Historically, the primary belief has been that asthma is an atopic disease with the strongest risk factor for developing asthma being exposure to an allergen. However, researchers have begun to question that long held belief and are beginning to study other postnatal environmental factors such as stress. Research delving into maternal postnatal distress and the subsequent effects seen upon the developing neonatal immune system as it pertains to asthma has gained momentum. With that in mind, the focus of this research was 1) to determine if skin infections are more likely to be seen in young children who have been exposed to maternal distress, 2) to determine if skin infections in children from infancy to age 2 are associated with asthma, independent of atopic dermatitis, and 3) to determine if the association between early life skin infection and asthma was independent of recent stress biomarkers such as cortisol and dehydroepiandrostrone (DHEA). To meet the objectives listed above, the 1995 SAGE (Study of Asthma, Genes and the Environment) Manitoba birth cohort of 13980 children was used. Maternal postnatal distress, skin infection and atopic dermatitis in the infant, asthma at age 11 and other risk factors for asthma were derived from Manitoba’s health care databases. For objective 3, data on stress biomarkers (Cortisol/DHEA ratio) were obtained from the SAGE nested case-control study. Multivariable logistic regression analysis confirmed the first objective that skin infections (adj. OR 1.25, 95% CI 1.13-1.39) and or atopic dermatitis (adj. OR 1.46, 95% CI 1.26-1.70) seen in children from birth to age 2 could be used as indirect markers of stress. The second objective determined that children who exhibited an early skin infection, from birth to age two, were at an increased risk for developing asthma by age 11 independent of atopic dermatitis. However, this finding was dependent upon frequency of health care use. Those children that exhibited an early skin infection and had less than 24 health care visits over 7 years were 1.33 times (95% CI 1.01-1.75) more likely to acquire asthma by age 11 than those who did not have an early skin infection. Children with fewer health care visits were 1.44 times more likely to have asthma. The third objective was not met because the association between early skin infection and asthma was not independent of the Cortisol/DHEA ratio. However, the univariate results for skin infection in the nested case-control study were not significant. The findings of this thesis may be used by family physicians or paediatricians when looking for tangible markers that may indicate infants at risk for developing asthma by school age.

Background and Rationale: Asthma and overweight are public health concerns. Lifestyle, including dietary and activity patterns, is associated with overweight and asthma. Moreover, an association between these two diseases has been described. Yet, few studies have considered these associations longitudinally in youth. Methods: Based on data from the 1995 Manitoba Birth Prospective Cohort (n=723, 404 [55.9%] boys), we designed a series of studies to address the question: “Do obesity and related lifestyle behaviours influence asthma and airway hyperresponsivess (AHR) outcomes in children?” Following protocol for a mixed methods sequential explanatory design study, we first considered this research question using quantitative methods. Exposure variables included weight status (body mass index (BMI); BMI z-scores; normal weight vs. overweight), diet, physical activity and screen time. Outcome variables included asthma and AHR at 8-10 years old and at 12-13 years old. Quantitative findings provided direction for the qualitative investigations. That is, we sought to further explain some of the quantitative findings using qualitative methods. For the qualitative portion of this dissertation, 15-16 year old youth were purposively selected (Winnipeg residency, asthma status, gender) from the 1995 Manitoba Prospective Birth Cohort. Due to recruitment challenges, participation was supplemented with youth from the Canadian Asthma Primary Prevention Study, using the same purposive selection criteria. Quantitative Results: Overweight at 12-13 years old was associated with a two-fold increased odds of persistent asthma in girls. In contrast, boys within the highest BMI quartile at 8-10 years old were nearly twice as likely to have remittent asthma at 12-13 years old. High vegetable intake was protective against allergic asthma and moderate-to-severe AHR by 50% and 42%, respectively. High screen time at 8-10 years old, particularly amongst overweight youth, was associated with an increased odds of asthma, but not AHR at 8-10 years and 12-13 years; there were no associations between physical activity, asthma and AHR. Qualitative Results: Youth spoke of asthma as a condition that neither limits physical activity, nor is an excuse for refraining from physical activity. Conclusions: Modest evidence that some quantitatively-measured weight and related lifestyle behaviours during the pubertal years is associated with asthma. Yet, qualitative data suggest that youth with asthma believe that physical activity is achievable despite their condition, although some describe that asthma interferes with physical activity.

No description available.

No description available.

No description available.

No description available.

Thesis (MSocSc)--University of South Australia, 1995

[Truncated abstract] Asthma is a chronic and complex disorder and despite our increase in the understanding of the genetics, pathology and mechanisms underlying asthma a gold standard definition of asthma does not exist. A criterion for recognising and diagnosing asthma in epidemiological studies is crucial in order to determine risk factors for disease. Prospective longitudinal birth cohort studies have increased our understanding of the natural history and risk factors for asthma, yet we are still not able to accurately predict which children will go on to have asthma as adults. It is during the transition from childhood to adolescence where factors underlying asthma change and the prevalence of asthma shifts between the sexes. There are inconsistencies regarding risk factors for the development and persistence of disease during this transitional period. Risk factors predicting the development and persistence of asthma and intermediate phenotypes (BHR, airway inflammation and atopy) may be influenced by gender and risk factors predicting disease may differ between childhood and adolescence. Aims 1. To identify risk factors for Asthma, BHR and Atopy at 14yrs of age. 2. To determine risk factors for persistence of asthma between 6 and 14 years. 3. To examine the influence of gender on risk factors during adolescence. Method The West Australian Pregnancy Cohort is a longitudinal birth cohort. The cohort initially consisted of 2868 live births with follow-ups at 1, 2, 3, 6, 8, 10 and 14 years of V age. ... Strong associations were seen with BHR and new diagnosis of wheeze and asthma in VI teenagers. Interestingly having either a cat or dog inside was protective for persistence of disease; in particular stronger associations were seen in teenage girls not in boys. During this transitional period the risk factors for asthma and intermediate phenotypes differ between the sexes. Different mechanisms are likely to be involved in determining asthma in boys and girls during adolescence and shed new light on the recognised switch in the gender balance in asthma prevalence from the male predominance in childhood to the female predominance in adult life. Our understanding of the natural course of disease from the prenatal period to adulthood and the identification of the various asthma phenotypes has the potential to change prognosis and planning of therapeutic strategies. Identifying those at high risk for persistence of disease in the early stages of life will allow therapeutic interventions to be more appropriately targeted.

