Thesis (Ph. D.)--University of Nevada, Reno, 2007. / "December, 2007." Includes bibliographical references (leaves 77-89). Online version available on the World Wide Web.

Thesis (M. P. H.)--University of Hong Kong, 2006. / Also available in print.

Thesis (Ph.D.)--University of Adelaide, Dept. of Psychiatry, 1998. / Includes bibliography (v. 2, leaves 80-93).

Thesis (Ph.D.)--University of Western Australia, 2007.

Thesis (M.A.)--West Virginia University, 2000. / Title from document title page. Document formatted into pages; contains viii, 123 p. Includes abstract. Includes bibliographical references (p. 63-68).

Thesis (M.P.H.)--University of Hong Kong, 2006.

Thesis (Ph. D.)--University of Texas at Dallas, 2007. / Includes vita. Includes bibliographical references (leaves 169-177)

Submitted in fulfillment of the requirements for the degree of Master of Technology: Health Sciences, Durban University of Technology, Durban, South Africa, 2013. / Several genes are associated with an increased susceptibility to respiratory diseases, including asthma, which may be exacerbated by ambient air pollution. These genes include the Tumour Necrosis Factor alpha (TNFα) gene and the Cluster of Differentiation 14 (CD14) gene A total of 104 schoolchildren from seven primary schools in a heavily industrialized region of south Durban participated in the study. For the purpose of this study, DNA was extracted from whole blood using the GENTRA Puregene kit. Genotyping for the TNF-308α G/A polymorphism was conducted using restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). The CD14 (-159) C/T genotype was determined using real time PCR and Taqman probes (Applied Biosystems). Multiple logistic models and Pearson’s chi-squared tests were used to evaluate the association between any asthma, BHR, atopy, persistent asthma and genotype. Covariate-adjusted generalised estimating equations (Martin et al.) with lags of 1-5 days were used to evaluate genotype effect modification of exposure-response. The TNF-308α variant A allele was quite common in the population, it was detected in more than forty percent of the population and with an allelic frequency of 0.24. Similarly almost 38% of the population carried the variant CD14 (-159) T allele, with an allelic frequency of 0.24. TNF-308α G/A and CD14 (-159) C/T polymorphisms were not associated significantly with asthma, and its related respiratory phenotypes. In addition there was no association detected between any of the gene polymorphisms and the levels of their respective cytokine proteins. Increased TNFα levels were associated with persistent asthma. On the other hand lower sCD14 levels were associated with atopy in children. There was a significant relationship between TNF- α levels and acute asthma (p=0.03) and sCD14 levels and atopy (p=0.04) GEE models showed that the TNF- 308-α A allele carriers had a greater deterioration of lung function post pollution exposure to SO2 (intraday variability FEV1 readings lag 2) β= 2.62, CI (0.51, 4.71) p= 0.02 and p (interaction=0.03). There was a statistically significant gene environment interaction with NO in individuals who were carriers of the TNF- A allele (Nadir of PF readings lag 2: β= -12.3, CI (-22.09, -2.51), p=0.01 p (interaction) =0.03.and 5 day average β= - 42.83, CI (-70.11,-15.55), p≤0.005 and p (interaction) =0.01). With analysis of the CD14 gene polymorphism gene environment interaction, adverse effects of SO2 were limited to individuals carrying the C allele of this polymorphism, β= - 1.50, CI (-0.36, 3.37), p=0.01, p (interaction) =0.01. Carriers of the T allele seemed to have a protective effect with NO2 and NO exposure. Intraday variability of FEV1 improved 5 days post exposure to NO2 β= -4.02, CI (-6.52,- 1.53), p=0, p (interact) =0.05. There was also improvement five days post exposure to NO β= -9.42, CI (-12.45, -6.03), p= p≤0.005, p (interact) ≤0.005 There was no association of co-inheritance of the 2 gene polymorphisms, CD14 (-159) C/T and TNF-308α G/A, and protein expression or respiratory phenotype. The GEE model results were consistent with modification of air pollutant-pulmonary function relationships by proinflammatory cytokine associated genotypes. Results indicate that genetic susceptibility combined with exposure to pollutants causes adverse respiratory effects. This study supports the importance of further investigation on these and other genotype variants involved in inflammation and respiratory linked phenotypes in larger cohorts. / M

