Respiratory infections are a leading cause of morbidity and mortality. Bacteria and viruses precipitate the majority of respiratory tract infections and also induce exacerbations in patients. Infection aetiology is particularly difficult to distinguish clinically and this represents a major unmet clinical need. Accurate identification of infection aetiology of respiratory infections would facilitate initiation of the most appropriate prompt management. There is evidence from in vitro and in

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... models that Volatile Organic Compounds (VOCs) can be measured through multiple analytical mass spectrometry platforms to differentiate between pathogens. The aim of this PhD is to investigate the utility of VOC measurements as a method of identification of infection aetiology and to determine whether such tests could be useful in differentiation of bacterial and viral exacerbations. Gas Chromatography- Mass Spectrometry (GC-MS) will be the primary method of analysis. Hypothesis Interaction between bacteria or viruses with their host results in different biochemical reactions. Metabolic degradation products including VOCs can be detected in exhaled breath and can be utilised to identify aetiology of exacerbations. Sub hypothesis • Pathogenic bacteria produce distinct VOCs that can be measured in the headspace following culture on agar medium. • Infection of airway epithelial cell cultures in vitro with pathogenic bacteria and respiratory viruses will lead to production of virus and bacteria specific VOCs that can be detected in the headspace. • Exhaled breath sampling following experimental infection with rhinovirus 16 in healthy subjects will identify VOCs that are upregulated following virus infection in vivo. • Targeted breath analysis in COPD patients during acute exacerbation will allow identification of pathogen-specific VOCs identified in sub-hypotheses 1, 2 and 3 Results In vitro agar plate growth of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) showed different VOC profiles which allowed for differ [...]