ORCID Profile
0000-0002-1921-4493
Current Organisations
University of Manchester
,
Royal Children’s Hospital
,
Murdoch Childrens Research Institute
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Publisher: Elsevier BV
Date: 2013
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/JPC.13109
Abstract: To determine whether infant-feeding practices, including duration of exclusive breastfeeding and use of partially hydrolysed formula, modify the risk of developing infant food allergy. In an observational population-based study, 1 year olds were recruited from community immunisation clinics in Melbourne, Australia. Parent-reported data on infant-feeding practices and potential confounders were collected prior to infant skin prick testing for four food allergens. Sensitised infants attended hospital-based oral food challenges to establish food allergy status. Multiple logistic regression was used to investigate associations between breastfeeding and formula-feeding and infant food allergy adjusting for possible confounding variables. A total of 5276 (74% response) infants participated. Of the 4537 for whom food allergy status was determined, 515 (11.3%) were food allergic (challenge-proven in the context of skin prick testing positive (≥2 mm)). After adjusting for confounding variables, there was no association between duration of exclusive breastfeeding and food allergy. Use of partially hydrolysed formula did not reduce the risk of food allergy compared with cow's milk formula in the general population (adjusted odds ratios 1.03 (confidence interval 0.67-1.50)). Duration of exclusive breastfeeding and use of partially hydrolysed formula were not associated with food allergy at 1 year of age in this large population-based study. These findings have implications for population-based infant-feeding guidelines and do not support the use of partially hydrolysed formula for food allergy prevention.
Publisher: Wiley
Date: 26-02-2014
DOI: 10.1111/JPC.12498
Abstract: The prevalence of Immunoglobulin E (IgE)-mediated food allergy in the developed world is increasing, overwhelming tertiary allergy services. Alternative models of care are required. General paediatricians could provide this care but may require further training to do so. We aimed to determine Australian general paediatricians': (i) knowledge and management of IgE-mediated food allergy (ii) access to and use of diagnostic services and (iii) interest in further training. Members of the Australian Paediatric Research Network completed an online survey in 2011/12. A case study elicited paediatrician's knowledge of diagnostic history taking, testing and key management principles. Study-designed questions assessed paediatricians' current practice, access to allergy services and interest in further training. One hundred sixty-eight (43%) of 390 paediatricians responded 93 paediatricians reported managing food allergy. Diagnostic and management practices varied widely. Paediatricians had high levels of agreement (>90%) for only three of 13 questions pertaining to diagnosis and management. Only 56 (61%) correctly identified that a diagnosis of IgE-mediated food allergy requires a history consistent with a clinical reaction and a positive specific serum IgE antibody or skin prick test result. Reported waiting times for tertiary allergy services ranged from 5.4 (private) to 10.6 months (public). Most (91%) paediatricians expressed interest in further training. General paediatricians would benefit from further training if they are to practice allergy care as their diagnosis and management is often inconsistent with international guidelines. Training could be delivered online to maximise reach and uptake. If effective, such a model could relieve some of the burden experienced by Australian tertiary allergy services.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.JACI.2010.05.006
Abstract: Partially hydrolyzed whey formula (pHWF) has been recommended for infants with a family history of allergic disease at the cessation of exclusive breast-feeding to promote oral tolerance and prevent allergic diseases. To determine whether feeding infants pHWF reduces their risk of allergic disease. A single-blind (participant) randomized controlled trial was conducted to compare allergic outcomes between infants fed a conventional cow's milk formula, a pHWF, or a soy formula. Before birth, 620 infants with a family history of allergic disease were recruited and randomized to receive the allocated formula at cessation of breast-feeding. Skin prick tests to 6 common allergens (milk, egg, peanut, dust mite, rye grass, and cat dander) were performed at 6, 12, and 24 months. The primary outcome was development of allergic manifestations (eczema and food reactions) measured 18 times in the first 2 years of life. Follow-up was complete for 93% (575/620) at 2 years and 80% (495/620) at 6 or 7 years of age. There was no evidence that infants allocated to the pHWF (odds ratio, 1.21 95% CI, 0.81-1.80) or the soy formula (odds ratio, 1.26 95% CI, 0.84-1.88) were at a lower risk of allergic manifestations in infancy compared with conventional formula. There was also no evidence of reduced risk of skin prick test reactivity or childhood allergic disease. Despite current dietary guidelines, we found no evidence to support recommending the use of pHWF at weaning for the prevention of allergic disease in high-risk infants.
Publisher: MDPI AG
Date: 27-07-2015
DOI: 10.3390/NU7085271
Publisher: Wiley
Date: 04-05-2017
DOI: 10.1111/PAI.12714
Abstract: Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood. A high-risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow-ups. Very early-onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7-6.1]), as was very early-onset remitting eczema (onset <6 months but not present from 2-5 years, OR = 2.7, 95% CI = 1.0-7.2) and early-onset persistent eczema (onset from 6-24 months, OR = 2.3, 95% CI = 1.2-4.7). Late-onset eczema (commenced from 2-5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1-8.2) but not at age 6 years. Only very early-onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4-4.1). Eczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high-risk children. If these associations are causal, prevention of early-life eczema might reduce the risk of respiratory allergy.
Publisher: Wiley
Date: 13-11-2018
DOI: 10.1111/CEA.13290
Abstract: Markers of microbial exposure are thought to be associated with risk of allergic sensitization however, the associations are inconsistent and may be related to gene-environment interactions. To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship. We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi-level mixed-effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random-effects meta-analysis. CD14 SNPs were not in idually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta-analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455-SNP (P = 0.001) but not with the rs2569190-SNP (P = 0.60). The pooled meta-analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455-C-allele than the T-allele (OR = 0.83 vs 1.05, respectively). Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible in iduals.
Publisher: Wiley
Date: 17-09-2018
DOI: 10.1111/PAI.12959
Abstract: Peanut allergy is classically managed by food avoidance. Immunotherapy programs are available at some academic centers for selected patients reacting to small amounts of peanut during food challenge. We aimed to determine and compare reaction thresholds and prevalence of anaphylaxis during peanut oral challenges at multiple specialist allergy centers. A retrospective, international survey of anonymized case records from seven specialist pediatric allergy centers from the UK and Ireland, as well as the Australian HealthNuts study. Demographic information, allergy test results, reaction severity and threshold during open oral peanut challenges were collated and analyzed. Of the 1634 children aged 1-18 years old included, 525 (32%) failed their peanut challenge. Twenty-eight percent reacted to 25 mg, while 38% only reacted after consuming 1 g or more of whole peanut. Anaphylaxis (55 [11%]) was 3 times more common in teenagers than younger children and the likelihood increased at all ages as children consuming more peanut at the challenge. Children who developed anaphylaxis to 25-200 mg of whole peanut were significantly older. Previous history of reaction did not predict reaction threshold or severity. More than a third of the children in this large international cohort tolerated the equivalent of one peanut in an oral challenge. Anaphylaxis, particularly to small amounts of peanut, was more common in older children. Tailored immunotherapy programs might be considered not only for children with low, but also higher reaction thresholds. Whether these programs could prevent heightened sensitivity and anaphylaxis to peanut with age also deserves further study.
Publisher: Wiley
Date: 25-09-2015
DOI: 10.1111/ALL.12687
Publisher: Wiley
Date: 12-06-2017
DOI: 10.1111/JPC.13594
Abstract: Early feeding plays an important role in programming the immune system, particularly the risk of food allergy. There are many infant feeding guides published for consumers available in Australia, with most based on the National Health and Medical Research Council (NHMRC) 2012 Infant Feeding Guidelines for Health Workers and the Australasian Society of Clinical Immunology and Allergy (ASCIA) Infant Feeding Advice for allergy prevention. We sought to compare allergy-specific content of infant feeding educational material written for parents with these two documents. Australian websites of children's hospitals, early child health organisations and consumer groups providing information about diet during pregnancy, breastfeeding and early infancy were compared with NHMRC and ASCIA guidelines. Twenty-five sets of infant feeding information were identified. Food allergy was discussed in 18 resources. Recommended length of exclusive breastfeeding and timing of commencing solid foods was consistently around 6 months, with some variation in wording. Advice regarding to include and not delay introduction of common allergens into babies' diets was generally consistent with NHMRC and ASCIA recommendations, however the audit identified some resources that still recommended delayed introduction of common allergens. As consumers have access to a plethora of health information it is imperative that information about infant feeding from health-care authorities is simple, evidence-based and consistent to avoid confusion. Use of consensus wording related to infant feeding guidelines to prevent allergies will provide clear messages related to the timing of introduction to solid foods and inclusion of allergens in the early diet.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.CLINBIOCHEM.2014.01.033
Abstract: 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-D3 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2009
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JAIP.2017.12.011
Abstract: Despite the rising rates of anaphylaxis in older children and adolescents, risk factors for food allergy among this age group are understudied. The objective of this study was to investigate the risk factors for current adolescent food allergy using a population-based s le. The SchoolNuts study was a questionnaire survey among 10- to 14-year-old adolescents and their parents, followed by clinic evaluation including oral food challenge when food allergy was suspected from questionnaire response. We investigated the association between food allergy and demographic and environmental factors among a total of 4,991 adolescents using multiple logistic regression. Males and those with early-onset eczema had a higher risk of current food allergy in adolescence (adjusted odds ratio [aOR], 1.55 95% confidence interval [CI], 1.12-2.15 and aOR, 14.08 95% CI, 10.25-19.33). Those with Asian parents had increased risk compared with those with Caucasian parents (aOR, 2.82 95% CI, 1.91-4.16), whereas being born in Asia compared with being born in Australia had decreased risk (aOR, 0.16 95% CI, 0.04-0.67). Family history risk was higher for those with multiple members versus only 1 member (aOR, 4.62 95% CI, 2.75-7.74 and aOR, 2.32 95% CI, 1.36-3.97, respectively). Dog exposure during the first 5 years of life was associated with a decreased risk (aOR, 0.58 95% CI, 0.38-0.91). Early-onset eczema, Asian background, and family history of allergic disease were associated with an increased risk of food allergy, whereas dog exposure in early life reduced the risk in 10- to14-year-old adolescents. Factors predicting food allergy risk in an adolescent population-based cohort appear remarkably similar to those predicting early-onset food allergy in infancy.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.JAIP.2018.06.025
Abstract: Adolescence is well recognized as a period of increased risk for severe and fatal food-induced anaphylaxis. Current Australian adrenaline autoinjector (AAI) prescription guidelines therefore suggest that consideration be given to AAI prescription in all adolescents with a food allergy. To date, however, few studies have assessed the AAI carriage behavior of adolescents prescribed AAI devices. To determine the carriage behavior of prescribed AAI devices in a population-based s le of young Australian adolescents. Students aged 10 to 14 years (and their parents) from randomly selected schools in metropolitan Melbourne completed self-administered questionnaires regarding the history and management of food allergy, including prescription and carriage of AAI device in different domains of school and social life. A total of 9816 students completed the questionnaire (46% response): 620 students were assessed to have likely IgE-mediated food allergy and 234 (38%) of these had been prescribed an AAI. Most students (93% 95% CI, 89%-96%) who were prescribed AAIs reported that they provided their AAI and anaphylaxis action plan to their school. Adherence to AAI carriage in other domains of social life was poor, with 49% (95% CI, 42%-56%) never carrying their AAI in 1 or more locations. Carriage of the AAI device was particularly poor when students were independent of parental supervision: 32% (95% CI, 25%-39%) never carried it when they were by themselves, 28% (95% CI, 22%-36%) never carried it while out with friends, and 36% (95% CI, 30%-43%) never carried their AAI to sporting activities. Carriage of AAI devices is suboptimal in young adolescents prescribed AAIs, particularly when young adolescents are independent of parental supervision.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/176484
Abstract: Background . The literature is contradictory concerning pet exposure and the risk of development of asthma and other allergic diseases. Using longitudinal studies, we aimed to systematically review the impact of pet ownership in the critical perinatal period as a risk factor for allergies in childhood. Methods . Medline database was searched for urban cohort studies with perinatal exposure to cats and/or dogs and subsequent asthma or allergic disease. Results . Nine articles, comprising 6498 participants, met inclusion criteria. Six found a reduction in allergic disease associated with perinatal exposure to dogs or, cats or dogs. One study found no association. Two found increased risk only in high-risk groups. Conclusion . Longitudinal studies in urban populations suggest that perinatal pets, especially dogs, may reduce the development of allergic disease in those without a family history of allergy. Other unmeasured factors such as pet-keeping choices in allergic families may be confounding the association seen in these high-risk families, and further study is required.
Publisher: Elsevier BV
Date: 10-2015
Publisher: Wiley
Date: 11-01-2017
DOI: 10.1111/CEA.12863
Abstract: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. To identify genetic variants associated with challenge-proven peanut allergy. We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. We identified 21 independent associations at P ≤ 5 × 10 Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JIM.2015.04.016
Abstract: Data is now emerging that many human diseases not previously considered immune diseases have an immunological basis. As such human immunology is in need of more standardized systems-wide methods for monitoring immune regulation. Despite significant advances in basic immunology research, thousands of patients visiting health practitioners daily still have no reliable immunological metrics by which to assess the status of their immune health beyond the standard blood count. Further investigations are costly, time consuming and often don't offer significant insights into the mechanics of immune deviation or regulation. The immune system meets many criteria of complex biological networks and therefore systems-wide approaches are highly suitable to determining the emergent properties of immune responses. Standardization of immune monitoring, the development of new technology and integrated informatics approaches are needed in order to identify useful hematological and serological markers that are informative for immune health. This brief review outlines some of the more promising developments in systems immunology.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JACI.2014.12.1933
Abstract: 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. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. 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 s les by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays.
Publisher: Informa UK Limited
Date: 24-04-2014
DOI: 10.4161/EPI.28945
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1053/J.GASTRO.2008.08.056
Abstract: There are few longitudinal studies of serum ferritin (SF) and transferrin saturation (TS) levels in in iduals homozygous for the C282Y mutation. We characterized the development of elevated iron measures in C282Y homozygotes followed for 12 years. From 31,192 people aged 40-69 years at baseline, we identified 203 C282Y homozygotes (95 males), of whom 116 had SF and fasting TS levels measured at baseline (mean age, 55 years) and 86 were untreated and had iron measures at follow-up (mean, 12 years later). The probabilities of SF at follow-up exceeding clinical thresholds were predicted from baseline SF and TS under a multivariate normal model. For C282Y homozygotes, at baseline, 84% of males and 65% of females had elevated SF and 37% of males and 3% of females had SF >1000 microg/L. For males with SF 300-1000 microg/L at baseline, the predicted probability of progressing to SF >1000 microg/L at follow-up was between 13% and 35% and, for females, between 16% and 22%. For C282Y homozygotes with normal baseline SF, 1000 microg/L if left untreated. The majority of C282Y homozygotes who are likely to develop SF levels sufficient to place them at risk of iron overload-related disease will have done so by mean age 55 years. TS >95% at mean age 55 years in males increases the likelihood that SF levels will be elevated at mean age 65 years, but this effect is absent in females, most likely because of physiologic blood loss associated with menstruation.
Publisher: Wiley
Date: 04-12-2011
DOI: 10.1111/J.1399-3038.2011.01237.X
Abstract: Immunoglobulin E-mediated (IgE) food allergy affects 6-8% of children, and the prevalence is believed to be increasing. The gold standard of food allergy diagnosis is oral food challenges (OFCs) however, they are resource-consuming and potentially dangerous. Skin prick tests (SPTs) are able to detect the presence of allergen-specific IgE antibodies (sensitization), but they have low specificity for clinically significant food allergy. To reduce the need for OFCs, it has been suggested that children forgo an OFC if their SPT wheal size exceeds a cutoff that has a high predictability for food allergy. Although data for these studies are almost always gathered from high-risk populations, the 95% positive predictive values (PPVs) vary substantially between studies. SPT thresholds with a high probability of food allergy generated from these studies may not be generalizable to other populations, because of highly selective s les and variability in participant's age, test allergens, and food challenge protocol. Standardization of SPT devices and allergens, OFC protocols including standardized cessation criteria, and population-based s les would all help to improve generalizability of PPVs of SPTs.
Publisher: Massachusetts Medical Society
Date: 03-03-2011
DOI: 10.1056/NEJMC1100063
Publisher: Elsevier BV
Date: 04-2002
Publisher: Wiley
Date: 03-01-2014
DOI: 10.1002/MDS.25795
Abstract: Friedreich ataxia (FRDA) generally results from reduced frataxin, a mitochondrial protein involved in iron metabolism. We assessed whether HFE p.C282Y and/or p.H63D heterozygosity modifies age at disease onset or disease severity in in iduals with FRDA. One hundred seventy in iduals with FRDA were assessed for the association of HFE p.C282Y and p.H63D with (1) age at disease onset and (2) Friedreich Ataxia Rating Scale (FARS) score. After adjusting for the smaller FXN GAA repeat size and sex, in iduals with FRDA and heterozygous for p.C282Y had disease onset on average 3.72 years earlier than those homozygous for the wild-type amino acid (P = 0.02). Neither mutation affected disease severity as measured by FARS. It is hypothesized that the association between p.C282Y heterozygosity and an earlier age at FRDA onset relates to exacerbation of the already dysregulated iron metabolism that plays a major role in the pathogenesis of FRDA.
Publisher: Wiley
Date: 02-04-2019
DOI: 10.1111/ALL.13767
Abstract: The genetic determinants of food allergy have not been systematically reviewed. We therefore systematically reviewed the literature on the genetic basis of food allergy, identifying areas for further investigation. We searched three electronic databases (MEDLINE, EMBASE and PubMed) on 9 January 2018. Two authors screened retrieved articles for review according to inclusion criteria and extracted relevant information on study characteristics and measures of association. Eligible studies included those that reported an unaffected nonatopic control group, had genetic information and were carried out in children. Of the 2088 studies retrieved, 32 met our inclusion criteria. Five were genome-wide association studies, and the remaining were candidate gene studies. Twenty-two of the studies were carried out in a predominantly Caucasian population with the remaining 10 from Asian-specific populations or unspecified ethnicity. We found FLG, HLA, IL10, IL13, as well as some evidence for other variants (SPINK5, SERPINB and C11orf30) that are associated with food allergy. Little genetic research has been carried out in food allergy, with FLG, HLA and IL13 being the most reproducible genes for an association with food allergy. Despite promising results, existing genetic studies on food allergy are inundated with issues such as inadequate s le size and absence of multiple testing correction. Few included replication analyses or population stratification measures. Studies addressing these limitations along with functional studies are therefore needed to unravel the mechanisms of action of the identified genes.
