Paediatrics (RCH) - Research Publications
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ItemPeanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol(BMC, 2013-09-12)BACKGROUND: The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients' threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals. METHODS/AIMS: This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children's Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre.A total of 375 participants, aged 1-18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed. CONCLUSION: The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population.
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ItemThe Natural History of IgE-Mediated Food Allergy: Can Skin Prick Tests and Serum-Specific IgE Predict the Resolution of Food Allergy?(MDPI, 2013-10)IgE-mediated food allergy is a transient condition for some children, however there are few indices to predict when and in whom food allergy will resolve. Skin prick test (SPT) and serum-specific IgE levels (sIgE) are usually monitored in the management of food allergy and are used to predict the development of tolerance or persistence of food allergy. The aim of this article is to review the published literature that investigated the predictive value of SPT and sIgE in development of tolerance in children with a previous diagnosis of peanut, egg and milk allergy. A systematic search identified twenty-six studies, of which most reported SPT or sIgE thresholds which predicted persistent or resolved allergy. However, results were inconsistent between studies. Previous research was hampered by several limitations including the absence of gold standard test to diagnose food allergy or tolerance, biased samples in retrospective audits and lack of systematic protocols for triggering re-challenges. There is a need for population-based, prospective studies that use the gold standard oral food challenge (OFC) to diagnose food allergy at baseline and follow-up to develop SPT and sIgE thresholds that predict the course of food allergy.
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ItemNo Preview AvailableHouse dust mite sensitization in toddlers predicts current wheeze at age 12 years(MOSBY-ELSEVIER, 2011-10)BACKGROUND: Identification of children at risk of developing asthma provides a window of opportunity for risk-reducing interventions. Allergen sensitization might identify high-risk children. OBJECTIVE: We sought to determine whether skin prick tests (SPTs) to individual allergens up to age 2 years predict wheeze at age 12 years. METHODS: In a birth cohort of 620 children oversampled for familial allergy, sensitization was assessed by using SPTs (monosensitized, polysensitized, or either) to 6 allergens at ages 6, 12, and 24 months. Wheeze and eczema were recorded 18 times during the first 2 years. Current wheeze was recorded at age 12 years. Adjusted associations were evaluated by multiple logistic regression. RESULTS: A positive SPT to house dust mite (HDM) at age 1 or 2 years predicted wheeze at age 12 years (adjusted odds ratio: 1 year, 3.31 [95% CI 1.59-6.91]; 2 years, 6.37 [95% CI, 3.48-11.66]). Among wheezy 1-year-olds, those who were HDM sensitized had a 75% (95% CI, 51% to 91%) probability of wheeze at age 12 years compared with a 36% (95% CI, 23% to 50%) probability among those not sensitized. Among eczematous 1-year-olds, those who were HDM sensitized had a 67% (95% CI, 45% to 84%) probability of wheeze at age 12 years compared with a 35% (95% CI, 25% to 45%) probability among those not sensitized. Among 1-year-old children with both eczema and wheeze, the probability of wheeze at age 12 years was 64% (95% CI, 35% to 87%) if HDM sensitized and 50% (95% CI, 26% to 74%) if not. CONCLUSION: HDM sensitization at age 1 or 2 years in wheezing and eczematous children at increased familial allergy risk predicts asthma and may inform management of these high-risk groups.
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ItemThe Impact of Family History of Allergy on Risk of Food Allergy: A Population-Based Study of Infants(MDPI AG, 2013-11)The apparent rapid increase in IgE-mediated food allergy and its implications are now widely recognized, but little is known about the relationship between family history (an indirect measure of genetic risk) and the risk of food allergy. In a population-based study of 5,276 one year old infants (HealthNuts), the prevalence of oral food challenge-confirmed food allergy was measured. Associations between family history of allergic disease and food allergy in infants were examined using multiple logistic regression. Food allergy was diagnosed in 534 infants. Compared to those with no family history of allergic disease, children meeting the current definition of "high risk" for allergic disease (one immediate family member with a history of any allergic disease) showed only a modest increase (OR 1.4, 95% CI 1.1-1.7) in food allergy, while having two or more allergic family members was more strongly predictive of food allergy in the child (OR 1.8, 95% CI 1.5-2.3). There were also differences in the associations between family history and egg and peanut allergy in the child. Re-defining "high risk" as two or more allergic family members may be more useful for identification of groups with a significantly increased risk of food allergy both clinically and within research studies.
