Melbourne School of Population and Global Health - Theses
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ItemAssociations between biomarkers in exhaled breath condensate (EBC) and allergic disease phenotypes and lung function( 2016)Asthma is a common chronic disorder of the airways that involves a complex interaction of airflow obstruction, bronchial hyperresponsiveness and underlying airway inflammation. It is increasingly clear that asthma is a heterogeneous group of conditions (phenotypes) with common symptoms. The underlying mechanisms of different phenotypes are not clearly understood and the treatment responsiveness and causative factors are likely to vary between phenotypes. The increasing interest in airway inflammatory biomarkers assessment has led to the development and evolution of tools to measure these biomarkers which identify various asthma phenotypes. Exhaled breath condensate (EBC) is a totally non-invasive, easy to perform, feasible and inexpensive method for sampling lung and airways fluid, which reflects the airway epithelial lining fluid (ELF). EBC comprises a variety of airway inflammatory mediators, such as oxidative stress and pH, which provides non-invasive indicators of ongoing biochemical and inflammatory activity in the airways. Although EBC samples the entire respiratory tract from the mouth to the alveoli, the precise origin of each sampled molecule cannot be determined. A number of studies have assessed the relationship between EBC biomarkers and adult airway diseases, such as asthma. However, these studies have had limited sample sizes and, as a result, were unable to compare associations between numerous phenotypes of airway diseases. It remains possible that the associations with EBC biomarkers may change with age, but this has not been examined in a single study using the same methods. Furthermore, previous studies have been conducted in clinical populations rather than epidemiologic settings. Therefore, the overall aim of this PhD research was to assess the associations between oxidative stress biomarkers and pH in EBC and asthma phenotypes, rhinitis phenotypes, atopic sensitisation, lung function and objective markers of airway inflammation, including bronchial hyperresponsiveness (BHR) and the fraction of exhaled nitric oxide (FeNO), in both the early adulthood and middle-aged groups. Within this thesis, cross-sectional analyses nested within the two Australian longitudinal studies have been performed. These studies are: (1) The Melbourne Atopy Cohort Study (MACS), a study of individuals with a family history of allergic disease (defined as the early adulthood group in this thesis); and (2) The Tasmanian Longitudinal Health Study (TAHS), a population-based study (defined as the middle-aged group in this thesis). EBC samples were collected at the 18-year follow-up of MACS and the BHR LAB Study of the 5th-decade follow-up of TAHS. Using these data, this thesis contributes knowledge to the field, specifically addressing the following issues: Methodological issues from the laboratory analysis of EBC biomarkers Findings from this doctoral research showed that EBC biomarkers were influenced by the long period of storage, particularly for hydrogen peroxide (H2O2). The vast majority of analysed samples for H2O2 were shown to be below the lower limit of detection (LOD). In addition, both decreased levels of EBC total nitric oxide products (NOx) and increased EBC pH were associated with a long period of sample storage. Therefore, the duration of sample storage was adjusted for in all analyses presented in this thesis. Associations between EBC NOx and different phenotypes of asthma and rhinitis, sensitisation, lung function, BHR and FeNO This PhD research showed that atopic asthma and atopic rhinitis phenotypes were associated with higher levels of EBC NOx. Also, atopic sensitisation was related to increased levels of EBC NOx and this association was stronger in individuals with poly- aero-sensitisation. These findings were generally consistent across the two age groups. In the early adulthood group only, elevated levels of EBC NOx were associated with reduced pre- and post-BD FEV1/FVC. Additionally, EBC NOx was not related to BHR and FeNO. Therefore, EBC NOx may be considered a marker for allergic airway inflammation in different age groups. Associations between EBC pH and different phenotypes of asthma and rhinitis, sensitisation, lung function, BHR and FeNO Reduced EBC pH was associated with the presence of asthma and strongly associated with severity of asthma symptoms, as well as atopic asthma and atopic rhinitis in the early adulthood group. Also, similar associations were observed in those with atopic sensitisation, particularly in those who were sensitised to more than one tested allergen. However, none of the above associations were observed in the middle-aged group, suggesting that these effects may be age-dependent. Alternatively, it may be due to differences in methods used between the projects (e.g. degree of deaeration of the sample post collection). In addition, there were no associations between EBC pH, lung function, BHR, and FeNO in either project. These findings suggest that associations between airway acidification and asthma and sensitisation phenotypes may be influenced by the age of an individual. Conclusion Overall, my doctoral work observed some novel and interesting associations. Results from this thesis will aid the current understanding of an underlying inflammatory process, help to discriminate between different phenotypes of airway diseases and help guide future research. Although EBC is a promising method, it lacks appropriate standardisation and reference values and is therefore not currently suitable for use in clinical practice.