Publisher: Elsevier BV
Date: 03-2016
Publisher: Elsevier BV
Date: 2013
Publisher: BMJ
Date: 08-2015
Publisher: Wiley
Date: 17-06-2018
DOI: 10.1111/ALL.13408
Abstract: The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JACI.2016.02.014
Abstract: The prevalence of school students at risk of anaphylaxis in Victoria is unknown and has not been previously studied. Similarly, rates of adrenaline autoinjector usage in the school environment have yet to be determined given increasing prescription rates. We sought to determine time trends in prevalence of school children at risk of anaphylaxis across all year levels and the annual usage rate of adrenaline autoinjectors in the school setting relative to the number of students at risk of anaphylaxis. Statewide surveys from more than 1,500 government schools including more than 550,000 students were used and prevalence rates (%) with 95% CIs were calculated. The overall prevalence of students at risk of anaphylaxis has increased 41% from 0.98% (95% CI, 0.95-1.01) in 2009 to 1.38% (95% CI, 1.35-1.41) in 2014. There was a significant drop in reporting of anaphylaxis risk with transition from the final year of primary school to the first year of secondary school, suggesting a change in parental reporting of anaphylaxis risk among secondary school students. The number of adrenaline autoinjectors activated per 1000 students at risk of anaphylaxis ranged from 6 to 8 per year, with consistently higher activation use in secondary school students than in primary school students. Statewide prevalence of anaphylaxis risk has increased in children attending Victorian government schools. However, adrenaline autoinjector activation has remained fairly stable despite known increase in the rates of prescription.
Publisher: Elsevier BV
Date: 02-2018
Publisher: Elsevier BV
Date: 02-2019
Publisher: American Thoracic Society
Date: 09-2012
Publisher: Wiley
Date: 08-09-2010
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.IAC.2011.11.008
Abstract: The rise in food allergy prevalence in developed countries is evident from anecdotal reports but has been difficult to document and until recently good quality prevalence data were lacking. Although most emerging risk factors seem related to the "modern lifestyle" the reasons for the rise in food allergy prevalence remain poorly understood. The incidence of food allergy-related anaphylaxis is rising particularly in children younger than 5 years of age. Emerging studies are better designed to assess the true prevalence of IgE-mediated food allergy using formal population s ling frames, standardized and objective outcome data including use of the gold standard oral food challenge, and the capacity to adjust for potential selection bias.
Publisher: BMJ
Date: 2018
DOI: 10.1136/BMJOPEN-2017-020232
Abstract: Atopic diseases, including food allergy, have become a predominant cause of chronic illness among children in developed countries. In Australia, a rise in hospitalisations among infants coded as anaphylaxis to foods coincided with the replacement of whole-cell pertussis (wP) vaccine with subunit acellular pertussis (aP) vaccine on the national immunisation schedule in the late 1990s. Atopy is characterised by a tendency to mount T helper type 2 (Th2) responses to otherwise innocuous environmental antigens. Compared with infants who receive aP as their first pertussis vaccine, those who receive wP appear less likely to mount Th2 immune responses to either vaccine or extraneous antigens. We therefore speculate that removal of wP from the vaccine schedule contributed to the observed rise in IgE-mediated food allergy among Australian infants. This is a retrospective in idually matched case–control study among a cohort of Australian children born from 1997 to 1999, the period of transition from wP to aP vaccines we include in the cohort children listed on Australia’s comprehensive population-based immunisation register as having received a first dose of either pertussis vaccine by 16 weeks old. 500 cohort children diagnosed as having IgE-mediated food allergy at specialist allergy clinics will be included as cases. Controls matched to each case by date and jurisdiction of birth and regional socioeconomic index will be s led from the immunisation register. Conditional logistic regression will be used to estimate OR (±95% CI) of receipt of wP (vs aP) as the first vaccine dose among cases compared with controls. The study is approved by all relevant human research ethics committees: Western Australia Child and Adolescent Health Services (2015052EP), Women’s and Children’s Hospital (HREC/15/WCHN/162), Royal Children’s Hospital (35230A) and Sydney Children’s Hospital Network (HREC/15/SCHN/405). Outcomes will be disseminated through publication and scientific presentation. NCT02490007 .
Publisher: MDPI AG
Date: 16-12-2013
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JAIP.2019.01.050
Abstract: It is unclear whether early life food sensitization (as opposed to aeroallergen sensitization) is associated with subsequent poor lung function. We investigated the associations between food sensitization in the first 2 years of life and lung function at 12 to 18 years and whether these observed associations are mediated through aeroallergen sensitization or asthma. We used data from a high-risk cohort (Melbourne Atopy Cohort Study [MACS]) and a population-based "Influence of life-style-related factors on the development of the Immune System and Allergies in East and West Germany plus the influence of traffic emissions and genetics" (LISAplus) cohort. Food sensitization was assessed at 6, 12, and 24 months in MACS and 24 months in LISAplus. Lung function was evaluated by spirometry at 12 and 18 years in MACS and 15 years in LISAplus. Linear regression models were used to estimate the association with sensitization (food and/or aeroallergen) while adjusting for potential confounders. Sensitization to food without aeroallergen at 6 months was associated with reduced forced expiratory volume in 1 second (FEV This study showed that food sensitization at 6 and 12 months was associated with reduced FEV
Publisher: Wiley
Date: 16-09-2016
DOI: 10.1111/PAI.12620
Abstract: Food allergy continues to be a significant public health concern for which there are no approved treatments and management strategies primarily include allergen avoidance and pharmacological measures for accidental exposures. Food allergy is thought to result from either a failure to establish oral tolerance or the breakdown of existing oral tolerance, and therefore, experimental preventative and treatment strategies are now aimed at inducing specific oral tolerance. This may occur in infancy prior to the development of food allergy through the optimal timing of dietary exposure (primary oral tolerance induction) or as a treatment for established food allergy through oral immunotherapy (secondary oral tolerance induction). Trials examining the effectiveness of early dietary allergen exposure to prevent food allergy have yielded promising results for peanut allergy but not so for other allergens, although the results of several trials are yet to be published. Although infant feeding guidelines no longer advise to avoid allergenic foods and exposure to food allergens orally is an important step in inducing food tolerance by the immune system, evidence regarding the optimal timing, dose and form of these foods into the infant's diet is lacking. Likewise, oral immunotherapy trials appear promising for inducing desensitization however, the long-term efficacy in achieving sustained desensitization and optimal protocols to achieve this is unknown. More research is needed in this emerging field.
Publisher: Wiley
Date: 21-11-2008
DOI: 10.1111/J.1399-3038.2008.00731.X
Abstract: Several studies have shown differences in the composition of the gastrointestinal flora of children who develop sensitization to food allergens compared with non-allergic children. It has been hypothesized that changes in the gut microbiota resulting from caesarean section delivery could increase a child's risk of developing food allergy however, studies examining the relationship between mode of delivery and food allergy have produced conflicting results. The objective of this review was to determine whether there is sufficient evidence to support an association between delivery by caesarean section and the development of sensitization to food allergens and immunoglobulin E (IgE) mediated food allergy. Using predefined inclusion and exclusion criteria, MEDLINE and PubMed were searched for studies investigating the relationship between caesarean section delivery and food allergy. The information on the quality of the studies and results were extracted and analysed systematically. The search identified four relevant studies as per our protocol. Symptomatic food allergy was used as the outcome in two studies and was found to occur more frequently in children born by caesarean section in one study while the second study found no association between food allergy diagnoses and mode of delivery. The other two studies measured levels of food antigen-specific IgE, with both studies showing an increase in sensitization to food allergens among children born by caesarean section. Overall, there is evidence that the risk of developing IgE-mediated sensitization to food allergens is increased among children delivered by caesarean section, however further studies using objectively diagnosed food allergy as the outcome are needed to verify whether this equates to an increase in confirmed food allergy. Future birth cohort studies should control for the effects of mode of delivery when investigating environmental modifiers of food allergy.
Publisher: Elsevier BV
Date: 2013
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.PCL.2015.07.005
Abstract: Australia has reported the highest rates of food allergy, using the gold standard, oral food challenge. This phenomenon, which appears linked to the "modern lifestyle" and has coincided with the explosion of the new diseases of affluence in the 21st century, dubbed "affluenza," has spurred a multitude of theories and academic investigations. This review focuses on potentially modifiable lifestyle factors for the prevention of food allergy and presents the first data to emerge in the Australian context that centers around the dual allergen exposure hypothesis, the vitamin D hypothesis, and the hygiene hypothesis.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.COI.2016.05.005
Abstract: The rise in IgE-mediated food allergy in recent times is the likely result of gene-environment interactions mediated via epigenetic pathways. As epigenetic modifications, including DNA methylation, are at the interface between the environment and the genome, they may be ideal biomarkers of modifiable disease pathways. High-throughput methylation profiling of immune cell subtypes or whole blood from patients allows the identification of disease specific epigenetic variants. If faithfully tracking with disease parameters, these 'signatures' may have clinical applications as biomarkers of disease or therapeutic response. Development of such tools will depend on a number of factors, including determining the most appropriate experimental approach, analysis methodology, patient groups, and informative target cells/tissues. Here we discuss these potential applications and their implications for food allergy practise.
Publisher: Springer Science and Business Media LLC
Date: 29-11-2007
DOI: 10.1007/S10534-006-9038-7
Abstract: Wilson's disease carriers constitute 1% of the human population. It is unknown whether Wilson's disease carriers are at increased susceptibility to copper overload when exposed to chronically high levels of ingested copper. This study investigated the effect of chronic excess copper in drinking water on the heterozygous form of the Wilson's disease mouse model--the toxic milk (tx) mouse. Mice were provided with drinking water containing 300 mg/l copper for 4-7, 8-11, 12-15 or 16-20 months. At the completion of the study liver, spleen, kidney and brain tissue were analyzed by atomic absorption spectroscopy to determine copper concentration. Plasma ceruloplasmin oxidase activity and liver histology were also assessed. Chronic copper loading resulted in significantly increased liver copper in both tx heterozygous and tx homozygous mice, while wild type mice were resistant to the effects of copper loading. Copper loading effects were greatest in tx homozygous mice, with increased extrahepatic copper deposition in spleen and kidney - an effect absent in heterozygote and wild type mice. Although liver histology in homozygous mice was markedly abnormal, no histological differences were noted between heterozygous and wild type mice with copper loading. Tx heterozygous mice have a reduced ability to excrete excess copper, indicating that half of the normal liver Atp7b copper transporter activity is insufficient to deal with large copper intakes. Our results suggest that Wilson's disease carriers in the human population may be at increased risk of copper loading if chronically exposed to elevated copper in food or drinking water.
Publisher: Wiley
Date: 16-09-2016
DOI: 10.1111/PAI.12619
Publisher: Wiley
Date: 04-11-2016
DOI: 10.1111/ALL.12784
Abstract: There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9 95% CI 2.0-4.0), eczema (pooled OR 2.7 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1 95% CI 1.9-4.9) from 4 to 8 years. Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-01-2016
DOI: 10.1126/SCITRANSLMED.AAD4322
Abstract: Infants who develop food allergy display hyperresponsive innate immunity at birth that promotes nonclassical T H 2 differentiation.
Publisher: Elsevier BV
Date: 08-2002
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2010
Publisher: Wiley
Date: 09-2009
DOI: 10.1111/J.1440-1754.2009.01546.X
Abstract: Cow's milk protein allergy is a condition commonly managed by general practitioners and paediatricians. The diagnosis is usually made in the first 12 months of life. Management of immediate allergic reactions and anaphylaxis includes the prevention of accidental food ingestion and provision of an adrenaline autoinjector, if appropriate. By contrast, the clinical course of delayed food-allergic manifestations is characterised by chronicity, and is often associated with nutritional or behavioural sequelae. Correct diagnosis of these non-IgE-mediated conditions may be delayed due to a lack of reliable diagnostic markers. This review aims to guide clinicians in the: (i) diagnostic evaluation (skin prick testing or measurement of food-specific serum IgE levels indications for diagnostic challenges for suspected IgE- and non-IgE-mediated food allergy), (ii) dietary treatment, (iii) assessment of response to treatment, (iv) differential diagnosis and further diagnostic work-up in non-responders, (v) follow-up assessment of tolerance development and (vi) recommendations for further referral.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2008
DOI: 10.1002/LT.21443
Abstract: Liver cell transplantation in humans has been impeded by invariable loss of the graft. It is unclear whether graft loss is due to an immune response against donor hepatocytes. Transplantation with ABO-matched liver cells was performed in a patient with Crigler-Najjar type 1. After successful engraftment, there was a gradual loss of graft function. Solid-phase enzyme immunoassay testing and cell-complement cytotoxicity assays detecting preformed antibodies directed toward class I and/or class II human leukocyte antigen (HLA) molecules were negative. In contrast, a striking host alloresponse to either the HLA-B39 or C7 antigen was found, suggesting that a vigorous response to a defined mismatched HLA antigen contributed to graft loss in our patient. This study provides evidence that a T-cell-mediated immune mechanism could be responsible for human liver cell transplant graft loss. This finding warrants confirmation in future liver cell transplants in humans.
Publisher: Informa UK Limited
Date: 2013
DOI: 10.1586/ECI.12.80
Abstract: Hydrolyzed formulae are created by using enzymatic processes to break native proteins into smaller fragments. They may prevent development of allergic diseases by reducing exposure to intact allergens. Partially hydrolyzed whey formula (pHWF) is particularly promising for allergy prevention, as it is cheap to manufacture and palatable. Scientific organizations have recommended the use of hydrolyzed formula in the first 4-6 months of life for the prevention of allergic disease based on a limited number of trials. Three recent developments challenge these recommendations: our growing understanding of the importance of allergen exposure for induction of immune tolerance, recently published evidence that failed to identify a protective effect of pHWF, which the authors and other experts believe will necessitate updating of systematic reviews, and methodological limitations of available trials and systematic reviews on which these recommendations are based. Until more definitive evidence is obtained, the authors recommend continuing to advocate that 'breast is best', and caution against overstating the potential for pHWF to prevent allergic disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-11-2009
DOI: 10.1002/HEP.23448
Publisher: Informa UK Limited
Date: 17-01-2017
DOI: 10.1080/02770903.2016.1253730
Abstract: Early life tobacco smoke exposure may influence asthma, lung function and lung function growth into adolescence. We aimed to determine the associations between perinatal smoke exposure and asthma and lung function up to 18 years of age. We prospectively recorded perinatal parental smoking and measured respiratory outcomes at 12 and 18 years in the Melbourne Atopy Cohort Study (MACS), a longitudinal birth cohort. Multiple logistic regression was used to analyse the associations between perinatal smoke exposure and asthma at 12 (n = 370) and 18 years (n = 411). Multiple linear regression was used to investigate the relationship between perinatal smoking and: lung function (12 and 18 years) and lung function growth (between 12 and 18 years). At 18 years, girls exposed to parental smoking during the perinatal period had increased odds of asthma (OR: 3.45, 95%CI: 1.36, 8.77), reduced pre-bronchodilator Forced expiratory volume in one-second (FEV Perinatal smoke may affect risk of asthma, reduce lung function and lung function growth in adolescence. Girls appear to be more susceptible than boys.
Publisher: Wiley
Date: 29-11-2020
DOI: 10.1111/JPC.14666
Abstract: The implementation of a sugar tax in Australia has been discussed extensively as a way to combat rising rates of obesity and diabetes. We aim to review international efforts by governments to implement sugar tax initiatives. We summarise the different initiatives and investigate their pros and cons, evidence of impact and what the possibilities are for introducing a sugar tax in the Australian context. We conclude that government-imposed sugar taxes on production reduce sugar consumption in the general population. It remains unclear whether the reduction in sugar has generally led to a reduction in population obesity. Nonetheless, the fact that commercial actors have themselves begun to reduce sugar in their products indicates that they are aware of the benefits of reduced sugar consumption in the community, if only by way of changing consumer preferences.
Publisher: Wiley
Date: 28-05-2013
DOI: 10.1111/CEA.12048
Abstract: A variety of hypotheses have been proposed to explain the recently described increase in food allergy among children living in developed countries. In this study, we summarize the emerging risk factors for IgE-mediated food allergy in early life, and then review the evidence for and against an association between low vitamin status (VDS) and food allergy. We consider whether each of the epidemiological variables that have been associated with food allergy may also be associated with VDS and argue that future studies must adequately account for the potential relationships between risk factors for food allergy and VDS, and must also discriminate between vitamin D derived by sun exposure, diet and oral supplementation.
