Papers by Jennifer Koplin
Journal of Allergy and Clinical Immunology, 2012
Allergy, 2014
Asian infants appear to be over-represented among patients with clinical food allergy in Australi... more Asian infants appear to be over-represented among patients with clinical food allergy in Australia, but this has not been formally examined at the population level. Any difference in prevalence according to parental country of birth may be secondary to modifiable lifestyle factors. We aimed to quantify (i) differences in the prevalence of peanut allergy by parental country of birth and (ii) contribution of measured environmental exposures to these differences. The population-based HealthNuts study in Melbourne, Australia, screened 5276 infants (74% participation) with skin prick tests and sensitized infants underwent food challenge. Of these, 535 had a parent born in East Asia and 574 in UK/Europe. Associations between parents' country of birth and offspring peanut allergy were examined using multiple logistic regression. Compared to infants with two Australian-born parents, peanut allergy was more common among infants with parent/s born in East Asia (OR 3.4, 95% CI 2.2-5.1) but...
International journal of epidemiology, Jan 21, 2015
HealthNuts is a single-centre, multi-wave, population-based longitudinal study designed to assess... more HealthNuts is a single-centre, multi-wave, population-based longitudinal study designed to assess prevalence, determinants, natural history and burden of allergy (particularly food allergy) in the early years of life. It is novel in the use of serial food challenge measures within its population frame to confirm food allergy. The cohort comprises 5276 children initially recruited at age 12 months from council-run immunization sessions across Melbourne, Australia. As well as parent-completed questionnaires and researcher-observed eczema status, all infants underwent skin-prick testing to egg, peanut, sesame and either cow's milk or shellfish, and those with detectable wheals underwent food challenges to determine clinical allergy. In wave 2, conducted at age 4 years, validated questionnaires collected data on asthma, allergic rhinitis (hay fever), eczema and food allergies. Food challenges were repeated in children previously identified as food allergic to determine resolution. I...
Journal of Allergy and Clinical Immunology, 2015
There are no prospectively collected data available on the natural history of peanut allergy in e... more There are no prospectively collected data available on the natural history of peanut allergy in early childhood. Previous studies of predictors of tolerance development have been biased by failure to challenge high-risk children when IgE antibody levels are high, therefore potentially introducing bias to persistent allergy. We sought to describe the natural history of peanut allergy between 1 and 4 years of age and develop thresholds for skin prick test (SPT) results and specific IgE (sIgE) levels measured at age 1 and 4 years that have 95% positive predictive value (PPV) or negative predictive value for the persistence or resolution of peanut allergy. One-year-old infants with challenge-confirmed peanut allergy (n = 156) from the population-based, longitudinal HealthNuts Study (n = 5276) were followed up at 4 years of age with repeat oral food challenges, SPTs, and sIgE measurements (n = 103). Challenges were undertaken in all peanut-sensitized children at 1 and 4 years of age, irrespective of risk profile. Peanut allergy resolved in 22% (95% CI, 14% to 31%) of children by age 4 years. Decreasing wheal size predicted tolerance, and increasing wheal size was associated with persistence. Thresholds for SPT responses and sIgE levels at age 1 year with a 95% PPV for persistent peanut allergy are an SPT-induced response of 13 mm or greater and an sIgE level of 5.0 kU/L or greater. Thresholds for SPT and sIgE results at age 4 years with a 95% PPV for persistent peanut allergy are an SPT response of 8 mm or greater and an sIgE level of 2.1 kU/L or greater. Ara h 2, tree nut, and house dust mite sensitization; coexisting food allergies; eczema; and asthma were not predictive of persistent peanut allergy. These thresholds are the first to be generated from a unique data set in which all participants underwent oral food challenges at both diagnosis and follow-up, irrespective of SPT and sIgE results.
International Journal of Environmental Research and Public Health, 2013
The apparent rapid increase in IgE-mediated food allergy and its implications are now widely reco... more 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
The Journal of Allergy and Clinical Immunology: In Practice, 2013
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.
Journal of Allergy and Clinical Immunology, 2015
for the HealthNuts study investigators Parkville, Melbourne, and Perth, Australia, and Manchester... more for the HealthNuts study investigators Parkville, Melbourne, and Perth, Australia, and Manchester, United Kingdom Background: The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. Objective: We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Methods: Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA. Results: Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes.
The Journal of Steroid Biochemistry and Molecular Biology, 2014
We aimed to investigate the relationship between genetic and environmental exposure and vitamin D... more We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy.
Pediatric Allergy and Immunology, 2008
Is caesarean delivery associated with sensitization to food allergens and IgE-mediated food aller... more Is caesarean delivery associated with sensitization to food allergens and IgE-mediated food allergy: A systematic review Food allergies have a significant impact on the quality of life of both affected individuals and their families (1, 2). The prevalence of food allergy varies both internationally and regionally, however a recent review estimated that approximately 6% of children under the age of 3 yr are affected (3). The number of hospital admissions for food allergy in the UK is estimated to have risen by 500% since 1990 (4) and a similar trend appears to be occurring in Australia (5). The reason for this apparent increase in food allergy is unclear although the increase in incidence is occurring more rapidly than could be explained by genetic factors Koplin J, Allen K, Gurrin L, Osborne N, Tang MLK, Dharmage S. Is caesarean delivery associated with sensitization to food allergens and IgE-mediated food allergy: A systematic review.
