Research Doctorate - Doctor of Philosophy (PhD) / Airway inflammation is a key feature of asthma. Currently, airway inflammation can be detected through both invasive and non- invasive methods. Non invasive methods are safe, feasible and a potentially useful way to assess airway inflammatory markers in both healthy children and children with asthma. In this thesis, a variety of non-invasive markers (induced sputum, exhaled nitric oxide, and exhaled breath condensate) was used to investigate childhood asthma. The aim of the first study was to compare and contrast the different airway markers between healthy children and children with asthma. The second study described the different airway inflammatory phenotypes in children with asthma, and examined clinical predictors of these phenotypes; whereas the third study investigated the effects of environmental tobacco smoke (ETS) exposure on airway inflammation in childhood asthma. The final study assessed the knowledge and attitudes of parents of children with asthma towards passive smoking. The studies used both cross- sectional and longitudinal designs. Children with stable asthma aged between 7 - 17 years underwent clinical assessment, spirometry, exhaled nitric oxide (FeNO), exhaled breath condensate and sputum induction. Urinary cotinine was assayed to assess tobacco smoke exposure. These studies have found that children with asthma show differences in both clinical pattern and pathological pattern compared to healthy children. These differences were apparent with elevated FeNO and sputum eosinophils. In children with asthma, there was heterogeneity of airway inflammation. There were 2 stable inflammatory patterns: eosinophilic asthma and paucigranulocytic asthma. Unlike adult asthma, these phenotypes have different clinical features, which may facilitate detection of the phenotypes in clinical practice. ETS exposure in children with asthma was common and associated with a non- eosinophilic pattern of airway inflammation. In children who had a change in ETS exposure, sputum eosinophils were decreased whereas sputum neutrophils were increased during ETS exposure compared to a non- ETS exposure period. Fractional exhaled nitric oxide levels were decreased after exposure to ETS compared to those at the time of non- ETS exposure. The severity of asthma was increased in children living with parents who smoked. As a result, parents of children with asthma, especially smoking parents should be more aware about the harmful effects of smoking on their children’s health and themselves. Health risk awareness about tobacco smoke helps parental smokers alter their smoking behavior as well as protecting children from ETS exposure. In conclusion, the important findings of this thesis are the description of the inflammatory phenotypes in childhood asthma, the identification of clinical predictors of these phenotypes and the determination of the effects of ETS exposure on airway inflammatory patterns in childhood asthma. These results should facilitate understanding and management of childhood asthma and prompt treatment studies based on markers of airway inflammation.

Obstructive sleep apnoea (OSA) is a common disorder characterized by repetitive closure of the upper airway during sleep and associated with significant adverse health effects including hypertension, heart disease and stroke. Current treatment with continuous positive airway pressure (CPAP) is highly effective but reduced compliance levels have resulted in suboptimal outcomes. Oral appliances such as mandibular advancement splints (MAS) are an alternative treatment and have potential advantages including greater patient compliance, comfort and portability. Although they have been shown to be successful across all categories of OSA severity, overall they are less effective than CPAP. A key limitation to its more widespread use has been the inability to predict which patients will be a treatment success. Prediction of treatment outcome would greatly enhance both MAS utilization and overall OSA management. However, little is known about the mechanisms of action of MAS therapy and a more detailed understanding is likely to improve patient selection and outcome. The aim of this thesis is to improve the prediction of treatment outcome through improved understanding of the mechanisms and site(s) of action of MAS therapy during sleep, through extrapolating this knowledge into daytime prediction tests and by developing prediction equations which can be tested prospectively. The work in this thesis presents novel ideas and findings. It is the first to examine and find that MAS therapy improves upper airway collapsibility during sleep. The site(s) of upper airway collapse was also examined and found to predict treatment outcome. Primary oropharyngeal collapse during sleep predicted treatment success and this was extrapolated into a simple daytime test hypothesized to reflect oropharyngeal function. These primary oropharyngeal collapsers were found to have characteristic awake flow-volume curves and this was then studied prospectively. Cephalometric X-rays and anthropomorphic measurements were also evaluated to formulate prediction equations for treatment outcome with MAS. These new findings together with their implications for clinical practice and future research are then summarized. It is concluded, however, that although many advancements have been made, the mechanisms of MAS action and prediction of treatment outcome remain incompletely understood reflecting the complex pathophysiology of the upper airway.

No description available.

Thesis (Ph. D.)--University of Canterbury, 2007. / Typescript (photocopy). "November 2007." Includes bibliographical references (p. 241-278). Also available via the World Wide Web.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Western Australia, 2007.

Thesis (M.S.)--University of Michigan, 1986.

Thesis (M.S.)--University of Michigan, 1986.