Airway challenges in different clinical phenotypes and their relationship to markers of disease and treatment

  • Karine Leila Clearie

    Student thesis: Doctoral ThesisDoctor of Medicine


    Asthma is a chronic disease, which affects over 300 million people worldwide.Despite the introduction of both national and international guidelines, asthma control remains poor. The aim of this thesis is therefore to explore possible new strategies for improving the management of asthma. The first strategy to be explored is ‘titrating asthma treatment to suppress underlying airway inflammation’. The benefits of such a strategy have already been demonstrated,however, the lack of an adequate ‘inflammometer’ have limited its application to the research/ hospital setting. Mannitol challenge appears to be the most promising candidate, as it is portable and relatively cheap. The aim of the first study in this thesis is therefore to trial the use of mannitol challenge in a community setting. The selection of an appropriate ‘inflammometer’ is not limited to the clinical setting, it is equally important in research. This is particularly true when determining therapeutic equivalence between inhaled steroids. The aim of the second study in this thesis is therefore to determine which inflammatory outcomes demonstrate sufficient assay sensitivity, as part of a cross-over trial, to detect dose response effects on airway and systemic markers The second strategy to be examined in this thesis is tailoring asthma therapy according to asthmatic phenotype. Two groups of asthmatics that differ significantly from traditional ‘inflammatory asthma’ have been selected. Asthmatic smokers are known to develop relative resistance to the beneficial effects of inhaled steroids. A recent post hoc analysis of the GOAL trial has suggested that smokers may gain greater benefit from the addition of a long-acting beta-2 agonist vs. doubling the dose of inhaled steroid. The third study in this thesis therefore aims to examine this in a prospective fashion. Another group of individuals in whom the traditional approach to asthma management and diagnosis may not be appropriate is elite athletes. In has been well documented that the mechanism of bronchospasm in athletes involves the drying/ cooling of airways. However, even within this category there are athletes to which this mechanism of action is unlikely to apply.Elite swimmers, for example, exercise in a warm, humidified environment. It therefore seems unlikely that tests designed to reproduce hyperosmolar shifts will have the same diagnostic sensitivity as they do in cold weather or track athletes. The aim of the fourth and fifth studies included in this thesis is therefore to compare various diagnostic tests in swimmers to determine which are the most sensitive.
    Date of Award2010
    Original languageEnglish
    SupervisorBrian Lipworth (Supervisor)


    • Asthma

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