Publisher: Wiley
Date: 20-02-2011
DOI: 10.1111/J.1399-3038.2011.01145.X
Abstract: Food allergy is a substantial and evolving public health issue, recently emerging over the last 10-15 yr as a 'second wave' of the allergy epidemic. It remains unclear why this new phenomenon has lagged decades behind the 'first wave' of asthma, allergic rhinitis and inhalant sensitization. In regions like Australia, which lead the respiratory epidemic, challenge-proven IgE-mediated food allergy now affects up to 10% of infants. Although their parents were among the first generation to experience the large-scale rise in allergic diseases, disorders of oral tolerance were previously uncommon. Of further concern, this new generation appears less likely to outgrow food allergy than their predecessors with long-term implications for disease burden. Allergic disease has been linked to the modern lifestyle including changing dietary patterns, changing intestinal commensal bacteria and vehicular pollution. It is not yet known whether the rise in food allergy is a harbinger of earlier and more severe effects of these progressive environmental changes or whether additional or unrelated lifestyle factors are implicated. New studies suggest environmental factors can produce epigenetic changes in gene expression and disease risk that may be potentially heritable across generations. The rising rates of maternal allergy, a strong direct determinant of allergic risk, could also be lifying the effect of environmental changes. Preliminary evidence that non-Caucasian populations may be even more susceptible to the adverse effects of 'westernisation' has substantial global implications with progressive urbanization of the more populous regions in the developing world. Unravelling the environmental drivers is critical to curtail a potential tsunami of allergic disease.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Wiley
Date: 24-03-2017
DOI: 10.1111/JGH.13621
Publisher: Wiley
Date: 03-04-2019
DOI: 10.1111/CEA.13383
Abstract: An infant's age at introduction of complementary solids may contribute to food allergy. We aimed to synthesize the literature on the association between age at introduction of complementary solids, excluding milk products, and food allergy and sensitization. We searched the electronic databases PubMed and EMBASE (January 1946-February 2017) using solid food, allergy and sensitization terms. Two authors selected papers according to inclusion criteria, identifying 16 cohort studies, 1 case-control study and 8 randomized controlled trials (RCTs). Pooled effects across studies were estimated using random-effects meta-analysis. Cohort studies-Introducing complementary solids at age ≥ 4 months vs <4 months was not associated with food allergy (OR 1.22 95% CI, 0.76-1.96) but was associated with food sensitization (OR 1.93 95% CI 1.57-2.38). First exposure from age 4 to 6 months vs <4 months was not associated with food allergy (OR 1.01 95% CI, 0.64-1.60) but was associated with food sensitization (OR 2.46 95% CI 1.55-3.86). Randomized controlled trials-Egg exposure from age 4 months was associated with reduced egg allergy (OR 0.63, 95% CI, 0.44-0.90) and sensitization (OR 0.76, 95% CI, 0.51-0.95). Peanut exposure from age 4 months compared to delayed exposure was associated with reduced peanut allergy (OR 0.28, 95% CI 0.14-0.57). We found no evidence from observational studies that introducing solids before 4 months protected against food allergy, but there was evidence for protection against food sensitization. From RCTs, introducing egg from 4 to 6 months and peanut from 4 to 11 months reduced the risk of egg allergy, peanut allergy and egg sensitization. PROSPERO systematic review registry (CRD42016033473).
Publisher: Wiley
Date: 23-04-2018
DOI: 10.1111/CEA.13140
Abstract: Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non-allergenic) and development of eczema has not previously been systematically reviewed. PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta-analyses were performed after grouping studies according to the age and type of exposure. A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, 2 case-controls, 1 cross-sectional study and 2 randomized controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema. The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema.
Publisher: Bentham Science Publishers Ltd.
Date: 02-07-2015
DOI: 10.2174/1389557515666150519111328
Abstract: Studies from several countries have reported an association between latitudes further from the equator and proxy markers of food allergy prevalence. As latitudes further from the equator are associated with lower sun exposure and vitamin D status (VDS), it has been proposed that low VDS may be a risk factor for food allergy. A range of basic science evidence supports the biological plausibility of this hypothesis and recent work has identified a cross sectional association between low VDS and challenge proven food allergy in infants. Overall, however, the evidence regarding the relationship between VDS and food allergy remains controversial and the limited longitudinal data are discouraging. In this review we consider the evidence for and against low VDS as a risk factor for food allergy and discuss the possibility that other factors (including genetic variables) may contribute to the inconsistent nature of the available observational evidence. We then discuss whether genetic and/or environmental factors may modify the potential influence of VDS on food allergy risk. Finally, we argue that given the rising burden of food allergy, the balance of available evidence regarding the potential relevance of VDS to this phenomenon, and the inherent limitations of the existing observational data, there is a compelling case for conducting randomised clinical trials of vitamin D supplementation for the prevention of food allergy during early life.
Publisher: Elsevier
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 04-04-2012
Publisher: Wiley
Date: 05-06-2014
DOI: 10.1111/ALL.12417
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JAIP.2017.12.025
Abstract: Precautionary allergen labeling (PAL) also known as "may contain" labeling has been applied to many packaged food products around the world. PAL is a voluntary form of labeling whose original intent was to help ensure that packaged foods were as safe as possible for allergic consumers by alerting them to the possible presence of allergen residues resulting from the use of shared processing equipment, shared processing facilities, or other industry practices. However, the proliferation of PAL and the myriad of various phrasing used as PAL statements are confusing to consumers and serve to diminish their quality of life. Thus many allergic consumers are known to ignore PAL statements. Analytical surveys indicate that many PAL products contain no detectable allergen residues and are likely safe for allergic consumers. However, up to 8% of allergic consumers report having had reactions to the ingestion of PAL products. Clearly a better approach to labeling is needed that balances the health and safety considerations of allergic consumers with their desire to enjoy the widest possible array of foods available in the marketplace. This article presents an overview and discussion of the shortcomings of the current PAL system and explores why a new approach is required.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2016
Publisher: Walter de Gruyter GmbH
Date: 10-01-2019
Abstract: Dried blood spot (DBS) s le applications now encompass analytes related to clinical diagnosis, epidemiological studies, therapeutic drug monitoring, pharmacokinetic and toxicokinetic studies. Haematocrit (Hct) and haemoglobin (Hb) at very high or low concentrations may influence the accuracy of measurement quantification of the DBS s le. In this study, we aimed to predict the Hct of the punched DBS through primary spectrophotometric estimation of its haemoglobin-derivative (Hb-drv) content. Formic acid solution was used to elute Hb-drv content of 3.2 mm spotted blood from its dry matrix. Direct spectrometry measurement was utilised to scan the extracted Hb-drv in the visible spectrum range of 520–600 nm. The linear relationship between an in idual’s Hct percentage and Hb-drv concentration was applied to estimate the Hct level of the blood spot. De-identified whole blood s les were used for the method development and evaluation studies. The Hb-drv estimation is valid in s les months old. Method validation experiments DBS demonstrate linearity between 82.5 and 207.5 g/L, average coefficient of variation of 3.6% (intra-assay) and 7.7% (inter-assay), analytical recovery of 84%, and a high positive correlation ( r =0.88) between Hb-drv and the original whole blood Hct. The Bland-Altman difference plot demonstrates a mean difference of 2.4% between the calculated DBS Hct and the directly measured Hct from fresh whole bloods. We have successfully developed a simple Hb-drv method to estimate Hct in aged DBS s les. This method can be incorporated into DBS analytical work-flow for the in-situ estimation of Hct and subsequent correction of the analyte of interest as required.
Publisher: Massachusetts Medical Society
Date: 17-01-2008
DOI: 10.1056/NEJMOA073286
Publisher: Wiley
Date: 14-10-2016
DOI: 10.1111/PAI.12480
Abstract: Longitudinal data on the natural history of food sensitization beyond early childhood are scarce. We aimed to investigate the natural history of milk, egg and peanut sensitization from infancy to 18 years and assess whether early food sensitization predicted adolescent food allergy. Sensitization to cow's milk, hen's egg and peanut was measured by skin prick testing at ages 6 months, 1, 2, 12 and 18 years in a high-risk allergy birth cohort (n = 620). Generalized additive models investigated interactions with sex, eczema and aeroallergen sensitization in infancy. Logistic regression assessed the relationships between early food sensitization and adolescent sensitization and probable food allergy up to 18 years. The prevalence of egg and peanut sensitization peaked at 12 months, while milk sensitization peaked at both 1 and 12 years. Boys with early eczema had the highest prevalences of milk and egg sensitization throughout follow-ups. However, neither sex nor eczema influenced the prevalence of peanut sensitization over time. New onset food sensitization beyond the age of 2 was observed in 7% of participants. Food sensitization at 12 months was associated with increased risk of adolescent food sensitization and adolescent probable food allergy, with sensitization to more than one food allergen had the strongest predictor. Food sensitization prevalence is highest in infancy and declines after 12 months of age. Boys with early-life eczema have the highest prevalence of milk and egg sensitization. Food sensitization at 12 months can predict children at greater risk of adolescent sensitization and probable food allergy at 12 and 18 years.
Publisher: BMJ
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 27-02-2002
Abstract: The serum activity of the hepatic enzyme gamma-glutamyl transferase (GGT) is elevated in the newborn relative to older age groups. Few reports to date have studied the influence of perinatal factors on neonatal serum GGT and no study has assessed the influence of maternal drug ingestion. Cord blood was randomly collected from 234 liveborn infants and correlated with a range of maternal and fetal perinatal variables to assess influences on cord blood GGT. Our study showed that the range of cord blood GGT activity in 234 randomly selected term newborns was 22 to 556 IU/l. In a subgroup of 75 newborns, GGT activity was independently influenced by only two of the variables studied - cocaine exposure and fetal gender (p=0.009, r=0.39). Females had a lower GGT than males (95+/-66 vs 130+/-90 IU/l, p<0.001) while GGT activity in cocaine-exposed newborns was lower than in cocaine-nonexposed newborns (96+/-48 vs 142+/-109, p<0.01). Birth weight, race, gestational age, and maternal serum GGT were not found to significantly influence cord blood GGT activity. Maternal GGT was uniformly normal and was not affected by any of the variables tested. Our findings demonstrate that the reference range for cord blood GGT activity is wide and appears to be influenced by fetal gender and cocaine exposure.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JAIP.2016.09.020
Abstract: Mandatory labeling of products with top allergens has improved food safety for consumers. Precautionary allergen labeling (PAL), such as "may contain" or "manufactured on shared equipment," are voluntarily placed by the food industry. To establish knowledge of PAL and its impact on purchasing habits by food-allergic consumers in North America. Food Allergy Research & Education and Food Allergy Canada surveyed consumers in the United States and Canada on purchasing habits of food products featuring different types of PAL. Associations between respondents' purchasing behaviors and in idual characteristics were estimated using multiple logistic regression. Of 6684 participants, 84.3% (n = 5634) were caregivers of a food-allergic child and 22.4% had food allergy themselves. Seventy-one percent reported a history of experiencing a severe allergic reaction. Buying practices varied on the basis of PAL wording 11% of respondents purchased food with "may contain" labeling, whereas 40% purchased food that used "manufactured in a facility that also processes." Twenty-nine percent of respondents were unaware that the law requires labeling of priority food allergens. Forty-six percent were either unsure or incorrectly believed that PAL is required by law. Thirty-seven percent of respondents thought PAL was based on the amount of allergen present. History of a severe allergic reaction decreased the odds of purchasing foods with PAL. Almost half of consumers falsely believed that PAL was required by law. Up to 40% surveyed consumers purchased products with PAL. Understanding of PAL is poor, and improved awareness and guidelines are needed to help food-allergic consumers purchase food safely.
Publisher: Wiley
Date: 06-03-2019
DOI: 10.1111/ALL.13732
Abstract: Despite an increasing number of publications from in idual countries and regions, there is still no systematic review of the global epidemiology of anaphylaxis in the general paediatric population. We conducted a systematic review, using a protocol registered and published with the international prospective register of systematic reviews (PROSPERO). Results were reported following PRISMA guidelines. The search strategy was designed in Medline (ovid) and modified for Embase (ovid) and PubMed. Papers were screened by two independent reviewers following selection and exclusion criteria. Data extraction and risk of bias assessment were completed by the same two reviewers. Studies in adults only or those that did not report data in children separately were excluded. A final total of 59 articles were included. Of these, 5 reported cumulative incidence, 39 reported incidence rate and 17 reported prevalence data. The incidence of anaphylaxis in children worldwide varied widely, ranging from 1 to 761 per 100 000 person-years for total anaphylaxis and 1 to 77 per 100 000 person-years for food-induced anaphylaxis. The definition of anaphylaxis from NIAID/FAAN was the most commonly used. Gender and ethnicity were demographic risk factors associated with anaphylaxis in children. Increasing total or food-induced anaphylaxis incidence over time was reported by 19 studies. The reported incidence of anaphylaxis in children varied widely. Studies in developing countries are underrepresented. To accurately compare anaphylaxis incidence between countries and investigate the time trends, further studies using a standardized definition across different countries are required.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2018
DOI: 10.1038/NRDP.2017.98
Abstract: Food allergies manifest in a variety of clinical conditions within the gastrointestinal tract, skin and lungs, with the most dramatic and sometimes fatal manifestation being anaphylactic shock. Major progress has been made in basic, translational and clinical research, leading to a better understanding of the underlying immunological mechanisms that lead to the breakdown of clinical and immunological tolerance against food antigens, which can result in either immunoglobulin E (IgE)-mediated reactions or non-IgE-mediated reactions. Lifestyle factors, dietary habits and maternal-neonatal interactions play a pivotal part in triggering the onset of food allergies, including qualitative and quantitative composition of the microbiota. These factors seem to have the greatest influence early in life, an observation that has led to the generation of hypotheses to explain the food allergy epidemic, including the dual-allergen exposure hypothesis. These hypotheses have fuelled research in preventive strategies that seek to establish desensitization to allergens and/or tolerance to allergens in affected in iduals. Allergen-nonspecific therapeutic strategies have also been investigated in a number of clinical trials, which will eventually improve the treatment options for patients with food allergy.
Publisher: Wiley
Date: 20-04-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
Publisher: Oxford University Press (OUP)
Date: 2018
Abstract: Food allergies are increasing globally, including numbers of allergens, the sensitization rate, and the prevalence rate. To protect food-allergic in iduals in the community, food allergies need to be appropriately managed. This paper describes current Australian food allergen management practices. In Australia, the prevalence of food allergies, the anaphylaxis rate, and the fatal anaphylaxis rate are among the highest in the world. Interagency and stakeholder collaboration is facilitated and enhanced as Australia moves through past, current, and ongoing food allergen challenges. As a result, Australia has been a global leader in regulating the labeling of common allergens in packaged foods and their disclosure in foods not required to bear a label. Moreover, the food industry in Australia and New Zealand has developed a unique food allergen risk management tool, the Voluntary Incidental Trace Allergen Labelling program, which is managed by the Allergen Bureau. This paper summarizes insights and information provided by the major stakeholders involved to protect food-allergic consumers from any allergic reaction. Stakeholders include government consumer protection, regulation, and enforcement agencies the food industry and food allergen testing and food allergen/allergy research bodies in Australia. The ongoing goal of all stakeholders in food allergen management in Australia is to promote best practice food allergen management procedures and provide a wide choice of foods, while enabling allergic consumers to manage their food allergies and reduce the risk of an allergic reaction.
Publisher: Wiley
Date: 07-04-2021
DOI: 10.1111/ALL.14823
Abstract: In Western countries, Asian children have higher food allergy risk than Caucasian children. The early‐life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia. We studied children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 878) and children of Asian ancestry in the HealthNuts cohort (n = 314). Food allergy was defined as a positive SPT ≥3 mm to egg or peanut AND either a convincing history of IgE‐mediated reaction at 18 months (GUSTO) or a positive oral food challenge at 14‐18 months (HealthNuts). Eczema was defined as parent‐reported doctor diagnosis. Food allergy prevalence was 1.1% in Singapore and 15.0% in Australia ( P .001). Egg introduction was more often delayed ( months) in Singapore (63.5%) than Australia (16.3% P .001). Prevalence of early‐onset eczema ( months) was lower in Singapore (8.4%) than Australia (30.5%) ( P .001). Children with early‐onset eczema were more likely to have food allergy than those without eczema in Australia [aOR 5.11 (2.34‐11.14) P .001] and Singapore [aOR4.00 (0.62‐25.8) P = 0.145]. Among Asian children, prevalence of early‐onset eczema and food allergy was higher in Australia than Singapore. Further research with larger s le sizes and harmonized definitions of food allergy between cohorts is required to confirm and extend these findings. Research on environmental factors influencing eczema onset in Australia and Singapore may aid understanding of food allergy pathogenesis in different parts of the world.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JACI.2015.05.051
Abstract: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype high, the GG genotype). Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7 95% CI, 0.2-2.0 P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6 95% CI, 1.5-106.6), particularly in those with the GG genotype. Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.
Publisher: MDPI AG
Date: 04-11-2013
Publisher: Springer Science and Business Media LLC
Date: 20-03-2008
Publisher: Wiley
Date: 09-01-2020
DOI: 10.1111/ALL.13979
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.JACI.2007.11.024
Abstract: Understanding predictors of clinical remission would assist in clinical management of peanut allergy. We sought to determine the early clinical predictors of peanut allergy remission using a longitudinal cohort of young children with peanut allergy. Consecutive patients less than 2 years of age with peanut allergy were identified on the basis of skin prick test (SPT) wheal size of 95% positive predictive value or greater. Baseline SPT responses to peanuts, tree nuts, and sesame and serum peanut-specific IgE antibody levels were documented, and follow-up studies were conducted at 1- to 2-year intervals for up to 8 years. Peanut food challenges were performed when SPT responses decreased to less than the 95% positive predictive value for peanut allergy. SPT wheal diameters to peanut extract of 6 mm or greater (hazard ratio, 2.16 95% CI, 1.23-3.786 P = .008) and peanut-specific IgE antibody of 3 kUA/L or greater (hazard ratio, 2.74 95% CI, 1.13-6.61 P = .025) before the age of 2 years were independent predictors of persistent peanut allergy. Mean SPT wheal diameters of nonremitters increased (r = 0.31, P < .001), whereas those of remitters decreased (r = -0.26, P = .002) between 1 and 4 years of age. Twenty-one percent of young children with peanut allergy became clinically tolerant by age 5 years. Remission of peanut allergy can be predicted by low levels of IgE antibodies to peanut in the first 2 years of life or decreasing levels of IgE sensitization by the age of 3 years.