Research Doctorate - Doctor of Philosophy (PhD) / In Western society, increased asthma prevalence over recent years has coincided with changes in dietary patterns, leading to the hypothesis that a Western diet increases susceptibility to asthma. Components of the diet that may be important are antioxidants (e.g. lycopene) and fatty acids. Lycopene and long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects. As asthma is a disease linked to oxidative stress and inflammation, it was hypothesised that these nutrients may have a beneficial effect individually, and may have a synergistic anti-inflammatory effect when used in combination. The aim was to examine the ability of lycopene and/or LCn-3PUFAs to protect against virus-induced inflammation, as rhinovirus infection is the primary cause of asthma exacerbation. The results presented demonstrate that both lycopene and DHA (but not EPA) individually decreased the inflammatory response of airway epithelial cells infected with rhinovirus. The results also showed that DHA supplementation increased the utilization of lycopene by cells. Furthermore, lycopene reduced rhinovirus replication. A combination of lycopene and DHA also reduced the inflammatory response of cells to rhinovirus infection, however, no synergistic anti-inflammatory effect was apparent. It is concluded that consumption of foods containing lycopene and DHA may exhibit a beneficial effect on the inflammatory response to rhinovirus infection. This may have important clinical implications, as increased dietary intake of foods rich in these nutrients may lead to a reduction in the frequency and severity of asthma exacerbations.

Research Doctorate - Doctor of Philosophy (PhD) / Asthma involves chronic inflammation of the airways that is heterogeneous in nature. Eosinophilic airway responses are well described in asthma, however non-eosinophilic subtypes of asthma have been recently reported, and can involve the influx of neutrophils into the airways (neutrophilic asthma). Neutrophils are important effector cells of the innate immune system. These cells are the first to migrate to inflammatory sites, where they contain and eliminate pathogenic microorganisms. Neutrophils also release cytokines and chemokines that initiate and amplify inflammatory responses. The mechanisms of neutrophilic asthma remain largely unknown; however activation of the innate immune response is implicated, particularly increased levels of proinflammatory cytokines Interleukin (IL)-8 and IL-1beta and gene expression of Toll Like Receptor (TLR)-4 and TLR2 have been demonstrated in induced sputum samples. This thesis examines innate immune responses of airway and circulating neutrophils, with a focus on neutrophilic asthma. Innate immune neutrophil activation occurs in response to exposure to Lipopolysaccharide (LPS), which activates TLR4. The activation response consists of the release of preformed granule associated mediators such as Matrix Metalloproteinase (MMP)-9 and Oncostatin M (OSM), new gene transcription and release of inflammatory cytokines such as IL-8, IL-1beta and Tumor Necrosis Factor (TNF)-alpha, and new gene transcription of TLR2 & TLR4 which serve to amplify neutrophil responses. In addition, this thesis examines whole genome gene expression profiles of circulating neutrophils in neutrophilic and eosinophilic asthma. The aims of this thesis are based on the hypothesis that dysregulation of innate immune neutrophil responses occurs with ageing and airway disease, particularly neutrophilic asthma and chronic obstructive pulmonary disease (COPD). With advancing age, there were alterations in the innate immune responses of neutrophils, which were characterised by enhanced spontaneous activation of both airway and circulating neutrophils, and a decreased response of circulating neutrophils to LPS. There was a decreased activation of airway neutrophils in airway disease that was most pronounced in neutrophilic asthma and COPD, with decreased production and release of proinflammatory cytokines most likely due to a downregulation of TLR4. TLR2 was downregulated in resting and LPS stimulated circulating neutrophils in asthma, particularly neutrophilic asthma. Circulating neutrophils had a decreased spontaneous release of total MMP-9, and downregulation of OSM, TLR2 and TLR4 at rest in COPD. However when stimulated with LPS, subjects with COPD had an enhanced proinflammatory cytokine release, with increases in IL-8 and TNF-alpha compared to subjects with asthma or healthy controls. Analysis of whole genome gene expression of circulating neutrophils in asthma revealed distinct gene profiles relating to asthma subtype. There was upregulation of genes relating to cell motility, inhibition of apoptosis and the NF-kB in neutrophilic asthma, which would contribute to their accumulation in the airways. The innate immune response is critical in controlling infections by bacteria and viruses. The reduced innate immune response of airway neutrophils in airway disease could contribute to impaired local defense, which may lead to an increased susceptibility to infection by invading pathogens. Systemically, the molecular mechanisms of neutrophilic asthma are distinct from eosinophilic asthma and may involve the enhancement of neutrophil chemotaxis and survival, contributing to their accumulation in the airways.