Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501189
Title: Nasal and whole blood challenge models for allergic rhinitis and COPD
Author: Neighbour, Helen
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2009
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Abstract:
Nasal allergen challenge (NAC) is a non-invasive model to study the mechanism of allergic rhinitis and effects of novel anti-inflammatory therapies. The repeatability and dose response of a single NAC was studied, followed by development of a daily repeat NAC model involving 4 challenges on consecutive days. However, the results of earlier published work could not be reproduced, since in nasal filter paper (FILT P) eluate in both studies there were no significant changes in levels of interleukin (IL)-4, IL-5 and IL-13. However the daily repeat NAC model did cause priming in terms of symptoms, eosinophils, and nasal lavage IL-5 and IL-13. Proposals were made for implementation of a synthetic absorptive matrix (SAM) as an alternative to Whatman's FILT P and also to deliver higher doses of allergen to the nose. Using SAM resulted in high serial levels of IL-4, IL-5 and IL-13 being detected in SAM eluates during the late phase after NAC (appendix). In cigarette smokers I requested subjects to exhale cigarette smoke through their noses, to provide a nasal cigarette smoke challenge method. FILT P is likely to distort detected levels of mediators in nasal secretions, but in FILT P eluates there were statistically significant elevations of IL-8 (p=0.01) and IL- 12p70 (p=0.02) at baseline in Chronic Obstructive Pulmonary Diseae (COPD) patients. However there were increases in nasal lavage MCP-1 at 8h in COPD patients and healthy controls following cigarette smoke (p=0.02). A cigarette smoke conditioned medium (CSCM) was employed to stimulate whole blood upregulation of CD11 b measured by flow cytometry on leukocytes. CSCM caused upregulation of neutrophil CD11 b, but this could not be inhibited by anti-oxidants. In contrast, menadione (MQ) stimulates intracellular generation of oxidants, and this caused neutrophil CD11 b upregulation that was inhibited by glutathione. Xanthine with xanthine oxidase (X+XO) generates an extracellular source of oxidants, and this caused an increase in neutrophil CD11 b on washed blood cells, that could also be inhibited by glutathione. NAC or cigarette smoke nasal challenge, as well as stimulation of human whole blood with oxidants, have potential as challenge models - but SAM should be used instead of FILT P.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.501189  DOI: Not available
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