Background: Wheezing disorders have increased worldwide. The respiratory epithelium plays an important role in the pathogenesis of wheeze. Nasal epithelial cells (NEC) are a valid surrogate for bronchial airway epithelial cells, are accessible and could be a valuable tool in translational epidemiological studies. A better understanding of this layer may decrease the burden of wheezing disorders. Objectives: To determine the feasibility of sampling and culturing NEC from children and adults with and without different wheezing conditions in epidemiological studies. To study NEC mediator release in these individuals following different environmental exposures. Methods: NEC were sampled from unsedated children and adults with and without a wheezing condition by brushing. NEC were cultured in media and also exposed to interleukin-1 (IL-1) & tumour necrosis factor alpha (TNF-), house dust mite (HDM) extract, lipopolysaccharide (LPS) and extracted tobacco smoke (ETS) for 24 hours. Resulting supernatants were analysed via Enzyme – linked immunosorbent assay (ELISA) and cytometric bead array (CBA) for mediator release. Results: 287 individuals including 164 children and 123 adults where phenotyped and brushed. 81 samples reached tertiary passage. Decreased release of vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein -1 (MCP-1) was observed in wheezing individuals when compared to healthy controls. These cytokines were increased in individuals with chronic obstructive pulmonary disease (COPD) relative to both asthmatic and healthy adults. Individuals with/without allergic rhinitis demonstrated different mediator release. Conclusions: It is feasible to obtain NEC in adults and children for both epidemiological and translational research, although the presence of allergic rhinitis may act as a potential confounder. Differences are present in adults and children with asthma compared to healthy controls. Contrasting differences between COPD and asthma suggest that these are different conditions.

This cross-sectional mixed-method study with a small sample of 62 mothers of children with asthma is a pilot evaluating a new brief online e-health intervention: The Asthma Knowledge Test for Parents (TAKT-40), with all true answers. The TAKT-40 was highly recommended (77.4%) by mothers to others parents with children with asthma. The sample had a mean number of children of 2.31, a mean age of 39.13, with 66.1% (n= 41) White, 24.2% Black, and 9.7% (n=6) Hispanic—with 88.7% living with a partner (n=55). The mean level of education was between Some College and Master’s degrees, with 61.3% employed (n=38) and a mean annual household income for between $100,000 and $199,999. The mean age for children was 9.06, with a mean of 7.51 years since the asthma diagnosis, with 98.4% (n=61) prescribed medication, and 80.6% (n=50) currently taking it. Suggestive of the TAKT-40 being a potential brief online intervention of value, paired t--tests showed: mother’s self-ratings for level of knowledge were higher after they had taken the TAKT-40 with all true answers when compared to self-ratings of knowledge before taking it; and, mother’s self-efficacy for taking care of their child with asthma and helping their child achieve asthma control was higher after they had taken the TAKT-40 when compared to self-ratings after taking it. While controlling for social desirability, backwards stepwise regression showed (1) a higher asthma knowledge (on the TAKT-40), was significantly predicted by: Higher annual household income; Lower number of children; Greater extent of negative impacts from asthma on child, parent, and family—30.0% of the variance predicted with this model. Secondly, backwards stepwise regression found (2) a high asthma self-efficacy (on the Scale 2-Asthma Self-efficacy) for the three key behaviors was significantly predicted by: Fewer Barriers to Child’s Health Care—with 60.0% of variance being predicted. Qualitative data supplemented the quantitative findings, supporting the resultant implications and recommendations.