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Title: Infection, inflammation & innate immunity in the paediatric CF airway
Author: Thursfield, Rebecca Marie
ISNI:       0000 0004 6059 2757
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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This thesis focuses on infection and immunity within the airways in cystic fibrosis (CF), particularly the role of the antimicrobial peptides (part of the innate immune system) and their relationship to vitamin D status. Vitamin D response elements have been identified in the genes encoding the antimicrobial peptides cathelicidin (LL37) and human β defensins (HBD-2) and in-vitro vitamin D significantly induces expression of these peptides in both CF and non-CF bronchial epithelial cells. As innate defence is pivotal to airway health and is one of the proposed ways that vitamin D deficiency contributes to worsening respiratory health, this thesis will consider first immunity of the normal airway and the interactions with vitamin D and then discuss the pathophysiology of CF and the role of vitamin D on the innate immune system within CF. The role of vitamin D on infection and inflammation in the airways of infants with CF is explored and the impact of Vitamin D levels seen immunologically and functionally over the first year of life is described. Finally the role of vitamin D as an immunomodulatory molecule is explored in a greater range of CF disease severity and age. Through the various parameters explored, in different CF patient populations, the conclusion remains the same; vitamin D deficiency is not associated with increased infection, greater inflammation nor a worse clinical outcome. The possible reasons for the lack of any relationship are discussed in the final chapter; either a missed signal because the levels studied were on the low or high flat parts of a 2 sigmoid relationship thus effects seen only in really severe deficiency or because supra-high levels are needed to see any effect, the effect being lost in the inflammation seen within the CF airway or a true lack of relationship.
Supervisor: Davies, Jane ; Bush, Andrew ; Alton, Eric Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral