Background: Asthma is characterized by chronic airway inflammation in which leukocytes are attracted into the inflamed airway under the influence of chemokines. Molecular studies and allergen bronchoprovocation suggested that chemokines such as thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), eotaxin and regulated upon activation normal T-cell expressed and secreted (RANTES) were involved in the airway responses to allergen exposure. / Conclusions: Chemokines are important mediators in the pathophysiology of asthma and atopy. TARC in plasma and MDC in EBC appear to be useful biomarkers for assessing childhood asthma. Besides, MDC concentrations in UCB may predict the susceptibility to develop wheezing during infancy. / Methods: Asthmatic patients, non-allergic controls and healthy singleton newborns were recruited from attendants of a university teaching hospital. Atopy-related chemokines in peripheral blood and EBC were measured by enzyme-linked immunosorbent assays. Genomic DNA from asthmatics and controls was genotyped by restriction fragment length polymorphism to characterize single nucleotide polymorphisms (SNPs) in the genes encoding TARC, RANTES, interleukin-13 and CD14. / Objectives: This thesis investigated the relation between chemokines and asthma and atopy by: (a) measuring their concentrations in peripheral blood and exhaled breath condensate (EBC); (b) performing case-control association studies for genes encoding atopy-related chemokines and related molecules; and (c) analyzing chemokines in umbilical cord blood (UCB) in relation to wheezing phenotypes during infancy. / Results: Plasma TARC concentrations were higher in children with chronic asthma than controls, and also correlated with plasma total IgE. Among children with asthmatic exacerbation, plasma TARC concentrations showed inverse correlation with peak expiratory flow rates at presentation. When measured in EBC, MDC but not TARC or eotaxin was higher in asthmatics than controls. In our genetic association studies, SNPs in IL13, RANTES and TARC were associated with serum total and/or allergen-specific IgE. TARC C-431T was also linked to peripheral eosinophilia. However, none of these polymorphisms was associated with physician-diagnosed asthma. Interestingly, C-159T in CD14 was also associated with serum total IgE, but only among atopic asthmatic children. In the last part involving 124 singleton healthy newborns, MDC concentrations in UCB were significantly increased in newborns who wheezed during infancy. / Leung Ting-fan. / Adviser: Gary W.K. Wong. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (M.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 196-231). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344725 |
Date | January 2004 |
Contributors | Leung, Ting-fan., Chinese University of Hong Kong Graduate School. Division of Medicine. |
Source Sets | The Chinese University of Hong Kong |
Language | English |
Detected Language | English |
Type | Text, theses |
Format | electronic resource, microform, microfiche, 1 online resource (2, 338 leaves : ill.) |
Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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