Paediatrics (RCH) - Research Publications

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    Variability in Skin Prick Test Results Performed by Multiple Operators Depends on the Device Used
    Werther, RL ; Choo, S ; Lee, KJ ; Poole, D ; Allen, KJ ; Tang, MLK (BIOMED CENTRAL LTD, 2012)
    BACKGROUND: : The variability of skin prick test results when carried out by multiple users has not previously been assessed across different devices or between different sites on the body. Such multiuser variability has important implications for clinical practice. OBJECTIVES: : We assessed the variability of measurements from 4 commonly used single-headed skin test devices when used by multiple operators and examined whether the variability in performance was different on the back compared with the forearm. METHODS: : Eight adult volunteer "operators" were trained in the use of 4 devices: Greer Pick, Quintip, Stallergenes Lancet, and Feather Lancet. Each operator performed a histamine skin prick test with all devices on the backs and forearms of 5 volunteer "receivers." Variability in results was assessed using a multilevel (random effects) regression model. RESULTS: : After controlling for variation between users and receivers, the residual variability or "measurement error" was least for the Stallergenes Lancet, closely followed by the Quintip. The Greer Pick had the greatest variability. There was greater variability in measurements on the arm compared with the back. CONCLUSIONS: : The devices using the "puncture" method (Stallergenes Lancet, Quintip) provide less variability in results than those using a "prick" method when carried out by multiple users (Greer Pick and Feather Lancet). Testing on the back also gives less variable results compared with the arm.
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    House dust mite sensitization in toddlers predicts current wheeze at age 12 years
    Lodge, CJ ; Lowe, AJ ; Gurrin, LC ; Hill, DJ ; Hosking, CS ; Khalafzai, RU ; Hopper, JL ; Matheson, MC ; Abramson, MJ ; Allen, KJ ; Dharmage, SC (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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    A phase I study of daily treatment with a ceramide-dominant triple lipid mixture commencing in neonates
    Lowe, AJ ; Tang, MLK ; Dharmage, SC ; Varigos, G ; Forster, D ; Gurrin, LC ; Robertson, CF ; Abramson, MJ ; Allen, KJ ; Su, J (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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    SNP selection for genes of iron metabolism in a study of genetic modifiers of hemochromatosis
    Constantine, CC ; Gurrin, LC ; McLaren, CE ; Bahlo, M ; Anderson, GJ ; Vulpe, CD ; Forrest, SM ; Allen, KJ ; Gertig, DM (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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    Filaggrin loss-of-function mutations do not predict food allergy over and above the risk of food sensitization among infants
    Tan, H-TT ; Ellis, JA ; Koplin, JJ ; Matheson, MC ; Gurrin, LC ; Lowe, AJ ; Martin, PE ; Dang, TD ; Wake, M ; Tang, MLK ; Ponsonby, A-L ; Dharmage, SC ; Allen, KJ (MOSBY-ELSEVIER, 2012-11)