Journal of Allergy and Clinical Immunology, 2014
It is unknown whether population infant feeding practices have changed since recently revised Aus... more It is unknown whether population infant feeding practices have changed since recently revised Australian allergy guidelines removed recommendations to delay allergenic solids. We sought to determine whether updated 2008 guidelines were associated with changes in feeding practice and to determine whether sociodemographic factors influenced this response. In a population-based, cross-sectional study (HealthNuts) of 5276 infants recruited between 2007 and 2011 in Melbourne, Australia, parents reported on infant feeding practices. Multinomial logistic regression was used to investigate the associations between recruitment year and feeding practices and whether these associations were modified by sociodemographic factors. Compared with participants recruited in 2007-2009, those recruited in 2009-2011 were more likely to introduce solids at age 4 months (adjusted multinomial odds ratio [aMOR], 1.21; 95% CI, 1.02-1.45; P = .032) and less likely to introduce solids at age 6 months (aMOR, 0.80; 95% CI, 0.69-0.92; P = .002), egg after 6 months (aMOR, 0.82; 95% CI, 0.71-0.94; P = .004), and peanut after 12 months (aMOR, 0.70; 95% CI, 0.49-0.98; P = .037). Although parents recruited in 2009-2011 were less likely to formula feed (aMOR, 0.84; 95% CI, 0.72-0.98; P = .023), formula-fed infants were more likely to be given a partially hydrolyzed formula (aMOR, 1.37; 95% CI, 1.12-1.70; P = .003). These changes were significantly stronger among families with a higher socioeconomic status and those without a family history of allergies. Updated national allergy guidelines are associated with reduced delay in introduction of solids, egg, and peanut and an increase in partially hydrolyzed formula use among formula-fed infants. Higher socioeconomic status and absence of family history of allergies were associated with better uptake of feeding guidelines.
Journal of Allergy and Clinical Immunology, 2010
Journal of Allergy and Clinical Immunology, 2013
Journal of Allergy and Clinical Immunology, 2008
A recent cohort study suggested that intake of soy milk or soy formula was associated with peanut... more A recent cohort study suggested that intake of soy milk or soy formula was associated with peanut allergy. If this finding is confirmed, it suggests an avenue for modification of diet as a peanut allergy prevention strategy. To investigate the relationship between soy consumption and peanut sensitization in a prospective cohort study of children. A total of 620 babies with a family history of allergic disease were recruited. Dietary information was obtained from telephone interviews every 4 weeks from birth until 15 months and then again at 18 months and 2 years. Skin prick tests to peanut, milk, and egg were performed at 6, 12, and 24 months. A wheal size > or = 3 mm was considered positive for sensitization. Children whose parents elected to introduce soy formula or soy milk into their children's diet were more likely to be sensitized to peanuts at 2 years (odds ratio, 2.02; 95% CI, 1.04-3.92; P = .039). However, this relationship was explained by feeding of soy to children who had siblings with milk allergy or were themselves sensitized to milk. After adjusting for these factors, there was no evidence of an association between soy consumption and peanut sensitization (odds ratio, 1.34; 95% CI, 0.64-2.79; P = .434). The association between soy consumption and peanut sensitization is not causal but merely a result of preferential use of soy milk in infants with a personal or family history of cow's milk allergy. Future studies should take the confounding effects related to dietary modifications by parents into account when investigating the association between diet and childhood allergic diseases.
Journal of Allergy and Clinical Immunology, 2008
Description A recent widely quoted study found that intake of soy in the first two years of life ... more Description A recent widely quoted study found that intake of soy in the first two years of life was associated with peanut allergy (Lack et al, NEJM 2003) suggesting that prior sensitisation to soy leads to peanut allergy. We investigated the relationship between soy consumption and peanut sensitisation in a prospective longitudinal cohort study.
Journal of Allergy and Clinical Immunology, 2011
Background: Several indicators suggest that food allergy in infants is common and possibly increa... more Background: Several indicators suggest that food allergy in infants is common and possibly increasing. Few studies have used oral food challenge to measure this phenomenon at the population level. Objective: To measure the prevalence of common IgE-mediated childhood food allergies in a population-based sample of 12-month-old infants by using predetermined food challenge criteria to measure outcomes. Methods: A sampling frame was used to select recruitment areas to attain a representative population base. Recruitment occurred at childhood immunization sessions in Melbourne, Australia. Infants underwent skin prick testing, and those with any sensitization (wheal size > _1 mm) to 1 or more foods (raw egg, peanut, sesame, shellfish, or cow's milk) were invited to attend an allergy research clinic. Those who registered a wheal size > _1 mm to raw egg, peanut, or sesame underwent oral food challenge. Results: Amongst 2848 infants (73% participation rate), the prevalence of any sensitization to peanut was 8.9% (95% CI, 7.9-10.0); raw egg white, 16.5% (95% CI, 15.1-17.9); sesame, 2.5% (95% CI, 2.0-3.1); cow's milk, 5.6% (95% CI, 3.2-8.0); and shellfish, 0.9% (95% CI, 0.6-1.5). The prevalence of challenge-proven peanut allergy was 3.0% (95% CI, 2.4-3.8); raw egg allergy, 8.9% (95% CI, 7.8-10.0); and sesame allergy, 0.8% (95% CI, 0.5-1.1). Oral food challenges to cow's milk and shellfish were not performed. Of those with raw egg allergy, 80.3% could tolerate baked egg. Conclusion: More than 10% of 1-year-old infants had challengeproven IgE-mediated food allergy to one of the common allergenic foods of infancy. The high prevalence of allergic disease in Australia requires further investigation and may be related to modifiable environmental factors. (J Allergy Clin Immunol 2011;127:668-76.)
