirmed that saliva is the main source for breath HCN. Additionally, we observed that oral anaerobes, including the genus of Porphyromonas, Prevotella and Fusobacterium, produce low levels of HCN in vitro. This implies that oral bacteria probably contribute to breath HCN generation. To explore the mechanism of breath NH3 production, we first conducted experiments on healthy subjects and found that salivary urea is the main source of breath NH3. We extended our study to ESRD patients during their HD treatment to investigate the connection between blood urea and breath NH3. Through the observation of strong correlations between blood urea, salivary urea, salivary ammonia and breath NH3, we were able to suggest a biochemical pathway for breath NH3 production. Blood urea is diffused into saliva through salivary glands. Salivary urea is subsequently hydrolysed into ammonia by urease activity. Finally, salivary ammonia evaporates into the gas phase and becomes breath NH3.--
URI: URN:ISBN:978-951-51-2679-5
Date: 2016-11-15
Subject: physical chemistry
Rights: This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.

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