Publisher: Informa UK Limited
Date: 10-09-2015
DOI: 10.1586/17474124.2015.1084873
Abstract: The rates of IgE-mediated food allergy have increased globally, particularly in developed countries. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, suggesting that environmental exposures that alter the immune response play an important role. Genetic factors may also be used to predict an increased predisposition to these environmental risk factors, giving rise to the concept of gene-environment interactions, whereby differential risk of environmental exposures is mediated through the genome. Increasing evidence also suggests a role for epigenetic mechanisms, which are sensitive to environmental exposures, in the development of food allergy. This paper discusses the current state of knowledge regarding the environmental and genetic risk factors for food allergy and how environmental exposures may interact with immune genes to modify disease risk or outcome.
Publisher: Wiley
Date: 12-2019
DOI: 10.1111/CEA.13516
Abstract: Food allergy affects a small but important number of children and adults. Much of the morbidity associated with food allergy is driven by the fear of a severe reaction and fatalities continue to occur. Foods are the commonest cause of anaphylaxis. One of the aims of the European Union-funded Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) project was to improve the identification and management of children and adults at risk of experiencing a severe reaction. A number of interconnected studies within the project have focused on quantifying the severity of allergic reactions the impact of food matrix, immunological factors on severity of reactions the impact of co-factors such as medications on the severity of reactions utilizing single-dose challenges to understand threshold and severity of reactions and community studies to understand the experience of patients suffering real-life allergic reactions to food. Associated studies have examined population thresholds and co-factors such as exercise and stress. This paper summarizes two workshops focused on the severity of allergic reactions to food. It outlines the related studies being undertaken in the project indicating how they are likely to impact on our ability to identify in iduals at risk of severe reactions and improve their management.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2010
DOI: 10.1002/HEP.23786
Publisher: Wiley
Date: 26-12-2015
DOI: 10.1111/CEA.12424
Publisher: Walter de Gruyter GmbH
Date: 24-11-2019
Publisher: Wiley
Date: 12-2013
DOI: 10.1111/PAI.12138
Publisher: Wiley
Date: 23-11-2015
DOI: 10.1111/PAI.12498
Abstract: Regulatory T cells (Tregs) are critical for development of oral tolerance, and studies suggest that dysfunction of Tregs may lead to food allergy. However, to date, no study has investigated Treg responses following in vivo exposure to peanut or egg allergens in humans. To examine changes in peripheral blood CD4(+) CD25(+) Foxp3(+) Treg populations (total, activated and naive) in food-allergic, food-sensitized but tolerant, and healthy (non-sensitized non-allergic) patients over time following in vivo allergen exposure. A subset of infants from the HealthNuts study with egg or peanut allergy (n = 37), egg or peanut sensitization (n = 35), or who were non-sensitized non-allergic (n = 15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMCs were obtained within 1 h of OFC (in vivo allergen exposure), and Treg populations enumerated ex vivo on day 0, and after 2 and 6 days rest in vitro. Non-allergic infants showed stable total Treg frequencies over time food-sensitized infants had a transient fall in Treg percentage with recovery to baseline by day 6 (6.87% day 0, 5.27% day 2, 6.5% day 6) and food-allergic infants showed persistent reduction in Treg (6.85% day 0, 5.4% day 2, 6.2% day 6) following in vivo allergen exposure. Furthermore, food-allergic infants had a significantly lower ratio of activated Treg:activated T cells (10.5 ± 0.77) at day 0 compared to food-sensitized (14.6 ± 1.24) and non-allergic subjects (16.2 ± 1.23). Our data suggest that the state of allergen sensitization is associated with depletion of Treg following allergen exposure. Impaired capacity to regenerate the Treg pool following allergen exposure may be an important factor that determines clinical allergy vs. sensitization without allergic reaction.
Publisher: Springer Science and Business Media LLC
Date: 17-08-2018
DOI: 10.1038/S41467-018-05608-4
Abstract: Food allergy poses a significant clinical and public health burden affecting 2–10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic ( RPTOR , PIK3D , MAPK1 , FOXO1 ) and inflammatory genes ( IL1R , IL18RAP , CD82 ) underpins this suboptimal response. Infants who fail to resolve food allergy in later childhood exhibit cumulative increases in epigenetic disruption at T cell activation genes and poorer lymphoproliferative responses compared to children who resolved food allergy. Our data indicate epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex, and likely reflects pathways modified by gene–environment interactions in food allergy.
Publisher: CRC Press
Date: 22-07-2013
DOI: 10.1201/B15358-3
Publisher: Elsevier BV
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 23-03-2014
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.JACI.2013.11.019
Abstract: 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.
Publisher: Oxford University Press (OUP)
Date: 12-2018
DOI: 10.1111/BJD.15747
Publisher: Informa UK Limited
Date: 27-02-2015
DOI: 10.3109/02770903.2014.1001904
Abstract: Indoor environment factors have been associated with risk of asthma exacerbations in children but little is known about their role on asthma hospital readmissions. As children in Western societies continually spend more time indoors, understanding the influence of these factors on asthma exacerbation is important. We examined the role of indoor environmental and lifestyle characteristics on child asthma readmissions. A hospital-based case-control study recruited 22 children readmitted for asthma and 22 controls not readmitted for asthma. Logistic regression models were used to examine the association between aeroallergens and fungi in the bedroom and indoor lifestyle characteristics factors for asthma readmissions. To determine the best possible set of predictors among a large set of risk factors, we used random forests (RF) techniques. Higher levels of airborne Cladosporium and yeast in the child's bedroom increased risk of readmission (OR = 1.68, 95% CI 1.04-2.72 and OR = 1.52, 95% CI 0.99-2.34, respectively). Carpeted floors in the bedroom and synthetic doonas were also associated with increase in asthma readmissions (OR = 4.07, 95% CI 1.03-16.06 and OR = 14.6, 95% CI 1.26-169.4, respectively). In the home, frequent vacuuming using bagged cleaners increased risk of asthma readmission OR = 15.7 (95% CI 2.82-87.2). Factors in the child's bedroom play an important role in increasing the risk of asthma hospital readmissions. These findings have major clinical implications as the identified potential risk factors may be modifiable. Further epidemiological studies with larger s les are necessary to evaluate these associations further.
Publisher: Wiley
Date: 07-12-2005
DOI: 10.1111/J.1399-0004.2004.00389.X
Abstract: Carrier screening to provide reproductive options has been offered to students in the school setting for a number of years however, genetic susceptibility screening for disease predisposition has not been introduced to the school community. Experience has shown that the success of a population-based programme relies on the community's acceptance. Therefore, we sought to establish the Australian secondary school community's attitudes towards genetic susceptibility screening in schools, with hereditary haemochromatosis as the model condition with an available prevention. School students, aged 15-18 (n = 748), completed a questionnaire immediately before and following an oral educational presentation. Their parents (n = 179) and staff (n = 89) received written information and returned a questionnaire by post. Semi-structured interviews were with Government representatives. Attitudes towards genetic screening in schools and knowledge of genetic and clinical features of haemochromatosis, as well as the likelihood of accepting a genetic susceptibility test for haemochromatosis, were all measured. Participants were positive about genetic screening for disease susceptibility in schools. Their knowledge was high following education with no significant differences between participants of each group. Sixty-eight percent of students would be likely to have the test if it were offered, with parents and staff, indicating that they would like the students to be offered a test, on average. Genetic susceptibility screening in schools is a novel concept. The results of our study indicate that it could be a public health success with the support of the community.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2015
Publisher: Oxford University Press (OUP)
Date: 30-05-2013
DOI: 10.1093/CID/CIT351
Publisher: BMJ
Date: 15-01-2000
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.FCT.2013.10.032
Abstract: In 2011, an expert panel was assembled to establish appropriate Reference Doses for allergenic food residues as a part of the VITAL (Voluntary Incidental Trace Allergen Labeling) program of The Allergen Bureau of Australia & New Zealand (ABA). These Reference Doses would guide advisory labeling decisions for use on food labels. In idual NOAELs and LOAELs were obtained from clinical challenges of food-allergic subjects. Statistical dose-distribution models (log-normal, log-logistic, Weibull) were applied to the in idual NOAELs and LOAELs for each allergenic food. The Reference Doses, in terms of mg of total protein from the allergenic food, were based upon either the ED01 (for peanut, cow's milk), the 95% lower confidence interval of the ED05 (for wheat, soybean, cashew, shrimp, sesame seed, mustard, and lupine), or both (egg, hazelnut) using all appropriate statistical dose-distribution models. Reference Doses were established for 11 allergenic foods ranging from 0.03 mg for egg protein to 10mg for shrimp protein. Reference Doses were not established for fish or celery due to poor model fits with existing data. Reference Doses were not established for other tree nuts beyond hazelnut and cashew because of the absence of data on NOAELs and LOAELs from in idual subjects.
Publisher: Wiley
Date: 11-2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2017
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.JPEDS.2007.04.070
Abstract: Because community-based studies, which report IgE food sensitization (IgE-FS) in more than 80% of infants with moderate atopic eczema, may be influenced by referral bias, we assessed the prevalence of IgE-FS in a cohort of infants with moderate atopic eczema attending a dermatology department clinic. Consecutive infants (n = 51, 39 males median age, 34 weeks range, 20 to 51 weeks) with moderate atopic eczema referred to a university-affiliated dermatology department were studied prospectively. Clinical history and eczema severity were documented. IgE-FS was assessed by the skin prick test (SPT n = 51) and food-specific serum IgE antibodies (CAP-FEIA test n = 41). IgE-FS was diagnosed if the SPT or CAP-FEIA level exceeded the >95% predictive reference cutoff for positive food challenges. Based on SPT, 44 of 51 infants (86% 95% confidence interval [CI] = 74% to 94%) had IgE-FS (cow's milk, 16% egg, 73% peanut, 51%). Using age-specific 95%-predictive cutoff values, CAP-FEIA identified 34 of 41 infants (83% 95% CI = 68% to 93%) with IgE-FS (cow's milk, 23% egg, 80%). Forty-six (90%) infants had IgE-FS to at least 1 food item by either SPT or CAP-FEIA. Atopic eczema was found to be closely associated with IgE-FS in infants attending a dermatology department.
Publisher: Springer Science and Business Media LLC
Date: 12-1991
DOI: 10.1038/354384A0
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.ANAI.2015.06.001
Abstract: The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.
Publisher: Wiley
Date: 17-03-2004
Publisher: Informa UK Limited
Date: 17-11-2019
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.ANAI.2015.06.003
Abstract: Few studies exist on food sensitization and challenge-proven food allergy in low- and middle-income countries. To describe the study design and methodology to recruit infants from an African population for skin prick testing and oral food challenges and the use of preliminary data to investigate the extent to which the study s le is representative of the target population. Children 12 to 36 months old were recruited from childcare education facilities in Cape Town. Children underwent skin prick testing to foods. Those with a reactive wheal of at least 1 mm larger than the negative control and not clearly tolerant according to history to a full age-appropriate portion to at least 1 food underwent oral food challenges. Parents who chose not to participate completed a nonparticipant questionnaire. Interim analysis of at least 500 respondents was performed. Demographic features of participating children were compared with those of nonparticipants and the population demographics of the most recent Cape Town census data. The response rate was 60.1%, with high participation and completion rates of 96.5% and 97.5%, respectively. Demographics of the completed participant s le were similar to those of the Cape Town census. Use of a nonrespondent questionnaire indicated no selection bias in favor of increased participation of participants with allergy. No ethnic differences in sensitization or food allergy were evident. The study was safe and feasible and the recruitment was effective and representative of the target population. Future studies will aim to increase the precision of the prevalence of food sensitization and allergy, describe environmental risk factors, and include a rural black African cohort.
Publisher: Wiley
Date: 23-02-2010
DOI: 10.1111/J.1399-0004.2009.01308.X
Abstract: Hereditary hemochromatosis (HH), most often due to HFE C282Y homozygosity, is an iron overload disorder that can result in severe morbidity including hepatic cirrhosis. Predisposition to HH is easily diagnosed and morbidity is preventable by maintaining normal body iron and thus calls have been made to introduce community screening. The current study has been designed to assess the acceptability and feasibility of HH screening in high schools. Students (mostly 15-16 years of age) watched a purpose-designed DVD for education about HH. Those with parental consent were then offered cheek-brush screening for C282Y. Students completed a questionnaire prior to screening. The program was offered to 9187 students at 32 schools and 3489 (38%) had screening. Nineteen C282Y homozygotes (1 in 183) and 376 heterozygotes (1 in 9.3) were identified. More than 90% of students answered each of five knowledge questions correctly. Eight homozygotes (42%) had elevated transferrin saturation, but only two (10.5%) had marginally elevated serum ferritin (SF). We have shown that genetic screening for HH can successfully be offered in the high school setting. Ongoing research in this study will answer questions about the impact of high school students learning that they are at risk of HH.
Publisher: MDPI AG
Date: 15-10-2013
Publisher: BMJ
Date: 07-2015
Abstract: Implications for practice and research: Peanut or tree nut avoidance during pregnancy is not recommended for non-allergic mothers. Maternal nut consumption does not appear to increase the risk of nut allergy in offspring and may even be protective. Further research is required to clarify the role of maternal nut consumption during pregnancy and lactation research should consider potential differential effects of the genetic risk of peanut allergy in children.
Publisher: Wiley
Date: 03-2015
DOI: 10.1038/CTI.2015.2
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.JACI.2013.05.038
Abstract: Ninety-five percent positive predictive values (PPVs) provide an invaluable tool for clinicians to avoid unnecessary oral food challenges. However, 95% PPVs specific to infants, the age group most likely to present for diagnosis of food allergy, are limited. We sought to develop skin prick test (SPT) and allergen-specific IgE (sIgE) thresholds with 95% PPVs for challenge-confirmed food allergy in a large population-based cohort of 1-year-old infants with challenges undertaken irrespective of SPT wheal size or previous history of ingestion. HealthNuts is a population-based, longitudinal food allergy study with baseline recruitment of 1-year-old infants. Infants were recruited from council-run immunization sessions during which they underwent SPTs to 4 allergens: egg, peanut, sesame, and cow's milk/shrimp. Any infant with a detectable SPT response was invited to undergo oral food challenge and sIgE testing. Five thousand two hundred seventy-six infants participated in the study. Peanut SPT responses of 8 mm or greater (95% CI, 7-9 mm), egg SPT responses of 4 mm or greater (95% CI, 3-5 mm), and sesame SPT responses of 8 mm or greater (95% CI, 5-9 mm) had 95% PPVs for challenge-proved food allergy. Peanut sIgE levels of 34 kUA/L or greater (95% CI, 14-48 kUA/L) and egg sIgE levels of 1.7 kUA/L or greater (95% CI, 1-3 kUA/L) had 95% PPVs for challenge-proved food allergy. Results were robust when stratified on established risk factors for food allergy. Egg SPT responses and sIgE levels were poor predictors of allergy to egg in baked goods. These 95% PPVs, which were generated from a unique dataset, are valuable for the diagnosis of food allergy in young infants and were robust when stratified across a number of different risk factors.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JACI.2018.10.020
Abstract: This review highlights research and policy advances in food allergy that were published in 2017 in the Journal and beyond. In 2017, many important studies on the treatment of food allergy were published, bringing us ever closer to a standardized treatment for food allergy. Other important advancements included research into other management strategies, including thresholds for avoidance, management of food allergies in schools, and development of new guidelines for prevention of food allergy. There were several important epidemiologic studies helping us understand the phenotypes of allergic disease, and new hypotheses were proposed for how best to prevent food allergy. Finally, there was a welcome increased attention to non-IgE-mediated food allergies.
Publisher: Wiley
Date: 04-04-2017
DOI: 10.1111/ALL.13143
Abstract: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery s le) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these in iduals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent s le group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components. SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery s le (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
Publisher: Wiley
Date: 28-05-2013
DOI: 10.1111/CEA.12092
Abstract: 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. We aimed to measure the population prevalence of infantile eczema using novel s ling methodology, and identify socio-demographic risk factors for eczema in the first year of life. 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. 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. 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.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.JACI.2016.12.966
Abstract: Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.
Publisher: Springer Science and Business Media LLC
Date: 02-08-2015
DOI: 10.1007/S11882-015-0555-8
Abstract: Tree nuts are one of the most common foods causing acute allergic reactions and nearly all tree nuts have been associated with fatal allergic reactions. Despite their clinical importance, tree nut allergy epidemiology remains understudied and the prevalence of tree nut allergy in different regions of the world has not yet been well characterised. We aimed to systematically review the population prevalence of tree nut allergy in children and adults. We searched three electronic databases (OVID MEDLINE, EMBASE and PubMed) from January 1996 to December 2014. Eligible studies were categorised by age, region and method of assessment of tree nut allergy. Of the 36 studies identified most were in children (n = 24) and from Europe (n = 18), UK (n = 8) or USA (n = 5). Challenge-confirmed IgE-mediated tree nut allergy prevalence was less than 2 % (although only seven studies used this gold standard) while probable tree nut allergy prevalence ranged from 0.05 to 4.9 %. Prevalence estimates that included oral allergy syndrome (OAS) reactions to tree nut were significantly higher (8-11.4 %) and were predominantly from Europe. Prevalence of in idual tree nut allergies varied significantly by region with hazelnut the most common tree nut allergy in Europe, walnut and cashew in the USA and Brazil nut, almond and walnut most commonly reported in the UK. Monitoring time trends of tree nut allergy prevalence (both overall and by in idual nuts) as well as the prevalence of OAS should be considered given the context of the overall recent rise in IgE-mediated food allergy prevalence in the developed world.
Publisher: Wiley
Date: 02-06-2019
DOI: 10.1111/ALL.13822
Abstract: In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. In a birth cohort (n = 1074), the proportion of nTreg in the CD4 A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.
