Paediatrics (RCH) - Theses

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    The epidemiology and risk factors of anaphylaxis and food-induced anaphylaxis worldwide
    Wang, Yichao ( 2019)
    Anaphylaxis is a severe allergic reaction that is rapid in onset and may cause death. There are increasing reports from individual countries and regions on anaphylaxis prevalence or incidence; however, there has been no systematic summary of the worldwide evidence among the paediatric population. An increasing rate of hospital admissions for food-induced anaphylaxis was observed in Australia from 1993 to 2012, especially among young children. Although rising rates of anaphylaxis have also been reported in other western countries, little is known about the time trends in Asian regions. Time trends of adrenaline auto-injectors (AAI) prescription is a good supplement surrogate for the time trends of anaphylaxis risk in the community. Some studies reported time trends of AAI prescription internationally, such as USA, UK and Canada; however, there is little information on the time trends of AAI prescription or dispensing in Australia in recent years. Previous international studies have reported that ethnicity is associated with the risk of anaphylaxis. Food allergy was found to be more common in children born in Australia with Asian parents than children born in Australia with Caucasian parents. However, it is not known whether ethnicity is also a risk factor for the development of anaphylaxis and food-induced anaphylaxis in Australia. Food allergy is an important cause of anaphylaxis. People with food allergy have a high risk of anaphylaxis, but not all of them will have an anaphylactic reaction. It is hence crucial to know the risk factors of having anaphylactic reactions in the food allergic population. Few studies have examined risk factors for food-induced anaphylaxis in food-allergic children. The characteristics of children with food allergy who are more likely to experience anaphylaxis are unknown. Therefore, this thesis aims to describe the worldwide incidence and prevalence of anaphylaxis and identify risk factors for anaphylaxis and food-induced anaphylaxis in both the general population and the food-allergic population. Firstly, I conducted a systematic review to describe the incidence and prevalence of anaphylaxis in children worldwide. I found a high heterogeneity between studies which limited the interpretation of an overall combined incidence and prevalence. I found increasing time trends of all-cause anaphylaxis and food-induced anaphylaxis in children from included studies and studies in developing areas were underrepresented. By using hospital admission data for anaphylaxis from the Hospital Authority of Hong Kong, I reported increasing time trends of both all-cause anaphylaxis and food-induced anaphylaxis in the paediatric population in Hong Kong between 2001 and 2015. By analysing AAI dispensing data from the Australian Pharmaceutical Benefits Scheme (PBS) database, I found an increasing incidence rate of patients with AAI in Australia from 2005 to 2014. Different trends were reported by sex, age and state. I found a shift towards more AAI prescriptions being provided by general practitioners (GPs) rather than specialists in most regions in Australia. By using the data from the School Entrant Health Questionnaire in Victoria, Australia, I investigated the risk factors of anaphylaxis in the general population. I found an association between Asian ethnicity and anaphylaxis risk in children living in Australia and identified the high-risk group (Australian-born children with Asian-born mothers) for anaphylaxis. Lastly, I used data from the HealthNuts study to explore the frequency and risk factors of anaphylaxis in food allergic children from a community setting. I found a high frequency of experiencing anaphylactic reactions (11.5%) in the preceding 12 months in children with food allergy. In summary, the results presented in this thesis have provided further knowledge on the epidemiology of anaphylaxis and food-induced anaphylaxis in the general population and identified important predictors of anaphylaxis in the general population and the food allergic population. The identification of these essential predictors has important implications for the management of anaphylaxis and will improve our understanding of the development of anaphylaxis.
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    Environmental and genetic risk factors for food allergy in children with Asian ancestry
    Suaini, Noor Hidayatul Aini Bte ( 2019)
    Epidemiological and genetic studies on food allergy to date have focused primarily on the Caucasian population. This is despite emerging evidence that food allergy appears to be rising in Asian countries, alongside the increasing Westernisation and urbanisation in these countries. Even less is known about Asian migrants living in Western countries. A population-based study on food allergy found the risk of food allergy to be three times higher in infants of East Asian ancestry than infants of Caucasian ancestry. It is thought that infants growing up in Australia are exposed to environmental agents that have a differential effect on the immune system depending on their genetic background. However, the influence of specific genetic and environmental risk factors is currently unknown. It is also unclear if the increased risk of food allergy translates to higher risk of other allergic diseases later in childhood. The main objective of this thesis is to identify specific environmental and genetic factors on the risk of food allergy in the Asian population living in Australia. This thesis aims to quantify the prevalence of, and identify risk factors for food allergy and allergic comorbidities in the Asian population. An additional aim is to identify genetic variants that increase the risk of food allergy in the East Asian population and compare this to the Caucasian population living in Australia. This thesis primarily used data and samples from the longitudinal HealthNuts study where 5,276 1-year-old infants attending council run vaccination sessions across Melbourne were recruited. Skin prick tests to a range of food were carried out on infants and those with a wheal size less than 1 mm underwent an oral food challenge. The 1-year-old infants were followed up again at age 6 years and data collected at this follow-up visit were also used for analyses in this thesis. Additionally, data collected from a Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort was also used to compare the risk factors and prevalence of allergic diseases between East Asians living in Melbourne and East Asians living in Singapore. This thesis reports that Australian-born children with East Asian parents have a higher burden of allergic rhinitis, eczema and aeroallergen sensitisation but not asthma, in the first six years of life compared to children of Caucasian ancestry. Moreover, children with IgE-mediated food allergy and eczema in infancy were 3 times more likely to have asthma and 2 times more likely to have allergic rhinitis at age 6 years, irrespective of ancestry. Additionally, East Asian children living in Melbourne have a higher risk of food allergy compared to East Asian children living in Singapore. Despite delayed introduction of allergens into the diet compared to the Asian population in Melbourne, Asian children in Singapore had less food allergy. While eczema rates were lower in Singapore than in Melbourne, early onset eczema was associated with an increased risk of food allergy in both Singapore and Melbourne. In terms of genetic risk factors, a systematic review conducted as part of this thesis identified several genes of interest known to be involved in immune regulation, cell function and epidermal barrier function. However, studies were of varied quality and the reproducibility of findings for the same SNPs were minimal. Some of the highly re-producible genes identified from the literature include HLA, FLG and IL13. Additionally, there was also a paucity of studies carried out in the Asian population that were able to elucidate underlying mechanisms for the differential food allergy risks observed in the population. This highlighted the need for genetic studies focused in this population. This thesis found that HLA rs7192 minor allele was associated with increased risk of peanut allergy in the Caucasian population but not East Asian population. Among sensitised children with two East Asian born parents, those with the minor allele for rs231735, rs231804 or rs11571291 (all CTLA4) have a reduced risk of egg allergy. The findings of this thesis identify Asian children living in Australia as a high risk allergic group not just in infancy but throughout early childhood. As a multifactorial disease, both environmental and genetic factors are known to contribute to the pathogenesis of food allergy. Therefore, it may be that the increased risk of food allergy observed in genetically predisposed East Asian children living in Melbourne unmasked upon exposure to environmental risk factors.