Wong, Yun Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 142-162). / Abstracts in English and Chinese. / Abstract (in English) --- p.ii / Abstract (in Chinese) --- p.vi / Acknowledgement --- p.ix / Statement of Work --- p.x / Table of Contents --- p.xi / List of Tables --- p.xiv / List of Figures --- p.xvi / Glossary of Terms and Abbreviations --- p.xviii / Chapter Section I: --- Introduction --- p.1 / Chapter Chapter 1: --- General Overview of Asthma --- p.2 / Chapter 1.1 --- Asthma definition and its phenotype --- p.2 / Chapter 1.2 --- Asthma epidemiology and its prevalence in past decades --- p.4 / Chapter 1.3 --- Hygiene hypothesis and asthma development --- p.8 / Chapter 1.4 --- Asthma pathogenesis and innate immunity --- p.12 / Chapter 1.5 --- The environmental factors and genetic makeup in relation with asthma --- p.17 / Chapter Chapter 2: --- Study Plan and Obj ective --- p.21 / Chapter Section II: --- Literature Review --- p.24 / Chapter Chapter 3: --- Indoor Environmental factors of Asthma --- p.25 / Chapter 3.1 --- Overview of the indoor environmental factors --- p.25 / Chapter 3.2 --- House dust endotoxin --- p.27 / Chapter 3.2.1 --- Determinants of endotoxin exposure in home environment --- p.21 / Chapter 3.2.2 --- Protective role of endotoxin in allergy and asthma development --- p.29 / Chapter 3.2.3 --- Deleterious effect of endotoxin exposure in asthma: the dark side --- p.31 / Chapter 3.3 --- Allergen --- p.34 / Chapter 3.3.1 --- Allergens: an update --- p.34 / Chapter 3.3.2 --- Determinants of allergens in home environment --- p.35 / Chapter 3.3.3 --- Allergens avoidance: environmental intervention --- p.36 / Chapter 3.4 --- Nitrogen dioxide --- p.40 / Chapter 3.4.1 --- Determinants of indoor nitrogen dioxide and its relation with gas cooking --- p.40 / Chapter 3.4.2 --- The adverse effects of nitrogen dioxide on respiratory symptoms --- p.41 / Chapter 3.4.3 --- Reactive nitrogen species and nitrosative stress in asthma --- p.42 / Chapter Chapter 4: --- CD14 Single Nucleotide Polymorphisms and Asthma --- p.45 / Chapter 4.1 --- Overview of CD14 receptor --- p.45 / Chapter 4.2 --- Action of CD14 receptor in endotoxin response --- p.47 / Chapter 4.3 --- Relation of CD14 with asthma --- p.48 / Chapter 4.3.1 --- Associations between CD14 polymorphisms and asthma phenotypes --- p.48 / Chapter 4.3.2 --- Endotoxin switch concept: from gene to gene - environment --- p.52 / Chapter Section III: --- Study Core --- p.55 / Chapter Chapter 5: --- Methodology in indoor environment investigation and its result --- p.57 / Chapter 5.1 --- Study Population --- p.57 / Chapter 5.2 --- Home Visiting Protocol --- p.60 / Chapter 5.2.1 --- The International Study of Asthma and Allergies in Childhood (ISAAC) --- p.60 / Chapter 5.2.2 --- ISAAC questionnaire --- p.61 / Chapter 5.2.3 --- House dust collection procedures --- p.62 / Chapter 5.2.4 --- Indoor nitrogen dioxide measurements --- p.65 / Chapter 5.2.4.1 --- Ogawa passive sampler --- p.65 / Chapter 5.2.4.2 --- Preparation and measurement procedures --- p.66 / Chapter 5.2.4.3 --- Indoor nitrogen dioxide quantification --- p.67 / Chapter 5.3 --- House dust extraction --- p.69 / Chapter 5.4 --- House dust endotoxin measurement --- p.70 / Chapter 5.5 --- Allergen measurement --- p.72 / Chapter 5.6 --- Statistical Analysis --- p.75 / Chapter 5.7 --- Results --- p.77 / Chapter 5.7.1 --- Demographic data and subjects characteristics --- p.77 / Chapter 5.7.2 --- "Dust weight, endotoxin and allergen levels and their determinants in household" --- p.82 / Chapter 5.7.3 --- Indoor NO〕2levels and its determinant in household --- p.95 / Chapter 5.7.4 --- Associations between indoor environmental factors and respiratory health --- p.96 / Chapter 5.7.4.1 --- Clinical symptoms --- p.96 / Chapter 5.7.4.2 --- Exhaled NO levels --- p.101 / Chapter 5.7.4.3 --- Spirometric indices --- p.103 / Chapter Chapter 6： --- Methodology in genotyping CD14 polymorphisms and its result --- p.105 / Chapter 6.1 --- Study population --- p.105 / Chapter 6.2 --- Serum Total and allergen-specific IgE measurement --- p.106 / Chapter 6.3 --- CD14 Genotyping s --- p.107 / Chapter 6.3.1 --- Genotyping promoter SNPs ofCD14/-159 and -1359 --- p.107 / Chapter 6.3.2 --- Genotyping promoter SNP of CD14/-1619 --- p.109 / Chapter 6.3.3 --- Validation of genotyping by sequencing --- p.111 / Chapter 6.4 --- Statistical Analysis --- p.112 / Chapter 6.5 --- Results --- p.113 / Chapter 6.5.1 --- Subjects characteristics and clinical features. --- p.113 / Chapter 6.5.2 --- Associations between CD14 SNPs and asthma phenotypes --- p.114 / Chapter Chapter 7: --- Discussion --- p.120 / Chapter 7.1 --- Influence of indoor factors on asthmatic children --- p.120 / Chapter 7.2 --- CD14 polymorphisms in modifying asthma phenotypes --- p.135 / Chapter Chapter 8: --- Conclusion and Further Works --- p.138 / References --- p.141 / Appendix 1 Questionnaire / Appendix 2 Publications

[Truncated abstract] Asthma genetic studies have identified many genes that contribute to the pathogenesis of asthma and related variables. Members of the secretoglobin family appear to play an important role in controlling airway inflammation but they have received relatively little attention in asthma genetic research. In this thesis, I have investigated the genes of two members of the secretoglobin family (16 kDa Clara cell secretory protein (CC16) and secretoglobin 3A2 (SCGB3A2)) that are expressed at high levels in the airways and are important anti-inflammatory agents. The overall aim of these studies was to investigate the genetic variability of the CC16 and SCGB3A2 genes and their influence on airway inflammatory disease. The main hypothesis was that genetic variability in the genes for CC16 and SCGB3A2 exert an influence on airway inflammatory disease. Three populations were investigated: (1) a paediatric case control population (n=99), (2) an unselected birth cohort followed longitudinally at ages 1 month (n=244), six (n=123) and 11 years (n=195) and (3) an unselected Aboriginal Australian population (n=251). The case-control population was screened for novel DNA sequence variants in the CC16 promoter and the SCGB3A2 5’UTR and exons. No novel sequence variants were identified in the CC16 promoter and two were identified in the SCGB3A2 5’UTR (G- 811A and G-205A). A single nucleotide polymorphism previously identified in the CC16 gene (A38G) and the two polymorphisms identified in the SCGB3A2 gene were genotyped in both unselected populations. Genotype/phenotype associations were identified with adjustment for potential confounders such as age, gender, height and maternal tobacco smoking, where appropriate. This was due to the contribution of these factors to the aetiology of asthma, atopy and related phenotypes. All three polymorphism frequencies were significantly different between these two ethnically diverse populations