Abstract
BackgroundThe global prevalence of food allergies has been increasing over the last few decades with up to 8-10% of children being affected worldwide depending on country. This thesis aims to look at clinical characteristics and patterns of biomarkers to better understand the natural resolution, persistence and development of new peanut, sesame, and egg allergies in children over time. It also looks at the health economic burden in terms of healthcare costs in atopic and non-atopic children.
Methods
This thesis used data from children seen on the EAT and EAT-On studies. Clinical history and characteristics, biomarkers including skin prick test (SPT), specific IgE (sIgE), sIgE to individual allergens and mast cell activation test (MAT) were collected from participants and compared between allergic and sensitised but not allergic children at 3-months, 1-year, 3-years, and 7-12-years old. Logistic regression analyses were performed to observe which biomarkers were predictive of having food allergy at 7-12- years and these were done for peanut, sesame, and egg separately. Predictive probability models were created to determine the likelihood of a child having persistent egg allergy or having new sesame allergy 19 at 7-12-years of age. A separate analysis was also performed looking at early peanut allergy in a combined 20 cohort of participants from the EAT, LEAP and PAS cohorts. A predictive model was also created to look at peanut allergy resolution in early childhood. For the health economic analyses, a health economics questionnaire (HEQ) was developed to collect data on the utilisation and cost of healthcare services and comparing this between atopic and non-atopic children in the EAT-On cohort only.
Results
A total of 947 participants were included in the main analyses of the EAT-On study out of the original 1303 participants recruited for the EAT study. When looking at peanut allergy, an additional analysis was performed on a cohort of 2137 children of which 1168 were from the EAT study, 628 from the LEAP study and 177 came from the PAS cohort, who were part of the original cohort screened for participation in the LEAP study. In the EAT and EAT-On cohorts, the rates of atopic dermatitis remained relatively stable across time with approximately 20% of the cohort having AD at any time point. The prevalence rate of food allergies on the EAT-On study was 4.4% with a 4.3% prevalence rate if looking at allergies to at least one of the 3 foods (peanut, sesame, and egg) studied in this thesis. The prevalence rate of peanut allergy was 2.3%, sesame seed allergy was 1.5% and egg allergy was 1.5%. In terms of the natural history of allergies, within the EAT-On cohort there was very little peanut allergy resolution from 3-years to 7-12-years of age. However, in the separate analysis of the data from LEAP, EAT and PAS studies, which focussed on early peanut allergy development (i.e. peanut allergy developing before 12-months of age) and resolution (i.e. 14 resolving by 3-5-years of age), there was a resolution rate of 32.1%. This suggests that peanut allergy resolution likely occurs much earlier in childhood and older children are less likely to outgrow it. There were very few children who developed new onset peanut allergy or had peanut allergy resolution between 3-years and 7-12-years of age. With egg allergy, the prevalence rate decreased from 4.5% between 1-3-years of age to 1.5% at 7-12-years of age. All the children who were still allergic in later childhood had persistence of their egg allergy as there were no new cases of egg allergy that developed between 3 and 7-12-years of age. The rate of egg allergy resolution was 67.4% although not all children who were previously egg allergic returned for review. Surprisingly, sesame allergy increased in prevalence from 0.5% at 1-3-years of age to 1.5% at 7-12-years of age. Of the sesame allergic children at 7-12-years of age, 71.4% had new onset sesame allergy that developed after 3-years of age.
Biomarkers, including mast cell activation tests (MAT), were utilised to study each food individually. Peanut SPT, peanut-sIgE, Ara h 2-sIgE and MAT to peanut were all significantly higher in the peanut allergic children compared to the peanut sensitised but not allergic children. A predictive model for peanut allergy resolution associated having lower peanut-sIgE and peanut SPT, in addition to not having egg allergy or atopic dermatitis, with peanut allergy resolution. Sesame SPT, sesame-sIgE, Ses i 1-sIgE and MAT to sesame were all higher in sesame allergic participants compared to sesame sensitised but not allergic participants at all time points. Ses i 1-sIgE was the most useful predictive biomarker as our predictive model showed that an increased change of Ses i 1-sIgE from 1 to 3-years of age was predictive of new sesame allergy developing later in childhood. For egg, having higher egg white-sIgE was associated with an increased odds of having egg allergy persistence in later childhood. MATs to peanut, egg and sesame were significantly higher in the allergic children compared to those sensitised and not allergic for peanut, sesame, and egg, respectively. However, for sesame and egg, the proportion of CD63+ LAD2 cells was lower than expected and may not be of clinical significance. In the health economics part of the thesis, the main finding was that children with any atopic disease (i.e. food allergies, asthma, atopic dermatitis, allergic rhinitis) had higher total NHS costs compared to those without any atopic diseases. Children with atopy were more likely to utilise community and hospital-based services compared to children without atopy. Factors such as being younger or coming from a lower income household were associated with an increased level of total NHS healthcare costs.
Conclusions
This thesis provides information about the longitudinal trajectory of peanut, sesame and egg food allergies and the patterns of allergen-specific biomarkers that change across time. The prevalence rate of food allergies at 7-12-years of age for peanut, egg and sesame was 4.3% in this cohort of children from the general population, which represents a significant burden of food allergies. Peanut allergy remained stable at a prevalence rate of 2.3%, egg allergy decreased over time to a prevalence rate of 1.5% and sesame allergy increased over time to a prevalence of 1.5% by 7-12-years of age. Raised levels of Ses i 1-3 sIgE are predictive of new onset sesame allergy in later childhood, elevated levels of egg white-sIgE are predictive of egg allergy persistence and higher levels of peanut SPT or peanut-sIgE are associated with peanut allergy persistence. Children with atopy have a higher health economic burden with greater total NHS healthcare costs compared to children without atopy. With the rising rates of allergies globally, the burden of allergic disease will only continue to increase which means that any new information to help guide the diagnosis or management of children with food allergies is paramount.
| Date of Award | 1 Sept 2024 |
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| Original language | English |
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| Supervisor | Gideon Lack (Supervisor) & Alexandra Santos (Supervisor) |