Publisher: Wiley
Date: 19-04-2011
DOI: 10.1111/J.1537-2995.2011.03141.X
Abstract: Questionnaire-based studies investigating blood donation history rely on the accurate recall of information from participants for results to be valid. This study aimed to retrieve electronic records from a national blood donation service and link them to self-reported history of donation to assess agreement between the two sources. Between 2004 and 2006, a s le of participants of northern European descent was selected from the Melbourne Collaborative Cohort Study (n = 31,192) to participate in the "HealthIron" study (n = 1438). A total of 1052 participants completed questionnaires that included questions about blood donation history. In 2009, consenting participants' records were linked to the Australian Red Cross Blood Service (ARCBS) to provide information on blood donations made between 1980 and follow-up (2004-2006). Those who commenced blood donation before 1980 were excluded. A total of 718 participants were available for analysis. Of these, 394 (55%) provided signed consent, including 182 (82%) of the 227 participants who self-reported ever donating blood. The two data sources were concordant for 331 (87%) of participants, with a κ statistic of 0.74 (SE, 0.05) indicating a high level of agreement. Participants tended to overstate by a factor of 2.0 (95% confidence interval, 1.7-2.2) the number of donations they had made when compared with ARCBS records. Participants in studies assessing self-reported blood donation history are likely to correctly indicate whether or not they have ever donated blood. Quantitative estimates are potentially inaccurate and could benefit from validating a s le of records to quantify the bias.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2011
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JACI.2017.02.019
Abstract: The HealthNuts study previously reported interim prevalence data showing the highest prevalence of challenge-confirmed food allergy in infants internationally. However, population-derived prevalence data on challenge-confirmed food allergy and other allergic diseases in preschool-aged children remain sparse. This study aimed to report the updated prevalence of food allergy at age 1 year from the whole cohort, and to report the prevalence of food allergy, asthma, eczema, and allergic rhinitis at age 4 years. HealthNuts is a population-based cohort study with baseline recruitment of 5276 one-year-old children who underwent skin prick test (SPT) to 4 food allergens and those with detectable SPT results had formal food challenges. At age 4 years, parents completed a questionnaire (81.3% completed) and those who previously attended the HealthNuts clinic at age 1 year or reported symptoms of a new food allergy were invited for an assessment that included SPT and oral food challenges. Data on asthma, eczema, and allergic rhinitis were captured by validated International Study of Asthma and Allergies in Childhood questionnaires. The prevalence of challenge-confirmed food allergy at age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI, 0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to 17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty percent to 50% of this population-based cohort experienced symptoms of an allergic disease in the first 4 years of their life. Although the prevalence of food allergy decreased between age 1 year and age 4 years in this population-based cohort, the prevalence of any allergic disease among 4-year-old children in Melbourne, Australia, is remarkably high.
Publisher: Elsevier BV
Date: 2014
Publisher: Wiley
Date: 29-07-2013
DOI: 10.1111/CEA.12090
Abstract: There have been dramatic changes in timing of first exposure to solid foods for children over the last 40 years, ranging from exposure prior to 4 months of age for most infants in the 1960s, to guidelines recommending delaying solids until after 6 months of age introduced in the 1990s. Infant diet, specifically age of weaning and age at introduction of allergenic foods, has long been thought to play a role food allergy. However, controversy surrounding the relationship between timing of introduction of foods and development of food allergy has lead to a plethora of inconsistent infant feeding guidelines both between and within countries. The aims of this article were to discuss the history of changing guidelines for optimal timing of introduction of solids in general and allergenic solids in particular and the evidence (or lack thereof) underpinning recommendations at each of these time-points. We present the current clinical equipoise with regards to recently revised guidelines published almost simultaneously in the UK, US and Australia and argue that guideline modification about timing of introduction (both for high risk infants but also for the general population) will require careful review of emerging literature to provide a true evidence base to inform public health practice such as infant feeding guidelines.
Publisher: Wiley
Date: 17-01-2019
DOI: 10.1111/ALL.13707
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.JACI.2013.11.032
Abstract: 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. We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort. The HealthNuts study is a prospective, population-based 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 challenge-confirmed 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. 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 = .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 = .009). Mutation in the filaggrin gene was not associated with the resolution of either egg allergy or egg sensitization at age 2 years. 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.
Publisher: Springer Science and Business Media LLC
Date: 20-06-2017
DOI: 10.1007/S11882-017-0718-X
Abstract: This article summarises recent developments on the prevention of food allergy in terms of the 5 D's of the development of food allergy: dry skin, diet, dogs, dribble, and vitamin D. While several advances have improved our understanding of the development of food allergy, few preventive strategies have been implemented beyond changes in infant feeding guidelines. These now state that the introduction of allergenic solids such as peanuts should occur in the first year of life. Results from randomised controlled trials on other allergenic solids, vitamin D supplementation, BCG immunisation at birth and eczema prevention are eagerly anticipated in order to inform further preventative strategies.
Publisher: Wiley
Date: 17-08-2011
Publisher: American Medical Association (AMA)
Date: 13-02-2006
DOI: 10.1001/ARCHINTE.166.3.294
Abstract: Hemochromatosis in white subjects is mostly due to homozygosity for the common C282Y substitution in HFE. Although clinical symptoms are preventable by early detection of the genetic predisposition and prophylactic treatment, population screening is not currently advocated because of the discrepancy between the common mutation prevalence and apparently lower frequency of clinical disease. This study compared screening for hemochromatosis in subjects with or without a family history. We assessed disease expression by clinical evaluation and liver biopsy in 672 essentially asymptomatic C282Y homozygous subjects identified by either family screening or health checks. We also observed a subgroup of untreated homozygotes with normal serum ferritin levels for up to 24 years. Prevalence of hepatic iron overload and fibrosis were comparable between the 2 groups. Disease-related conditions were more common in male subjects identified by health checks, but they were older. Hepatic iron overload (grades 2-4) was present in 56% and 34.5% of male and female subjects, respectively hepatic fibrosis (stages 2-4) in 18.4% and 5.4% and cirrhosis in 5.6% and 1.9%. Hepatic fibrosis and cirrhosis correlated significantly with the hepatic iron concentration, and except in cases of cirrhosis, there was a 7.5-fold reduction in the mean fibrosis score after phlebotomy. All subjects with cirrhosis were asymptomatic. Screening for hemochromatosis in apparently healthy subjects homozygous for the C282Y mutation with or without a family history reveals comparable levels of hepatic iron overload and disease. Significant hepatic fibrosis is frequently found in asymptomatic subjects with hemochromatosis and, except when cirrhosis is present, is reversed by iron removal.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.CLINBIOCHEM.2015.04.014
Abstract: In widely used protocols for the collection and isolation of cord blood mononuclear cells, investigators are left with substantial volumes of diluted plasma which could be used for other measurements. The aim of this study was to ascertain the validity of umbilical cord blood (UCB) diluted plasma s les for vitamin D, A and E analysis compared to UCB serum s les. Twenty UCB matched s les of diluted plasma and serum were collected. The s les were analysed by two liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods on two separate occasions. The results of 25(OH)D3 obtained by the two laboratories demonstrated close agreement with a mean difference of 0.14nmol/L [95% confidence interval (95% CI), -6.8 to 7.1]. Both methods demonstrate close agreement for 25(OH)D3 in UCB serum versus diluted UCB plasma mean difference 2.2nmol/L [95% CI, -9.5 to 13.9] and 4.1nmol/L [95% CI, -14.5 to 6.1] for the results from Lab A and Lab B, respectively. Vitamin A was quantified by Lab A in UCB serum and diluted UCB plasma mean difference 0.07μmol/L [95% CI, -0.41 to 0.28]. Results of 25(OH)D3 epimer and vitamin E in the diluted UCB plasma were below the limit of quantification, and could not be compared with UCB serum. Diluted UCB plasma can be used for the quantification of retinol and 25(OH)D3 by LC-MS/MS. By contrast, quantification of 25(OH)D3 epimer and vitamin E in diluted UCB plasma is not supported by this study due to limitations in analytical sensitivity.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JACI.2013.06.042
Abstract: There has been a dramatic proliferation of precautionary labeling by manufacturers to mitigate the perceived risk from low-level contamination from allergens in food. This has resulted in a significant reduction in choice of potentially safe foods for allergic consumers. We aimed to establish reference doses for 11 commonly allergenic foods to guide a rational approach by manufacturers based on all publically available valid oral food challenge data. Reference doses were developed from statistical dose-distribution modeling of in idual thresholds of patients in a dataset of more than 55 studies of clinical oral food challenges. Sufficient valid data were available for peanut, milk, egg, and hazelnut to allow assessment of the representativeness of the data used. The data were not significantly affected by the heterogeneity of the study methodology, including little effect of age on results for those foods for which sufficient numbers of adult challenge data were available (peanut and hazelnut). Thus by combining data from all studies, the eliciting dose for an allergic reaction in 1% of the population estimated for the following were 0.2 mg of protein for peanut, 0.1 mg for cow's milk, 0.03 mg for egg, and 0.1 mg for hazelnut. These reference doses will form the basis of the revised Voluntary Incidental Trace Allergen Labeling (VITAL) 2.0 thresholds now recommended in Australia. These new levels will enable manufacturers to apply credible precautionary labeling and provide increased consumer confidence in their validity and reliability, as well as improving consumer safety.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JAIP.2017.11.044
Abstract: We have previously developed a food allergy-specific developmental model, that explained emotions and coping styles, among children aged 6 to 15years in Ireland. The objective of this study was to investigate the usefulness of the developmental model in a large multicountry data set, including any mediators of coping style, and to use the findings to generate an item pool that will form the basis for 3 age-appropriate self-report questionnaires to measure coping and emotions. We conducted deductive thematic analysis on secondary data from interviews with 274 participants aged 6 to 23 years, and 119 parents from Australia, Ireland, Italy, the UK, and the USA. Analysis was undertaken across the entire data set. The Food Allergy Coping and Emotions (FACE) model has 5 major themes: (1) experiences and emotions, (2) search for normality, (3) management and coping, (4) "external mediators," and (5) "internal mediators" (between emotions and coping). These themes were present across countries, but differed according to age. Early-life experiences provide the foundation for later cognitions and behaviors. The expanded FACE developmental model is useful in explaining emotions and coping styles across different age groups and countries. These data will also be used to generate an age-specific bank of items for the development of 3 (age-specific self-report, and parent proxy) questionnaires to assess emotions and coping in food allergy. Findings provide insight into how particular styles of coping develop and vary from patient to patient and may also guide clinician-patient communication and the development of in idualized management strategies.
Publisher: American Academy of Pediatrics (AAP)
Date: 08-2017
Abstract: The National Academies of Sciences, Engineering, and Medicine convened an expert, ad hoc committee to examine critical issues related to food allergy. The authors of the resulting report, “Finding a Path to Safety in Food Allergy: Assessment of the Global Burden, Causes, Prevention, Management, and Public Policy,” evaluated the scientific evidence on the prevalence, diagnosis, prevention, and management of food allergy and made recommendations to bring about a safe environment for those affected. The committee recommended approaches to monitor prevalence, explore risk factors, improve diagnosis, and provide evidence-based health care. Regarding diagnostics, emphasis was placed on utilizing allergy tests judiciously in the context of the medical history because positive test results are not, in isolation, diagnostic. Evidence-based prevention strategies were advised (for ex le, a strategy to prevent peanut allergy through early dietary introduction). The report encourages improved education of stakeholders for recognizing and managing as well as preventing allergic reactions, including an emphasis on using intramuscular epinephrine promptly to treat anaphylaxis. The report recommends improved food allergen labeling and evaluation of the need for epinephrine autoinjectors with a dosage appropriate for infants. The committee recommended policies and guidelines to prevent and treat food allergic reactions in a various settings and suggested research priorities to address key questions about diagnostics, mechanisms, risk determinants, and management. Identifying safe and effective therapies is the ultimate goal. This article summarizes the key findings from the report and emphasizes recommendations for actions that are applicable to pediatricians and to the American Academy of Pediatrics.
Publisher: Wiley
Date: 19-07-2012
DOI: 10.1111/J.1365-2222.2011.03823.X
Abstract: Food allergy is a growing clinical and public health problem world-wide. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, but it is yet to be determined whether environmental factors might act in interaction with genetic risk. That is to say, are environmental factors more likely to affect those genetically at risk? Family history is a strong risk factor for the development of food allergy as it co-aggregates with other atopic diseases and as such genetic factors do play an important role in food allergy risk. However, significant interest has now turned to the role of epigenetic modifications of the genome as the major mediator of gene-environment interaction. The consideration of the role of epigenetics in food allergy is likely to provide an insight into aetiological and biological disease mechanisms. This paper discusses the current state of knowledge regarding genetic and environmental risk factors for food allergy, and considers the potential for furthering our understanding of food allergy aetiology by examining the role of epigenetic variation.
Publisher: Springer Science and Business Media LLC
Date: 29-03-2016
DOI: 10.1038/TP.2016.32
Abstract: Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 ( IGF2 ) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study ( n =576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=−2.23% 95% CI=−3.68 to −0.77%), and across all six of the in idual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher ( g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=−3.89% 95% CI=−6.06 to −1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=−3.70% 95% CI=−5.90 to −1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2 / H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed.
Publisher: American Chemical Society (ACS)
Date: 05-07-2013
DOI: 10.1021/JP404326D
Publisher: Elsevier BV
Date: 2009
Publisher: AMPCo
Date: 06-2015
DOI: 10.5694/MJA14.01511
Publisher: Wiley
Date: 10-12-2014
Publisher: American Physiological Society
Date: 2016
Abstract: We tested whether the T helper (Th) type 2 (Th2) cell agonist and allergenic ligand IL-33 was associated with eosinophilic esophagitis (EoE) development in a pediatric cohort and whether IL-33 protein could induce disease symptoms in mice. Biopsies from EoE patients or controls were used to measure IL-33 mRNA and protein expression. Increased expression of IL-33 mRNA was found in the esophageal mucosa in EoE. IL-33 protein was detected in cells negative for CD45, mast cells, and epithelial cell markers near blood vessels. Circulating levels of IL-33 were not increased. The time course for IL-33 gene expression was quantified in an established Aspergillus fumigatus allergen mouse model of EoE. Because IL-33 induction was transient in this model and chronicity of IL-33 expression has been demonstrated in humans, naive mice were treated with recombinant IL-33 for 1 wk and esophageal pathology was evaluated. IL-33 application produced changes consistent with phenotypically early EoE, including transmural eosinophilia, mucosal hyperproliferation, and upregulation of eosinophilic genes and chemokines. Th2 cytokines, including IL-13, along with innate lymphoid cell group 2, Th1/17, and M2 macrophage marker genes, were increased after IL-33 application. IL-33-induced eosinophilia was ablated in IL-13 null mice. In addition, IL-33 induced a profound inhibition of the regulatory T cell gene signature. We conclude that IL-33 gene expression is associated with pediatric EoE development and that application of recombinant protein in mice phenocopies the early clinical phase of the human disease in an IL-13-dependent manner. IL-33 inhibition of esophageal regulatory T cell function may induce loss of antigenic tolerance, thereby providing a mechanistic rationale for EoE development.
Publisher: Springer Science and Business Media LLC
Date: 28-12-2008
Publisher: Wiley
Date: 22-10-2013
DOI: 10.1111/J.1440-0960.2012.00950.X
Abstract: There is an increasing awareness of food allergies in the community. Dermatologists frequently see patients with atopic eczema, where parents are extremely concerned about the role of food allergy. Advice given to parents regarding the timing of introduction of solid foods has changed markedly over the past decade. Whereas previous advice advocated delaying the introduction of solid foods until the infant's gastrointestinal system had matured, recent studies suggest that the introduction of solids from around 4 to 6 months may actually prevent the development of allergies. Studies on maternal dietary restrictions during pregnancy and lactation have led researchers to believe that antigen avoidance does not play a significant role in the prevention of atopic disease. Breastfeeding exclusively for 4 to 6 months has multiple benefits for mother and child, however, it does not convincingly prevent food allergies or decrease atopic eczema. New evidence suggests that the use of hydrolysed formulas does not delay or prevent atopic eczema or food allergy. This article aims to highlight current evidence and provide an update for dermatologists on the role of food exposure in the development of atopic disease, namely atopic eczema.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2015
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JACI.2017.10.024
Abstract: Food allergy naturally resolves in a proportion of food-allergic children without intervention however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood. This study aimed to define the innate immune profiles associated with egg allergy at age 1 year, determine the phenotypic changes that occur with the development of natural tolerance in childhood, and explore the relationship between early life innate immune function and serum vitamin D. This study used longitudinally collected PBMC s les from a population-based cohort of challenge-confirmed egg-allergic infants with either persistent or transient egg allergy outcomes in childhood to phenotype and quantify the functional innate immune response associated with clinical phenotypes of egg allergy. We show that infants with persistent egg allergy exhibit a unique innate immune signature, characterized by increased numbers of circulating monocytes and dendritic cells that produce more inflammatory cytokines both at baseline and following endotoxin exposure when compared with infants with transient egg allergy. Follow-up analysis revealed that this unique innate immune signature continues into childhood in those with persistent egg allergy and that increased serum vitamin D levels correlate with changes in innate immune profiles observed in children who developed natural tolerance to egg. Early life innate immune dysfunction may represent a key immunological driver and predictor of persistent food allergy in childhood. Serum vitamin D may play an immune-modulatory role in the development of natural tolerance.
Publisher: Wiley
Date: 27-11-2013
DOI: 10.1111/CGE.12053
Abstract: Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) in iduals were informed of their genotype by letter. We studied whether these in iduals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild-type homozygous (CC) in iduals. We found 586 of 5757 (1 in 10) screened in iduals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY in iduals than CC in iduals were informed about HH and had testing for HH. In conclusion, we found that informing CY in iduals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY in iduals should be informed of their genetic status when identified by population screening.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.JACI.2012.01.056
Abstract: Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis. We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random s le of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay. By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds. Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC.