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ItemPopulation Response To Change In Infant Feeding Guidelines For Allergy Prevention(MOSBY-ELSEVIER, 2014-02)
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ItemA phase I study of daily treatment with a ceramide-dominant triple lipid mixture commencing in neonates(BIOMED CENTRAL LTD, 2012-04-04)BACKGROUND: Defects in skin barrier function are associated with an increase risk of eczema and atopic sensitisation. Ceramide-dominant triple lipid mixture may improve and maintain the infant skin barrier function, and if shown to be safe and feasible, may therefore offer an effective approach to reduce the incidence of eczema and subsequent atopic sensitisation. We sort to assess the safety and compliance with daily application of a ceramide-dominant triple lipid formula (EpiCeram™) commencing in the neonatal period for the prevention of eczema. METHODS: Ten infants (0-4 weeks of age) with a family history of allergic disease were recruited into an open-label, phase one trial of daily application of EpiCeram™ for six weeks. The primary outcomes were rate of compliance and adverse events. Data on development of eczema, and physiological properties of the skin (transepidermal water loss, hydration, and surface pH) were also measured. RESULTS: Eighty percent (8/10) of mothers applied the study cream on 80% or more of days during the six week intervention period. Though a number of adverse events unrelated to study product were reported, there were no adverse skin reactions to the study cream. CONCLUSIONS: These preliminary results support the safety and parental compliance with daily applications of a ceramide-dominant formula for the prevention of eczema, providing the necessary ground work for a randomised clinical trial to evaluate EpiCeram™ for the prevention of eczema. TRIAL REGISTRATION: The study was listed at the Australian/New Zealand Clinical Trial Registry (ANZCTR): reg. no. ACTRN12609000727246.
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ItemSNP selection for genes of iron metabolism in a study of genetic modifiers of hemochromatosis(BMC, 2008-03-20)BACKGROUND: We report our experience of selecting tag SNPs in 35 genes involved in iron metabolism in a cohort study seeking to discover genetic modifiers of hereditary hemochromatosis. METHODS: We combined our own and publicly available resequencing data with HapMap to maximise our coverage to select 384 SNPs in candidate genes suitable for typing on the Illumina platform. RESULTS: Validation/design scores above 0.6 were not strongly correlated with SNP performance as estimated by Gentrain score. We contrasted results from two tag SNP selection algorithms, LDselect and Tagger. Varying r2 from 0.5 to 1.0 produced a near linear correlation with the number of tag SNPs required. We examined the pattern of linkage disequilibrium of three levels of resequencing coverage for the transferrin gene and found HapMap phase 1 tag SNPs capture 45% of the > or = 3% MAF SNPs found in SeattleSNPs where there is nearly complete resequencing. Resequencing can reveal adjacent SNPs (within 60 bp) which may affect assay performance. We report the number of SNPs present within the region of six of our larger candidate genes, for different versions of stock genotyping assays. CONCLUSION: A candidate gene approach should seek to maximise coverage, and this can be improved by adding to HapMap data any available sequencing data. Tag SNP software must be fast and flexible to data changes, since tag SNP selection involves iteration as investigators seek to satisfy the competing demands of coverage within and between populations, and typability on the technology platform chosen.
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ItemThe prevalence and socio-demographic risk factors of clinical eczema in infancy: a population-based observational study(WILEY, 2013-06)BACKGROUND: Socio-demographic predictors for the development of clinically observed, infantile eczema have not been formally examined in a large population-based study. Few studies of eczema risk factors have included current, objective eczema outcomes as well as parent-reported history. OBJECTIVES: We aimed to measure the population prevalence of infantile eczema using novel sampling methodology, and identify socio-demographic risk factors for eczema in the first year of life. METHODS: A population-based cross-sectional study of infantile allergy (the HealthNuts study, n = 4972, response rate 74.1%) was conducted from 2008-2011 in Melbourne, Australia. Infants were examined for current eczema at age 12 months (mean 12.7, SD 0.7). Parents provided information about the infants' history of eczema and demographic factors. Factors associated with eczema were modelled using multinomial logistic regression. RESULTS: The population prevalence of observed eczema at 12 months was 20.3% (95% CI 19.0, 21.5), while cumulative prevalence for parent-reported eczema was 28.0% (95% CI 26.7, 29.4). The strongest predictors of eczema were maternal eczema and asthma (multinomial (M)-OR 1.7, P < 0.001, and M-OR 1.4, P = 0.007), male sex (M-OR 1.4, P < 0.001), and East Asian ethnicity (M-OR 1.6, P < 0.001) with over 80% of infants with all risk factors exhibiting eczema. East Asian parents, particularly recent migrants, reported fewer allergies than other parents. CONCLUSIONS AND CLINICAL RELEVANCE: Approximately, one in three infants developed eczema by 12 months of age. East Asian infants are at increased risk of eczema despite their parents having lower rates of allergy than non-Asian parents. Gene-environment interactions may explain the differential effect seen in this minority group.
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