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Title: Dietary supplementation for the treatment of hyperpnoea induced bronchoconstriction in physically active asthmatics
Author: Williams, N.
ISNI:       0000 0004 5920 7989
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2015
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Asthma is a significant public health burden with 5.4 million people in the UK currently receiving treatment for the condition. Exercise induced bronchoconstriction (EIB) is a term used to describe an acute asthmatic episode following exercise and is highly prevalent amongst asthma sufferers. Traditional treatment involves the use of pharmacological interventions, the long-term use of which can have significant side effects and reduced efficacy in athletic populations. The purpose of this thesis was to initially establish a reproducible means of measuring bronchoconstriction in asthmatics through an experimental model of EIB termed hyperpnoea induced bronchoconstriction (HIB), and then investigate the use of dietary supplements to treat HIB and suppress markers of airway inflammation. Accordingly this thesis investigated: (i) the test-retest reproducibility of the bronchoconstrictive response to eucapnic voluntary hyperpnoea in physically active asthmatics and non-asthmatics, (ii) the effects of omega 3 polyunsaturated fatty acid supplementation dose level (6.2 g·d-1 vs 3.1 g·d-1) on the severity of hyperpnoea induced bronchoconstriction, and (iii) the effects of prebiotic trans-galactooligosaccharide (B-GOS) supplementation on severity of hyperpnoea induced bronchoconstriction and inflammatory markers in physically active asthmatics. It was found that eucapnic voluntary hyperpnoea incorporating real-time visual feedback of minute ventilation V̇E) and end-tidal PCO2 yielded a smallest meaningful change of 88 mL highlighting a highly reproducible bronchoconstrictive response over both short- term (21 days) and long-term (70 days) periods, in physically active asthmatics with HIB. No between-day differences in the bronchoconstrictive response as measured by both absolute drop in forced expiratory volume in one second (FEV1, mL) and the percentage change in FEV1 (%ΔFEV1) following the eucapnic voluntary hyperpnoea protocol in the asthmatic participants were evident. Subsequently EVH was deemed a suitable technique for monitoring the effectiveness of treatment interventions. This thesis shows for the first time that lower doses of ω3-PUFA (3.1 g·d-1) are equally as effective as higher doses (6.2 g·d-1) in reducing the severity of hyperpnoea induced bronchoconstriction in recreational athletes. Maximum reductions in FEV1 at day 0 of 28 ± 87%, and -27 ± 17%, had improved to -19 ± 15%; and -18 ± 14% for the 6.2 g·d-1 and 3.1 g·d-1 ω3-PUFA interventions respectively. Both ω3-PUFA interventions resulted in equal reductions of up to 30% in resting levels of exhaled nitric oxide, and equal suppression up to 44% in inflammatory maker urinary 9α, 11β-PGF2 concentration following the eucapnic voluntary hyperpnoea challenge. These data highlight that lower ω3-PUFA doses represent a potentially beneficial treatment for physically active asthmatics suffering with HIB whilst reducing the burden of cost, compliance and potential for gastrointestinal distress. A highly novel finding of this thesis was that a 21 day intervention of a prebiotic galactooligosaccharide (B-GOS) markedly improved the severity of bronchoconstriction in HIB participants, with %ΔFEV1 improving by up to ~40%. This occurred in conjunction with reduced markers of airway inflammation including serum concentrations of TNF-α (reduced by 36%), CCL17 (reduced by 22%), and C-reactive protein (reduced by 11%) in the HIB participants. For the first time this suggests that favourable manipulation of the commensal bacteria within the gut by B-GOS will influence immune regulation and inflammatory responses and could prove to be a novel therapeutic target for asthma and HIB. It is attractive to speculate that combinations of ω3-PUFA, prebiotics, and probiotics could prove to be novel therapies for a range of asthma phenotypes and other respiratory diseases. Furthermore there is scope to develop a greater understanding into the mechanisms behind the effectiveness of the gut microflora as a therapeutic treatment option for inflammatory airway diseases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available