Publisher: American Thoracic Society
Date: 09-2018
Publisher: Wiley
Date: 04-01-2006
DOI: 10.1111/J.1399-0004.2005.00566.X
Abstract: Education is an essential component of a genetic screening program. Knowledge outcomes were measured after large-scale workplace education and screening for genetic susceptibility to hereditary hemochromatosis. The aim was to assess knowledge of concepts presented, impact of mode of delivery, and knowledge retention. Education in a group setting was delivered via oral or video presentation and knowledge assessed using self-administered questionnaires at baseline, 1 month, and 12 months. Over 60% of 11 679 participants correctly answered all questions at baseline, scoring higher with clinical concepts (disease etiology and treatment) than genetic concepts (penetrance and genetic heterogeneity). Revising the education program significantly increased correct responses for etiology (p < 0.002), whilst modifying the knowledge assessment tool significantly increased correct responses for etiology (p < 0.001) and gene penetrance (p < 0.001). For three of the four concepts assessed, use of video was as effective as oral presentation for knowledge outcomes. A significantly higher proportion of those at increased risk of disease (n = 44) responded correctly at 12 months than did controls (n = 82 p = 0.011 for etiology, p = 0.002 for treatment and p = 0.003 for penetrance). Hence, genetic screening can be successfully offered in a group workplace setting, with participants remembering clinical concepts better than genetic concepts up to 1 year later.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.IAC.2017.09.001
Abstract: This review summarizes the current state of play with regard to food allergy prevention. Food allergy prevention strategies focused on promoting timely introduction of allergenic foods (predominantly peanut) into the infant diet have recently been introduced in several countries. Additional prevention strategies currently under investigation include optimizing infant vitamin D levels, modulating the gut microbiota through use of probiotics, and preventing eczema to reduce the risk of food sensitization through a damaged skin barrier.
Publisher: Springer Berlin Heidelberg
Date: 2014
Publisher: Wiley
Date: 15-09-2009
DOI: 10.1111/J.1398-9995.2009.02172.X
Abstract: The relationship between infant feeding patterns and the later development of food allergies has been the focus of much debate and research over the last decade. National recommendations have been made by many countries on how to feed infants to reduce the risk of food allergy but due to the lack of firm evidence the recommendations differ widely. This review has been developed as part of EuroPrevall, a European multicentre research project funded by the European Union, to document the differing feeding recommendations made across Europe, to investigate the current evidence base for any allergy prevention feeding recommendations and to identify areas where further research is needed. This review will also provide information which, when combined with the infant feeding data collected as part of EuroPrevall, will give an indication of compliance to national feeding guidelines which can be utilised to assess the effectiveness of current dissemination and implementation strategies.
Publisher: Wiley
Date: 23-02-2017
DOI: 10.1111/ALL.13122
Abstract: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.
Publisher: Nova Science Publishers
Date: 2023
DOI: 10.52305/JUTX4763
Publisher: Elsevier BV
Date: 12-2017
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000371703
Abstract: Eosinophilic oesophagitis (EoE) is an antigen-driven pan-oesophagitis that is defined by the presence of at least 15 eosinophils per high power field on oesophageal histology in conjunction with upper gastrointestinal symptoms. EoE is closely associated with atopic disorders, in particular with food allergy, and as for other atopic diseases in childhood, there is a strong preponderance of male patients who have this disorder. The mechanisms leading to EoE have been characterised at the molecular level. Eotaxin-3, interleukin-5 and interleukin-13 are the key effector molecules in EoE pathogenesis. EoE presents with a erse range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infancy, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnosis may also be ascertained as an incidental finding in patients undergoing gastroscopy for other suspected conditions, including coeliac disease. EoE is different from gastro-oesophageal reflux disease and does not improve in response to proton pump inhibitors. Therefore, EoE needs to be distinguished from so-called PPI-responsive oesophageal eosinophilia. The long-term prognosis of EoE remains poorly defined, and complications mainly relate to subepithelial remodelling and fibrosis that may result in dysmotility, dysphagia and oesophageal strictures. The treatment of EoE involves elimination diets and topical swallowed aerosolised corticosteroids, while biological therapies targeting molecular mechanisms have so far been unsuccessful. In children, elemental diets have proved highly effective, but multiple food elimination diets are more sustainable in the long term. Further randomised, controlled trials on dietary or pharmacological interventions are needed to inform the optimal long-term management of EoE.
Publisher: Wiley
Date: 16-03-2015
DOI: 10.1111/JGH.12804
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JAIP.2015.10.010
Abstract: A rise in both prevalence and public awareness of food allergy in developed countries means that clinicians and researchers are frequently asked to explain reasons for the increase in food allergy, and families are eager to know whether they can take steps to prevent food allergy in their children. In this review, we outline leading theories on risk factors for early life food allergy. We summarize the leading hypotheses to explain the increase in food allergy as "the 5 Ds": dry skin, diet, dogs, dribble (shared microbial exposure), and vitamin D. We discuss currently available evidence for these theories and how these can be translated into clinical recommendations. With the exception of dietary intervention studies, evidence for each of these theories is observational, and we describe the implications of this for explaining risk to families. Current infant feeding recommendations are that infants should be introduced to solids around the age of 4 to 6 months irrespective of family history risk and that allergenic solids do not need to be avoided, either by infants at the time of solid food introduction or by mothers whilst pregnant or lactating. Additional potential strategies currently being explored include optimization of early life skin barrier function through a decrease in drying soaps and detergents and an increase in the use of nonallergenic moisturizers. The investigation of the role of microbiota and vitamin D is ongoing and cannot yet be translated into clinical recommendations.
Publisher: Wiley
Date: 02-11-2014
DOI: 10.1111/JPC.12757
Abstract: Eosinophilic oesophagitis (EoE) is a key differential for gastro-oesophageal reflux (GOR) in children. It can be difficult for clinicians to decide which patients need referral for the assessment of EoE, which can only be confirmed by histological analysis of endoscopic biopsies. Recent guidelines recommend that EoE can only be diagnosed following the exclusion of GOR through empiric treatment with proton pump inhibitors prior to endoscopy. Some aspects of history are strongly suggestive of EoE: red flags for referral include poor weight gain in the context of reflux symptoms, choking during eating or food impaction. Therapeutic options include dietary allergen elimination or swallowed aerosolised corticosteroids. Other novel therapies have failed to demonstrate benefit, but novel diagnostic biomarkers to enable non-invasive disease ascertainment and follow-up show some promise.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JAIP.2017.10.019
Abstract: The risk of developing asthma in those with early food allergy is unknown, particularly when early life food allergy has resolved. To understand whether challenge-proven food allergy in infancy increases the risk of asthma at age 4 years, using data from a population-based cohort. A total of 5,276 12-month-old infants were recruited using a population-based s ling frame. Infants underwent skin prick test to egg, peanut, and sesame and those with a detectable skin prick test result had oral food challenges. At age 4 years, food challenges were repeated to determine persistence or resolution of food allergy. The association between food allergy and doctor-diagnosed asthma was examined using binomial regression in 2,789 participants. Children with food allergy at age 1 year had an increased risk of asthma (1 food allergy: relative risk [RR], 1.69 95% CI, 1.29-2.21 2 or more food allergies: RR, 2.76 95% CI, 1.94-3.92). The risk of asthma was highest in children with food allergy and coexistent eczema in infancy (RR, 2.87 95% CI, 2.22-3.70). Transient food allergy and persistent food allergy were both associated with an increased risk of asthma (transient egg allergy: RR, 1.92 95% CI, 1.46-2.51 persistent egg allergy: RR, 2.60 95% CI, 1.76-3.85). Asthma at age 4 years is twice as common in those with challenge-proven food allergy at age 1 year, irrespective of whether the food allergy subsequently resolves. Children with 2 or more food allergies and those with coexistent eczema were almost 3 times as likely to develop asthma compared with those with no food allergies.
Publisher: MDPI AG
Date: 04-2016
DOI: 10.3390/IJMS17040485
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
Publisher: Wiley
Date: 14-09-2009
Publisher: Wiley
Date: 29-03-2016
DOI: 10.1111/CEA.12699
Abstract: Asian infants born in Australia are three times more likely to develop nut allergy than non-Asian infants, and rates of challenge-proven food allergy in infants have been found to be unexpectedly high in metropolitan Melbourne. To further investigate the risk factors for nut allergy, we assessed the whole-of-state prevalence distribution of parent-reported nut allergy in 5-year-old children entering school. Using the 2010 School Entrant Health Questionnaire administered to all 5-year-old children in Victoria, Australia, we assessed the prevalence of parent-reported nut allergy (tree nut and peanut) and whether this was altered by region of residence, socio-economic status, country of birth or history of migration. Prevalence was calculated as observed proportion with 95% confidence intervals (CI). Risk factors were evaluated using multivariable logistic regression and adjusted for appropriate confounders. Parent-reported nut allergy prevalence was 3.1% (95% CI 2.9-3.2) amongst a cohort of nearly 60 000 children. It was more common amongst children of mothers with higher education and socio-economic index and less prevalent amongst children in regional Victoria than in Melbourne. While children born in Australia to Asian-born mothers (aOR 2.67, 95% CI 2.28-3.27) were more likely to have nut allergy than non-Asian children, children born in Asia who subsequently migrated to Australia were at decreased risk of nut allergy (aOR 0.1, 95% CI 0.03-0.31). Migration from Asia after the early infant period appears protective for the development of nut allergy. Additionally, rural regions have lower rates of nut allergy than urban areas.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JAIP.2017.03.013
Abstract: Infant feeding in the first postnatal year of life has an important role in an infant's risk of developing food allergy. Consumer infant feeding advice is erse and lacks consistency. The Australian Infant Feeding Summit was held with the aim of achieving national consensus on the wording of guidelines for infant feeding and allergy prevention. Two meetings were hosted by the Centre for Food and Allergy Research, the Australasian Society of Clinical Immunology and Allergy, and the Australian National Allergy Strategy. The first meeting of 30 allergy researchers, clinicians, and consumers assessed the evidence. The second consensus meeting involved 46 expert stakeholders including state and federal health care agencies, consumers, and experts in allergy, infant feeding, and population health. Partner stakeholders agreed on consensus wording for infant feeding advice: CONCLUSIONS: Consensus was achieved in a context in which there is a high prevalence of food allergy. Guidelines for other countries are being updated. Provision of consistent wording related to infant feeding to reduce food allergy risk will ensure clear consumer advice.
Publisher: Wiley
Date: 25-01-2017
DOI: 10.1111/ALL.13114
Abstract: It has been hypothesized that n-3 PUFA in breast milk may assist immune and lung development. There are very limited data on possible long-term effects on allergic disease and lung function. The aim was to investigate associations of n-3 and n-6 PUFA levels in colostrum and breast milk with allergic disease and lung function at ages 12 and 18 years. Polyunsaturated fatty acids were measured in 194 colostrum s les and in 118 three-month expressed breast milk s les from mothers of children enrolled in the Melbourne Atopy Cohort (MACS) Study, a high-risk birth cohort study. Associations with allergic diseases, skin prick tests and lung function assessed at 12 and 18 years were estimated using multivariable regression. Higher levels of n-3 but not n-6 PUFAs in colostrum were associated with a trend towards increased odds of allergic diseases, with strong associations observed for allergic rhinitis at 12 (OR = 5.69[95% CI: 1.83,17.60] per weight%) and 18 years (4.43[1.46,13.39]) and eczema at 18 years (9.89[1.44, 68.49]). Higher levels of colostrum n-3 PUFAs were associated with reduced sensitization (3.37[1.18, 9.6]), mean FEV Higher levels of colostrum n-3 PUFAs were associated with increased risks of allergic rhinitis and eczema up to 18 years, and sensitization and reduced lung function at 12 years. As residual confounding may have caused these associations, they should be replicated, but these results could indicate that strategies that increase maternal n-3 PUFA intake may not aid in allergic disease prevention.
Publisher: Wiley
Date: 21-09-2012
DOI: 10.1111/J.1365-2222.2011.03868.X
Abstract: There is an emerging consensus that, as with other risks in society, zero risk for food-allergic people is not a realistic or attainable option. Food allergy challenge data and new risk assessment methods offer the opportunity to develop quantitative limits for unintended allergenic ingredients which can be used in risk-based approaches. However, a prerequisite to their application is defining a tolerable level of risk. This requires a value judgement and is ultimately a 'societal' decision that has to involve all relevant stakeholders. The aim of the workshop was to bring together key representatives from the stakeholders (regulators, food industry, clinical researchers and patients), and for the first time ever discuss the definition of a tolerable level of risk with regard to allergic reactions to food. The discussions revealed a consensus that zero risk was not a realistic option and that it is essential to address the current lack of agreed action levels for cross-contamination with allergens if food allergen management practice is to be improved. The discussions also indicated that it was difficult to define and quantify a tolerable level of risk, although both the clinical and the industry groups tried to do so. A consensus emerged that doing nothing was not a viable option, and there was a strong desire to take action to improve the current situation. Two concrete actions were suggested: (1) Action levels should be derived from the data currently available. Different scenarios should be examined and further developed in an iterative process. On the basis of this work, a tolerable level of risk should be proposed. (2) 'One-dose' clinical trial with a low challenge dose should be performed in multiple centres to provide additional information about the general applicability of dose-distribution models and help validate the threshold levels derived.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAIP.2018.08.038
Abstract: Overall early exposure to allergenic foods in the infant's diet is a new strategy for preventing food allergy to that allergen, but the optimal timing of exposure for different allergens is not known. We aimed to examine the relationship between exposure to cow's milk protein in the first 3 months of life and risk of cow's milk allergy at age 12 months. HealthNuts is a longitudinal population-based food allergy study that recruited 5,276 twelve-month-old infants. Skin prick testing to cow's milk was conducted on the second half of the cohort (n = 2,715) and sensitization defined as a wheal ≥2 mm. Cow's milk allergy was defined as a parent-reported reaction to cow's milk consistent with IgE-mediated allergy together with evidence of sensitization. Early exposure to cow's milk protein was captured through parental questionnaire administered at 1 year of age and defined as consumption of cow's milk-based infant formula during the first 3 months of life. Forty-two percent of infants were exposed to cow's milk in the first 3 months of life (n= 1,977/4,712) and 87% of these infants were also breastfed. Early exposure to cow's milk protein was associated with a reduced risk of cow's milk sensitization (adjusted odds ratio [aOR] 0.44, 95% confidence interval [CI] 0.23-0.83), parent-reported reactions to cow's milk (aOR 0.44, 95% CI 0.29-0.67), and cow's milk allergy (aOR 0.31, 95% CI 0.10-0.91) at age 12 months. Age at exposure to cow's milk protein was not associated with the risk of other food allergies. Exposure to cow's milk protein in the first 3 months of life was associated with a reduced risk of cow's milk allergy. These findings are from an observational study and clinical trials are warranted to further assess this association before any recommendations to infant feeding guidelines can be made.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.BBRC.2012.08.134
Abstract: Methylmalonic aciduria is a rare disorder caused by an inborn error of organic acid metabolism. Current treatment options are limited and generally focus on disease management. We aimed to investigate the use of fetal progenitor cells to treat this disorder using a mouse model with an intermediate form of methylmalonic aciduria. Fetal liver cells were isolated from healthy fetuses at embryonic day 15-17 and intravenously transplanted into sub-lethally irradiated mice. Liver donor cell engraftment was determined by PCR. Disease correction was monitored by urine and blood methylmalonic acid concentration and weight change. Initial studies indicated that pre-transplantation sub-lethal irradiation followed by transplantation with 5 million cells were suitable. We found that a double dose of 5 million cells (1 week apart) provided a more effective treatment. Donor cell liver engraftment of up to 5% was measured. Disease correction, as defined by a decrease in blood methylmalonic acid concentration, was effected in methylmalonic acid mice transplanted with a double dose of cells and who showed donor cell liver engraftment. Mean plasma methylmalonic acid concentration decreased from 810 ± 156 (sham transplanted) to 338 ± 157 μmol/L (double dose of 5 million cells) while mean blood C3 carnitine concentration decreased from 20.5 ± 4 (sham transplanted) to 5.3 ± 1.9 μmol/L (double dose of 5 million cells). In conclusion, higher levels of engraftment may be required for greater disease correction however these studies show promising results for cell transplantation biochemical correction of a metabolic disorder.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.ANAI.2017.11.023
Abstract: Allergic diseases have increased dramatically in the developed world during the past few decades, yet the understanding of risk factors and effective prevention approaches remain limited. In this review, we summarize the evidence supporting the hypothesis that skin-barrier impairment and early-life atopic dermatitis (AD) could play a causal role in the development of sensitization and subsequent food allergies and allergic airways disease (allergic asthma and rhinitis). We further discuss the potential to target the skin barrier as a means to lower the incidence of allergic disease. Review of published literature. Narrative. There is a strong link between AD and sensitization, food allergy, asthma, and allergic rhinitis, particularly AD that is severe and commences in the first 6 months of life. There also is emerging evidence that regular use of prophylactic emollients can significantly decrease the expression of AD, at least while treatment continues. Studies are exploring whether decreased AD expression might modulate the allergic response at a more fundamental level and potentially alter the association between early-life AD and subsequent development of food allergy and allergic airways disease. Although at this point there is only indirect evidence that early-life emollient use might prevent AD and food allergy, early studies are encouraging. The results of high-quality prevention trials that are in progress are eagerly anticipated. If found to be effective, then neonatal emollient use could be a simple public health measure to lower the incidence of AD, food allergies, and allergic airways disease in future generations.
