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Title: Anti-inflammatory therapy in allergic airways disease
Author: Wilson, Andrew M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The system adverse effects of inhaled corticosteroids were investigated in dose-response studies. By measuring cortisol suppression, it was shown that a more potent inhaled corticosteroid (fluticasone propionate (FP)) exhibits greater systemic bioactivity (2-fold at highest licensed doses) than a weaker steroid (triamcinolone acetonide (TAA)). No differences were detected between inhaled corticosteroids of similar potency (TAA and flunisolide), even when using sensitive and novel measures e.g. low dose ACTH stimulation and early morning urine cortisol excretion. The latter test may prove to have clinical implications for monitoring patients, as it was shown to be more sensitive than dynamic or basal serum cortisol measures. However, the lung delivery of a corticosteroid has a greater effect on systematic bioactivity than its dose or potency, as the systematic activity of FP via two different inhaler devices was shown to vary more than 4-fold. Studies comparing oral prednisolone with inhaled FP, showed FP to exhibit dose-related suppression of serum cortisol in a 1:8.5mg ratio compared to prednisolone. Interestingly, the effects of FP on markers of bone metabolism were less marked than adrenal suppression, compared to the effects of prednisolone. Intra-nasal FP also produced significant urinary cortisol suppression, whereas other intra-nasal corticosteroids (TAA, budesonide (BUD), beclomethasone, mometasone) had no significant effects on 24 hour cortisol, bone or blood markers. Furthermore, the addition of intranasal to inhaled FP resulted in more patients with sub-normal cortisol values. A meta-analysis of all dose-response studies assessing different inhaled corticosteroids was also performed with results supporting this data. When assessing therapeutic effects of inhaled corticosteroids, it was shown that a lower dose of BUD was required to optimise symptoms, lung function and exhaled nitric oxide (eNO), compared to other measures of inflammation; serum markers (ECP), and bronchial hyperreactivity to adenosine monophosphate (AMP) and methacholine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available