The purpose of this study was to examine the relationships between inflammation, infection and lung function in cystic fibrosis during the evolution of lung disease in childhood and early adolescence. The developmental stages of childhood and the progression of lung disease together affected the methods and techniques used in the study, with the consequence that the work for this thesis fell naturally into two parts. The first part concerned the study of early lung disease in infants and young children who were unable to expectorate or to cooperate with lung function testing. In the second part, the inflammatory processes in both stable lung disease and during clinical exacerbations in older children and adolescents were studied non-invasively using sputum. The absence of a recognised definition of pulmonary exacerbation lead to further investigation into clinical heterogeneity in the diagnosis and management of an exacerbation. In early lung disease, inflammation was not found to be independent of infection, with pathogens in the lower airways found to correlate with levels of inflammation, respiratory system compliance and degree of air trapping (a relationship not previously shown). This suggested that infection remains the key target to minimizing lung damage in cystic fibrosis. The relationship between sputum markers of inflammation and lung pathology in established disease was found to be less clear, with high inflammation levels in both stability and during exacerbation. Reduction in sputum inflammatory levels following treatment of an exacerbation was found to be greater in those with lower pre-treatment levels. The definition and management of an exacerbation was found to be an area lacking consensus among clinicians, with likely consequent heterogeneity of clinical care and therefore inhomogeneity of hospitalization as a surrogate measure of exacerbation in a research setting. The work from this thesis, and the ensuing publications, has contributed to the understanding of the interactions between the inflammatory and infectious processes involved in CF lungdisease, in both early and more established lung disease in childhood.
| Identifer | oai:union.ndltd.org:ADTP/272627 |
| Date | January 2009 |
| Creators | Dakin, Carolyn , Women's & Children's Health, Faculty of Medicine, UNSW |
| Publisher | Awarded by:University of New South Wales. Women's & Children's Health |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Dakin Carolyn ., http://unsworks.unsw.edu.au/copyright |
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