Publisher: Wiley
Date: 12-11-2015
DOI: 10.1111/JPC.12760
Abstract: To report the cumulative incidence, health-seeking behaviour and medical intervention of infants with gastro-oesophageal reflux (GOR) in the first year of life. The HealthNuts study is a longitudinal, population-based study. At 12 months of age, infants underwent skin prick testing to food allergens, including cows milk. Parents completed a questionnaire on GOR symptoms, food allergy and treatments. Factors associated with seeking health care for infants with GOR were modelled using logistic regression. Of 4674 infants, parents reported GOR in 1054 (23% 95% confidence interval (CI) 21.4-23.8). Parents consulted a medical practitioner in 662 (64%) cases. Symptoms commenced in the first month in 411 (48%) and resolved within 6 months in 703 (75%) infants. Factors associated with doctor consultation for GOR were prematurity (adjusted odds ratio (aOR) 1.94 95% CI 1.43-2.63) and family history of atopy (aOR 1.64 95% CI 1.1-2.43). Eight per cent of infants (371/4674 95% CI 7.2-8.7) received anti-reflux medication and 6% (296/4674 95% CI 5.7-7.1) changed formula. Parents were more likely to seek treatment if they perceived their infant to be unsettled (aOR 2.55 95% CI 1.26-5.17) and if the duration of GOR was prolonged (aOR 3.36 for symptoms >6 months 95% CI 1.83-6.17). In the first year of life, approximately 14% of the population seek medical advice for GOR symptoms. The use of anti-reflux medication in the general community remains high, despite the absence of evidence that it is appropriate or effective for uncomplicated GOR.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.JACI.2016.04.011
Abstract: A recent randomized trial (the Learning Early About Peanut Allergy [LEAP] study) provided evidence that earlier dietary peanut introduction reduces peanut allergy prevalence in high-risk infants. However, questions remain as to how to identify and target the "at-risk" population to facilitate timely introduction of peanut. We sought to use population-based infant peanut allergy data to understand feasibility and implications of implementing the LEAP trial intervention. Using the HealthNuts study cohort (n = 5276) of 1-year-old infants, we explored the impact of using various criteria to identify infants at high risk of developing peanut allergy, and the implications of skin prick test (SPT) screening before peanut introduction. Screening all infants with early onset eczema and/or egg allergy could require testing 16% of the population and would still miss 23% of peanut allergy cases 29% of screened infants would require clinical follow-up because of being SPT-positive. Around 11% of high-risk infants were excluded from the LEAP study because of an SPT wheal size of more than 4 mm to peanut at baseline data from the HealthNuts study suggest that 80% of these would be peanut allergic on food challenge. There were no life-threatening events among either low- or high-risk infants whose parents chose to introduce peanut at home in the first year of life, or in 150 peanut-allergic infants during hospital-based challenges. Based on this large epidemiological study, a population program aiming to identify and screen all infants at risk of peanut allergy would pose major cost and logistic challenges that need to be carefully considered. Further research might be required to provide data for low-risk infants.
Publisher: Oxford University Press (OUP)
Date: 07-04-2017
DOI: 10.1093/IJE/DYW042
Abstract: The maternal and infant microbiome may influence infant cardiovascular risk through immune programming. The maternal vagino-enteric microbiome is often s led for group B streptococcus (GBS) colonization during pregnancy. Our aim was to investigate the association between maternal GBS colonization, intrapartum antibiotics, antenatal pet exposure and infant aortic intima-media thickness (aIMT), an intermediate vascular phenotype, and whether this association varied by mode of delivery. The Barwon Infant Study is a population-derived pre-birth cohort. Perinatal data were collected on participants. Women were tested for vagino-enteric group B streptococcus (GBS) colonization during third trimester. Six-week infant aIMT was measured by trans-abdominal ultrasound. Adjustment for confounders included maternal age, pre-pregnancy body mass index (BMI), smoking, socioeconomic status, gestational diabetes, length of gestation, infant sex, birthweight and aortic internal diameter. Data were available on 835 mother-infant pairs. Of these, 574 (69%) women delivered vaginally of those, 129 (22%) were GBS-colonized and of these women, 111 (86%) received prophylactic intrapartum antibiotics. An association between maternal GBS colonization and infant aIMT was observed among those delivered vaginally (β = 19.5 µm, 95% CI 9.5, 29.4 P < 0.0001) but not by Caesarean section ( P for interaction = 0.02). A similar pattern was seen for intrapartum antibiotics. There was a negative association between antenatal pet exposure and aIMT observed in those delivered vaginally. Maternal GBS colonization and intrapartum antibiotics were associated with increased infant aIMT in those delivered vaginally, whereas antenatal pet exposure was associated with decreased aIMT. These data suggest that differences in early life microbial experience may contribute to an increased cardiovascular risk.
Publisher: Wiley
Date: 04-11-2015
DOI: 10.1111/APA.13151
Abstract: To synthesise the evidence on the association between duration and exclusivity of breastfeeding and the risk of acute otitis media (AOM). Systematic review and meta-analysis following searching of PubMed, CINAHL and EMBASE electronic databases. Twenty-four studies, all from the USA or Europe, met the inclusion criteria. In the pooled analyses, any form of breastfeeding was found to be protective for AOM in the first 2 years of life. Exclusive breastfeeding for the first 6 months was associated with the greatest protection (OR 0.57 95% CI 0.44, 0.75), followed by 'more vs less' breastfeeding (OR 0.67 0.59, 0.76) and 'ever vs never' breastfeeding (OR 0.67 0.56, 0.80). This systematic review and meta-analysis provides evidence that breastfeeding protects against AOM until 2 years of age, but protection is greater for exclusive breastfeeding and breastfeeding of longer duration. Exclusive breastfeeding during the first 6 months was associated with around a 43% reduction in ever having AOM in the first 2 years of life. After 2 years of age, there is no evidence that breastfeeding protects against AOM however, there were few studies and the evidence quality was low.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JPEDS.2016.08.064
Abstract: To evaluate the associations between breastfeeding duration, age at solids introduction, and their interaction in relation to infant (age 9-15 months) above normal body mass index (BMI). Cross-sectional, population-based study with 3153 infants from Melbourne (2007-2011). Above normal BMI (z score > 2, equivalent to >97.7th percentile) defined using the World Health Organization standard. Both longer duration of full and any (full or partial) breastfeeding were associated with lower odds of above normal BMI (eg, aOR, 0.37 [95% CI, 0.22-0.60] for full breastfeeding 4-5 months versus 0-1 months). Compared with introduction of solids at 5-6 months, both early and delayed introduction were associated with increased odds of above normal BMI (aOR for 4 months, 1.75 [95% CI, 1.10-2.80] and for ≥7 months, 2.64 [95% CI, 1.26-5.54] versus 6 months). Such associations differ by breastfeeding status at 4 months (interaction P = .08). Early introduction of solids was associated with increased odds of above normal BMI in both infants fully or partially breastfed for ≥4 months (aOR, 3.66 95% CI, 1.41-9.51) and those breastfed for <4 months (aOR, 3.11 95% CI, 1.39-6.97). Introduction of solids at ≥7 months was associated with increased odds of above normal BMI (aOR, 5.79 95% CI, 1.91-17.49) among infants breastfed for <4 months only. Introduction of solids at 5-6 months, compared with either early or delayed introduction, is associated with decreased odds of above normal BMI at 1 year of age, regardless of infants' breastfeeding status at 4 months. These results may have implications for public health guidelines with regard to recommendations about the optimal timing of the introduction of solid foods in infancy.
Publisher: Wiley
Date: 26-11-2012
DOI: 10.1111/J.1365-2222.2012.04061.X
Abstract: It is controversial whether egg-allergic children should strictly avoid all forms of egg, or if regular ingestion of baked egg will either delay or hasten the resolution of egg allergy. This is the first study to examine the relationship between frequency of baked egg ingestion and rate of decline in egg skin prick test size in egg-allergic children. This was a retrospective clinical cohort study. All children with challenge-proven egg allergy who attended the Royal Children's Hospital Allergy Department 1996-2005 and had at least two egg skin prick tests performed in this period were included (n = 125). Frequency of baked egg ingestion was assessed by telephone questionnaire as follows: (a) frequent (> once per week), (b) regular (> once every 3 months, up to ≤ once per week) or (c) strict avoidance (≤ once every 3 months). The relationship between frequency of baked egg ingestion and rate of decline in egg skin prick test size was examined by multiple linear regression, adjusting for potential confounders. Mean rate of decline in egg skin prick test size in all children was 0.7 mm/year (95% CI 0.5-1.0 mm/year). There was no evidence (P = 0.57) that the rate of decline in egg skin prick test size differed between children who undertook frequent ingestion (n = 21, mean 0.4 mm/year, 95% CI -0.3-1.2 mm/year), regular ingestion (n = 37, mean 0.9 mm/year, 95% CI 0.4-1.4 mm/year) or strict avoidance (n = 67, mean 0.7 mm/year, 95% CI 0.4-1.1 mm/year) of baked egg. Compared with strict dietary avoidance, frequent consumption of baked egg was not associated with a different rate of decline in egg skin prick test size in egg-allergic children. Given that dietary restrictions can adversely impact on the family, it is reasonable to consider liberalizing baked egg in the diet of egg-allergic children.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1038/GIM.2017.121
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 03-2017
Publisher: Springer Science and Business Media LLC
Date: 11-01-2012
Publisher: Wiley
Date: 27-07-2017
DOI: 10.1111/JPC.13616
Abstract: The aim of this study was to describe antibiotic exposure in Australian infants during the first year of life, focusing on antibiotic class, indication, risk factors associated with exposure and comparison with international counterparts. The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal s ling frame from a large regional centre in Victoria, Australia. Longitudinal data on infection and medication were collected at 1, 3, 6, 9 and 12 months by parental questionnaire and from general practitioner and hospital records. Predictors of questionnaire non-completion were identified. A total of 660 infants with complete serial data were comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic prescriptions and (ii) antibiotic days-exposed per person-year. Mean antibiotic prescription rate was 0.92 prescriptions (95% confidence interval (CI), 0.83-1.02) per person-year, with the highest rates in those aged <1 month (1.50 (95% CI, 1.09-1.91) per person-year). A total of 50.0% of infants were exposed to at least one antibiotic in their first year of life. Increasing number of siblings was associated with increased antibiotic exposure. Penicillin with extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics were prescribed for respiratory tract infections and bronchiolitis. Australian infants in this large population-based study are exposed to considerably more antibiotics than the majority of their international counterparts. Interventions aimed at addressing avoidable prescribing by medical practitioners and modifiable risk factors associated with antibiotic exposure may reduce antibiotic use.
Publisher: Wiley
Date: 23-12-2016
DOI: 10.1111/CEA.12685
Abstract: The LEAP randomized controlled trial provides the first direct evidence that delayed introduction of peanut in an infant's diet significantly increases the risk of peanut allergy. However, as often is the case in ground-breaking research, the LEAP study raises almost as many questions as it resolves. Although the quality of design and excellence in study execution is unquestioned, the particular difficulty this study raises is how to generalize results from a trial of high-risk infants, which screened infants for the presence of peanut allergy prior to peanut introduction, to the general population. Although many existing infant feeding guidelines already allow for the introduction of allergenic foods from 4 to 6 months of age irrespective of co-existent risk factors for peanut allergy, these will now need to be revised to more strongly state that avoidance may be harmful. Interim guidelines have already been published which incorporate these recommendations. However, the question as to how to achieve timely introduction of peanut into an infant's diet in a safe and cost-effective way, particularly in high-risk infants, remains unresolved.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.SEMARTHRIT.2011.11.003
Abstract: The evidence for an association between mutations in the HFE (hemochromatosis) gene and the risk of hip or knee osteoarthritis is inconsistent. Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. We examined the relationship between HFE gene mutations and risk of total hip and knee replacement using a prospective cohort study. The Melbourne Collaborative Cohort Study recruited participants between 1990 and 1994. Participants born in Australia, New Zealand, the United Kingdom, or Ireland (n = 27,848) were genotyped for the HFE C282Y mutation. Total hip and knee replacements for osteoarthritis during 2001 to 2009 were ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Hazard ratios (HR)/odds ratios (OR) and confidence intervals (CI) were obtained from Cox regression or logistic regression. Compared with those with no C282Y mutation, C282Y homozygotes had an increased risk of single total hip replacement (HR 1.94, 95% CI 1.04-3.62) and bilateral total hip replacement (OR 5.86, 95% CI 2.36-14.57) for osteoarthritis, adjusting for age, sex, body mass index, and educational level. Only 3 C282Y homozygotes had single total knee replacement the HR was 0.51 (95% CI 0.16-1.57). C282Y/H63D compound heterozygosity was not related to the risk of total hip or knee replacement. HFE C282Y homozygosity was associated with an increased risk of both single and bilateral total hip replacement for osteoarthritis.
Publisher: Portland Press Ltd.
Date: 04-02-2016
DOI: 10.1042/CS20150685
Abstract: Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother–infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9 μm/kg, 95%CI 11.1, 28.6 P& .001) and birth skinfold thickness (β=6.9 μm/mm, 95%CI 3.3, 10.5 P& .001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (β=11.3 μm/kg increase, 95%CI 2.2, 20.3 P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.
Publisher: Wiley
Date: 07-09-2012
DOI: 10.1111/ALL.12015
Abstract: Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between environmental and demographic factors and egg allergy in a population-based infant cohort. In a study of 5276 infants (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12 months of age. Questionnaire data on relevant exposures were obtained. 699/873 (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended for formal assessment of egg allergy status 453 had confirmed egg allergy (positive challenge and SPT ≥ 2 mm). Associations between environmental and demographic factors and egg allergy were investigated using multivariable logistic regression. Children with older siblings and those with a pet dog at home were less likely to develop egg allergy by 1 year of age (adjusted OR [aOR], 0.72 95% CI, 0.62, 0.83 per sibling and aOR, 0.72 95% CI, 0.52, 0.99, respectively). Caesarean section delivery, antibiotic use in infancy, childcare attendance and maternal age were not associated with egg allergy. History of allergic disease in an immediate family member and having parents born in East Asia were strong risk factors for infantile egg allergy (aOR, 1.82 95% CI, 1.40, 2.36 and aOR, 3.30 95% CI, 2.45, 4.45, respectively). Exposure in the first year of life to siblings and dogs may decrease the risk of subsequent egg allergy. Infants with a family history of allergy and those with parents born in East Asia are at increased risk of egg allergy.
Publisher: Wiley
Date: 22-12-2010
Publisher: Wiley
Date: 08-07-2016
DOI: 10.1111/ALL.12933
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JACI.2014.11.012
Abstract: Rapid environmental transition and modern lifestyles are likely driving changes in the bio ersity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These erse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For ex le, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.JAIP.2016.07.019
Abstract: Results from the Learning Early About Peanut trial and its follow-up study suggest that early peanut introduction in the diets of high-risk infants may prevent the development of peanut allergy. Allergy organizations around the world released a unified statement, the Consensus Communication on Early Peanut Introduction and the Prevention of Peanut Allergy in High Risk Infants, in response to results from the Learning Early About Peanut trial, which recommends early introduction of peanut into the diet of those children at greatest risk of development of peanut allergy. As a result, it is expected that practicing allergists will experience an increased demand to perform an oral food challenge (OFC) in infants. Allergists often perform OFCs however, conducting an OFC in an infant creates unique circumstances that have not been considered in previously published OFC guideline documents. The purpose of this workgroup report is to provide guidance to practitioners regarding the proper approach for conducting a peanut challenge in an infant.
Publisher: No publisher found
Date: 2011
Publisher: Elsevier BV
Date: 07-2005
Publisher: Wiley
Date: 26-11-2016
DOI: 10.1111/JPC.13026
Publisher: Oxford University Press (OUP)
Date: 20-04-2016
DOI: 10.1093/IJE/DYW011
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.JACI.2008.03.017
Abstract: 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2006
Publisher: Wiley
Date: 13-03-2011
Publisher: Informa UK Limited
Date: 24-09-2017
DOI: 10.3109/02770903.2014.936447
Abstract: Little is known about asthma readmissions within 28 days over time by age or gender. We explored trends in childhood asthma hospital readmission rates over time by age, gender and season. Using a large database of 53,156 childhood admissions with a primary diagnosis of asthma from the Department of Health Victoria Australia for 1997-2009, we explored asthma hospital readmissions rates by seasonality, gender and age (2-18 years) using chi square tests, logistic regression models and graphical techniques. Approximately 9459 (28%) of the children had two or more admissions over the whole study period, contributing to 55% (29,056/53,156) of all admissions. Approximately 5% of admissions were repeat admission within 28 days. Over time, despite a decline in asthma incidence, the rate of readmission within 28 days increased, particularly in the 2-12 year age groups. Girls were at greater risk of readmission within 28 days (odds ratio [OR] = 1.15 95% CI: 1.004-1.32 p = 0.04) and 12 months (OR = 1.11 95% CI: 1.05-1.19 p = 0.001). Grass pollen season was associated with readmissions within 28 days, but only in boys (p = 0.01). Over time, despite a fall in asthma incidence, readmission rates for childhood asthma significantly increased in younger age groups with girls at a higher risk of being readmitted than boys. Increased risk of repeat admission for boys was observed during the grass pollen season. These findings highlight high-risk groups, which has implications for both clinical services and patient care. More detailed monitoring of readmission rates amongst various risk groups over time is required.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.ENVRES.2017.05.026
Abstract: Elevated cord blood IgE is important on the pathway to allergic disease. The association between season of birth and infant cord blood IgE is not well-established. Study findings differ on which birth season is associated with higher cord blood IgE risk and its magnitude. We conducted a systematic review and meta-analysis of studies on season of birth and cord blood IgE. We searched Medline, Web of Science, Scopus and ProQuest Health databases, and reviewed reference lists of articles that met the inclusion criteria. All included studies measured IgE as a binary variable using various cut-off values. We performed multivariate-random-effects meta-analysis to handle an exposure with multiple categories of Season of Birth. Our search identified 275 records and 10 had sufficient data to be included in a meta-analysis. Relative to summer, winter birth had the greatest odds of high IgE (≥ 0.1IU/ml), meta-analysis OR = 1.24 (95%CI: 1.01-1.52). A similar OR, was found for IgE ≥ 0.5 IU/ml, OR = 1.30 (95%CI: 0.99-1.71). A winter season of birth was associated with statistically significant higher odds of elevated cord blood IgE at cut-off ≥ 0.1IU/ml but borderline at cut-off ≥ 0.5IU/ml. This winter effect is likely to be a marker for a range of other environmental exposures during specific stages of pregnancy, such as aeroallergen exposures, maternal infections and vitamin D levels. Further research is required to support our finding and to identify the exact mechanisms that lead to the winter season of birth effect on circulating IgE levels, as this may have implications for allergic disease prevention.