Clinical Biochemistry, 2014
Food allergy has a dramatic impact on a child's (and their family's) quality of life and places a... more Food allergy has a dramatic impact on a child's (and their family's) quality of life and places a major financial burden on the community. It has been hypothesized that the increase in food allergy may relate to the concordant rise in prevalence of vitamin D insufficiency. More recently a second hypothesis has implicated vitamin A sufficiency in the development of immune tolerance. Together, these hypotheses have prompted investigation into the circulating levels of vitamins A and D in relation to food allergy prevalence. This review aims to examine the relationship between vitamins A and D and food allergy. The first part of this review presents the available epidemiological data which proposes a dramatic increase of food allergy and related anaphylaxis during the last two decades. There is some indirect evidence that variation in food allergy prevalence within countries might be linked with ambient ultra violet radiation exposure and thus potentially with vitamin D levels. Only a few studies to date have directly examined the relationship between measured serum vitamin D levels and either food sensitization or allergy. The significance of vitamin A in food allergy prevalence is only provided through a hypothetical association due to its role in the immune system. The second part of this review discusses the relevant aspects of the analytical methods to assess vitamin A and D levels in children. The primary methods utilized relate to measuring the main circulating forms of vitamins A and D in blood i.e. retinol and 25-hydroxy-vitamin-D 3 respectively. Chromatographic separation coupled with mass spectrometric detection is considered the gold standard method for both vitamins. These analytical methods should be fully validated for the use in pediatric populations to ensure they are fit for their clinical purpose.
FOOD ALLERGY, Nov 1, 2011
Background: Research into risk factors for food allergy has focused on the role of timing of firs... more Background: Research into risk factors for food allergy has focused on the role of timing of first exposure to allergenic foods on the subsequent development of food allergy. This research requires the collection of accurate questionnairebased data on allergen exposure, which in turn requires accurate parental knowledge of the dietary allergen content of foods.
Background: There is a paucity of data examining the natural history of and risk factors for egg ... more Background: There is a paucity of data examining the natural history of and risk factors for egg allergy persistence, the most common IgE-mediated food allergy in infants. Objective: We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort. Methods: The HealthNuts study is a prospective, populationbased cohort study of 5276 infants who underwent skin prick tests to 4 allergens, including egg. Infants with a detectable wheal were offered hospital-based oral food challenges (OFCs) to egg, irrespective of skin prick test wheal sizes. Infants with challengeconfirmed raw egg allergy were offered baked egg OFCs at age 1 year and follow-up at age 2 years, with repeat OFCs to raw egg. Results: One hundred forty infants with challenge-confirmed egg allergy at age 1 year participated in the follow-up. Egg allergy resolved in 66 (47%) infants (95% CI, 37% to 56%) by 2 years of age; however, resolution was lower in children with baked egg allergy at age 1 year compared with baked egg tolerance (13% and 56%, respectively; adjusted odds ratio, 5.27; 95% CI, 1.36-20.50; P 5.02). In the subgroup of infants who were tolerant to baked egg at age 1 year, frequent ingestion of baked egg (> _5 times per month) compared with infrequent ingestion (0-4 times per month) increased the likelihood of tolerance (adjusted odds ratio, 3.52; 95% CI, 1.38-8.98; P 5 .009). Mutation in the filaggrin gene was not associated with the resolution of either egg allergy or egg sensitization at age 2 years. Conclusion: Phenotyping of egg allergy (baked egg tolerant vs allergic) should be considered in the management of this allergy because it has prognostic implications and eases dietary restrictions. Randomized controlled trials for egg oral immunotherapy should consider stratifying at baseline by the baked egg subphenotype to account for the differential rate of tolerance development. (J Allergy Clin Immunol 2014;133:485-91.)
Journal of Allergy and Clinical Immunology, 2013
Background: Epidemiological evidence has shown that pediatric food allergy is more prevalent in r... more Background: Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. Objective: To investigate the role of vitamin D status in infantile food allergy. Methods: A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cow's milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. Results: Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (< _50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P 5 .006) and/or egg (aOR, 3.79; 95% CI, 1.19-12.08; P 5 .025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (> _2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). Conclusions: These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life. (J Allergy Clin Immunol 2013;131:1109-16.)
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Papers by Jennifer Koplin