Publisher: Wiley
Date: 15-02-2008
DOI: 10.1111/J.1478-3231.2008.01661.X
Abstract: If community screening for hereditary haemochromatosis is to be considered, compliance with preventative measures and absence of significant psychological morbidity must be demonstrated. Workplace screening for the HFE C282Y mutation and then clinical care for C282Y homozygotes was instituted. Data were collected on understanding of test results, perceived health status and anxiety for C282Y homozygotes compared with controls. Uptake of clinical care, compliance and response to treatment and changes in diet were monitored for up to 4 years for C282Y homozygotes. After 11 307 in iduals were screened, 40/47 (85%) newly identified C282Y homozygotes completed questionnaires 12 months after diagnosis compared with 79/126 (63%) of controls. Significantly more C282Y homozygotes correctly remembered their test result compared with controls (95 vs 51%, P<0.0001). No significant difference in perceived health status was observed within or between the two groups at 12 months compared with baseline. Anxiety levels decreased significantly for C282Y homozygotes at 12 months compared with before testing (P<0.05). Forty-five of the 47 (95.8%) C282Y homozygotes accessed clinical care for at least 12 months. All 22 participants requiring therapeutic venesection complied with treatment for at least 12 months (range 12-47 months). In iduals at a high genetic risk of developing haemochromatosis use clinical services appropriately, maintain their health and are not 'worried well'. Population genetic screening for haemochromatosis can be conducted in the work place in a way that is acceptable and beneficial to participants.
Publisher: Wiley
Date: 29-09-2017
DOI: 10.1111/PAI.12764
Publisher: Elsevier BV
Date: 05-2018
Publisher: Wiley
Date: 07-09-2019
DOI: 10.1111/CEA.13251
Abstract: Asthma and allergic diseases are heterogeneous. Measurement of biomarkers in exhaled breath condensate (EBC) may help to discriminate between different phenotypes and may assist with clinical prognostication. We aimed to assess associations between total nitric oxide products (NO Cross-sectional analyses were nested within two Australian longitudinal studies, the Melbourne Atopy Cohort Study (MACS, mean age 17.8 years) and the Tasmanian Longitudinal Health Study (TAHS, mean age 49.4 years). Levels of EBC NO Atopy, with or without asthma or rhinitis, was associated with increased EBC NO In these population-based s les, EBC NO
Publisher: Wiley
Date: 19-11-2019
DOI: 10.1111/ALL.13572
Abstract: IgE-mediated egg allergy presents as one of the most common food allergies in children. Measurement of egg white specific IgE (sIgE) levels in serum or skin prick test has been shown to be a poor predictor of clinical allergy to raw egg white, and also to baked or cooked egg. Recent developments in component resolved diagnostic (CRD) technology have enabled us to improve the way in which we diagnose and predict peanut allergy by examining IgE specificity to in idual peptides. We aimed to investigate whether egg CRD could improve current methods to diagnose various egg allergy phenotypes as well as predict the development of tolerance to egg. Using the HealthNuts cohort of food challenge-proven egg allergic and egg-sensitized and egg-tolerant, age-matched 12-month infants with longitudinal follow-up at 2 and 4 years (n = 451), we measured serum egg white, Gal d 1, 2, 3 and 5 sIgE using ImmunoCAP. Gal d 1 sensitization increased the risk of persistent egg allergy by 2.5-fold. The production of sIgE to all four egg allergens (Gal d 1, 2, 3 or 5) increased the risk of having persistent raw egg allergy fourfold (OR 4.19 (95% CI: 1.25-14.07). We did not find any improvements of using Gal d 1, 2, 3 or 5 to diagnose current egg allergy compared to egg white sIgE. Sensitization to multiple egg allergens Gal d 1, 2, 3 or 5 may be a prognostic marker that could be useful for patient management and identifying in iduals at risk of developing persistent egg allergy.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.JACI.2015.06.001
Abstract: The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.
Publisher: Wiley
Date: 11-2000
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.YGYNO.2009.08.004
Abstract: Advanced gynecological surgery undertaken in a specialized gynecologic oncology unit may be associated with significant perioperative morbidity. Validated risk prediction models are available for general surgical specialties but currently not for gynecological cancer surgery. The objective of this study was to evaluate risk factors for adverse events (AEs) of patients treated for suspected or proven gynecological cancer and to develop a clinical risk score (RS) to predict such AEs. AEs were prospectively recorded and matched with demographical, clinical and histopathological data on 369 patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center. Stepwise multiple logistic regression was used to determine the best predictors of AEs. For the risk score (RS), the coefficients from the model were scaled using a factor of 2 and rounded to the nearest integer to derive the risk points. Sum of all the risk points form the RS. Ninety-five patients (25.8%) had at least one AE. Twenty-nine (7.9%) and 77 (20.9%) patients experienced intra- and postoperative AEs respectively with 11 patients (3.0%) experiencing both. The independent predictors for any AE were complexity of the surgical procedure, elevated SGOT (serum glutamic oxaloacetic transaminase, > or /=35 U/L), higher ASA scores and overweight. The risk score can vary from 0 to 14. The risk for developing any AE is described by the formula 100 / (1 + e((3.697 - (RS /2)))). RS allows for quantification of the risk for AEs. Risk factors are generally not modifiable with the possible exception of obesity.
Publisher: Wiley
Date: 29-09-2014
DOI: 10.1111/ALL.12487
Abstract: 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 not those with parent/s born in the UK/Europe (OR 0.8, 95% CI 0.4-1.5). Paradoxically rates of allergic disease were lower among Asian parents. A higher prevalence of eczema among infants of Asian parents explained around 30% of the increase in peanut allergy, while differences in dog ownership explained around 18%. The high peanut allergy prevalence among infants of Asian-born parents appears to have occurred in a single generation and was not present among infants with parents migrating from other countries, suggesting gene-environment interactions are important. The role of eczema and microbial exposure in food allergy prevention warrants exploration.
Publisher: Informa UK Limited
Date: 12-2013
Publisher: BMJ
Date: 31-10-2019
Publisher: Wiley
Date: 14-06-2011
Publisher: BMJ
Date: 15-09-2010
DOI: 10.1136/BMJ.C4616
Publisher: Wiley
Date: 07-03-2017
DOI: 10.1111/AJD.12621
Abstract: The newly revised Australian Infant Feeding Guidelines recommends that all infants, including those at high risk of allergy, be introduced foods traditionally considered allergenic (such as peanut butter, dairy, wheat and egg) within the first year of life. High-risk infants are those with early onset eczema (<3-months old) or with moderate to severe eczema not responding to treatment (<6-months old). Eczema can also represent a symptom of allergy presentation and the recommended introduction of some foods in this group may lead to allergic reactions at home. Although there have been no reported deaths from gradual food introduction to infants at home and cohort studies have only reported mild to moderate reactions, there is anecdotal evidence that more severe reactions can occur rarely. Allergic reactions, even if they are not life-threatening, can be a terrifying experience for parents. Dermatologists play an important role when dealing with high-risk infants in promoting the message of early allergenic food introduction yet also instigating appropriate allergy testing when necessary. This short review aims to provide an update to Australasian dermatologists on the newly revised Australian Infant Feeding Guidelines and provide a food allergy screening pathway for high-risk infants prior to commencement of allergenic foods.
Publisher: Mary Ann Liebert Inc
Date: 06-2004
Abstract: The objective of this study was to consider the objective evidence and ethical arguments for the appropriate age to test children at risk of developing hereditary hemochromatosis. A literature search for information on iron overload in children, onset of disease expression for hemochromatosis, and recommendations for age of cascade screening was undertaken. We examined the objective evidence and arguments for testing in early childhood and those for delaying testing until later teenage years. Cascade testing of offspring of people with hemochromatosis is widely advocated because it is an easily preventable disease. The ideal age to test those offspring is a matter of debate. Some authorities advocate testing at a very young age whereas others recommend delaying testing until late teenage years. To date there has been no published overview of the objective evidence and arguments central to this debate. In children who are C282Y homozygous, iron overload is rare in the first two decades of life and associated morbidity has only been documented in 1 patient. In the cascade setting, genetic testing for hemochromatosis need not be offered until late teenage years.
Publisher: SAGE Publications
Date: 10-2004
DOI: 10.3727/000000004783983341
Abstract: Metabolic liver diseases are excellent targets for correction using novel stem cell, hepatocyte, and gene therapies. In this study, the use of bone marrow stem cell transplantation to correct liver disease in the toxic milk (tx) mouse, a murine model for Wilson's disease, was evaluated. Preconditioning with sublethal irradiation, dietary copper loading, and the influence of cell transplantation sites were assessed. Recipient tx mice were sublethally irradiated (4 Gy) prior to transplantation with bone marrow stem cells harvested from normal congenic (DL) littermates. Of 46 transplanted tx mice, 11 demonstrated genotypic repopulation in the liver. Sublethal irradiation was found to be essential for donor cell engraftment and liver repopulation. Dietary copper loading did not improve cell engraftment and repopulation results. Both intravenously and intrasplenically transplanted cells produced similar repopulation successes. Direct evidence of functionality and disease correction following liver repopulation was observed in the 11 mice where liver copper levels were significantly reduced when compared with mice with no liver repopulation. The reversal of copper loading with bone marrow cells is similar to the level of correction seen when normal congenic liver cells are used. Transplantation of bone marrow cells partially corrects the metabolic phenotype in a mouse model for Wilson's disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-03-2009
DOI: 10.1002/HEP.22972
Publisher: Mary Ann Liebert Inc
Date: 2013
Abstract: Hemochromatosis is a common disorder of iron overload most commonly due to homozogosity for the HFE C282Y substitution. A workplace-screening program was conducted in which over 11,000 in iduals were screened for this mutation. A substudy of this project was to ascertain why people chose not to attend information and screening sessions offered in their workplace. Staff were recruited by email, questionnaires in common areas, and direct approach. A purpose-designed questionnaire sought the reasons for not attending information and screening sessions. The nonattender questionnaire was distributed at 24 workplaces and completed by 872 in iduals. The most common reason for not attending sessions, accounting for 70.1%, was practical (e.g., unaware of session, too busy, or unavailable). Other relatively common reasons were that the in idual had low iron levels or were a blood donor (14.9%), or that hemochromatosis was considered unimportant (12.2%). Insurance concerns were very rarely cited as the reason for nonattendance (1.0%). The nonattender data presented here indicate that concerns about insurance, anxiety, and use of genetic information are not major factors for why people did not attend workplace information and screening sessions for hereditary hemochromatosis. Practical barriers were the major reasons identified. This highlights that when implementing screening programs, as many practical barriers as possible need to be overcome, so that a maximum number of people who would like to be informed about screening are given the opportunity to do so.
Publisher: Wiley
Date: 11-10-2017
DOI: 10.1111/PAI.12651
Abstract: The march from early aeroallergen sensitization to subsequent respiratory allergy is well established, but it is unclear whether early life food sensitization precedes and further increases risk of allergic airway disease. To assess the association between food sensitization in the first 2 years of life and subsequent asthma and allergic rhinitis by age 10-12 years. We used data from two independent cohorts: the high-risk Melbourne Atopic Cohort Study (MACS) (n = 620) and the population-based LISAplus (n = 3094). Food sensitization was assessed at 6, 12, and 24 months in MACS and 24 months in LISAplus. Multiple logistic regressions were used to estimate associations between sensitization to food only, aeroallergen only, or both and allergic airway disease. When compared to non-sensitized children, sensitization to food only at 12 months in MACS and 24 months in LISAplus was associated with increased risk of current asthma (aOR = 2.2 95% CI 1.1, 4.6 in MACS and aOR = 4.9 2.4, 10.1 in LISAplus). Similar results were seen for allergic rhinitis. Additionally, cosensitization to food and aeroallergen in both cohorts at any tested point was a stronger predictor of asthma (at 24 months, aOR = 8.3 3.7, 18.8 in MACS and aOR = 14.4 5.0, 41.6 in LISAplus) and allergic rhinitis (at 24 months, aOR = 3.9 1.9, 8.1 in MACS and aOR = 7.6 3.0, 19.6 in LISAplus). In both cohorts, food sensitization (with or without aeroallergen sensitization) in the first two years of life increased the risk of subsequent asthma and allergic rhinitis. These findings support the role of early life food sensitization in the atopic march and suggest trials to prevent early onset have the potential to reduce the development of allergic airways disease.
Publisher: Wiley
Date: 21-05-2017
DOI: 10.1111/CEA.12942
Abstract: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells. Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located s le of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication s le phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. IL13 rs1295686 was associated with challenge-proven food allergy in the discovery s le (P=.003 OR=1.75 CI=1.20-2.53). This association was also detected in the replication s le (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE. We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
Publisher: Wiley
Date: 10-09-2015
DOI: 10.1111/PDE.12685
Abstract: The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.
Publisher: Wiley
Date: 14-08-2018
DOI: 10.1111/CEA.13235
Abstract: Asian children born in Australia have higher rates of eczema and nut allergy than non-Asian children. However, it is not known whether this country of birth differential exists for other allergies or anaphylaxis risk. We investigated the influence of maternal and child's country of birth on the prevalence of parent-reported eczema, asthma, food allergy and being diagnosed by a doctor as being "at risk of anaphylaxis." We assessed the relationship between mother and child country of birth and allergies using the 2010 School Entrant Health Questionnaire, completed for 57 005 5-year old children (85.8% response rate) in Victoria, Australia. Analyses were conducted using logistic regression with results presented as odds ratios (OR) with 95% confidence intervals (CIs). Children born in Australia to Asian-born mothers were more likely to have parent-reported food allergy (OR 2.33, 95%CI 1.96-2.77) and eczema (OR 2.04, 95%CI 1.73-2.41), but not more likely to have asthma (OR 0.87, 95% CI 0.74-1.02) than non-Asian children. By contrast, children born in Asia who subsequently migrated to Australia had a lower risk of food allergy (OR 0.33, 95%CI 0.20-0.55), eczema (OR 0.37, 95%CI 0.24-0.57) and asthma (OR 0.29, 95% CI 0.21-0.40). Patterns of anaphylaxis risk differed depending on the trigger. Compared with Australian-born non-Asian children, Australian-born Asian children were more likely to be diagnosed as being at risk of both food-induced and non-food-induced anaphylaxis. For children born in Asia, risk was lower for anaphylaxis to milk, peanut and tree nuts compared to non-Asian children, but higher for soy, wheat and non-food triggers. Patterns of allergy/anaphylaxis risk and their triggers differed according to both ethnicity and country of birth, suggesting a gene-environment factor is in play. The difference in patterns for asthma compared with other atopic diseases is surprising and warrants further exploration.
Publisher: Elsevier BV
Date: 04-2012
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.TRIM.2005.09.001
Abstract: Stem cells tantalise. They alone have the capacity to ide exponentially, recreate the stem cell compartment as well as create differentiated cells to build tissues. They should be the natural candidates to provide a renewable source of cells for transplantation. Does the reality support the promise of this exciting alternative to conventional therapies for metabolic and degenerative liver disease? Can techniques be developed to provide the large number of cells that could be required? Must there be "space" in the liver to accept the cells? To what extent is the liver immunoprivileged, and is immunosuppression necessary for stem cell therapy? Is it better to use haematopoietic stem cells, fetal stem cells, mesenchymal cells, embryonic stem cells, hepatocytes or all of the above, but for different disease indications? This paper discusses why the exploration of stem cells for the treatment of liver disease is of great potential, and delineates some of the hurdles that need to be overcome before patients see benefits from laboratory-based research into stem cell transplantation and function.
Publisher: Elsevier BV
Date: 2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2013
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JACI.2018.07.038
Abstract: Longitudinal population-based data regarding tree nut allergy are limited. We sought to determine the population prevalence of tree nut allergy at age 6 years and explore the relationship between egg and peanut allergy at age 1 year and development of tree nut allergy at age 6 years. A population-based s le of 5276 children was recruited at age 1 year and followed up at age 6 years. At age 1 year, allergies to egg and peanut were determined by means of oral food challenge, and parents reported their child's history of reaction to tree nuts. Challenge-confirmed tree nut allergy was assessed at age 6 years. At age 1 year, the prevalence of parent-reported tree nut allergy was 0.1% (95% CI, 0.04% to 0.2%). Only 18.5% of infants had consumed tree nuts in the first year of life. At age 6 years, challenge-confirmed tree nut allergy prevalence was 3.3% (95% CI, 2.8% to 4.0%), with cashew the most common (2.7% 95% CI, 2.2% to 3.3%). Of children with peanut allergy only at age 1 year, 27% (95% CI, 16.1% to 39.7%) had tree nut allergy at age 6 years compared with 14% (95% CI, 10.4% to 17.9%) of those with egg allergy only and 37% (95% CI, 27.2% to 47.4%) of those with both peanut and egg allergy. Tree nut allergy is uncommon in the first year of life, likely because of limited tree nut consumption. At age 6 years, tree nut allergy prevalence is similar to peanut allergy prevalence. More than a third of children with both peanut and egg allergy in infancy have tree nut allergy at age 6 years. Understanding how to prevent tree nut allergy should be an urgent priority for future research.
Publisher: Oxford University Press (OUP)
Date: 30-03-2015
DOI: 10.1093/IJE/DYV026
Abstract: The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n = 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2- and 4-year reviews under way. Biological s les and measures include: maternal blood, faeces and urine during pregnancy infant urine, faeces and blood at regular intervals during the first 4 years lung function at 1 month and 4 years cardiovascular assessment at 1 month and 4 years skin-prick allergy testing and food challenge at 1 year and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [peter.vuillermin@deakin.edu.au].
Publisher: Wiley
Date: 25-01-2011
DOI: 10.1111/J.1399-3038.2011.01139.X
Abstract: Over the past three decades, the prevalence of allergic diseases has markedly increased in developed countries. There has been a paucity of data on food allergy (FA) in developing countries such as China. We aimed to estimate the prevalence and the clinical features of FA in Chinese infants attending a routine well-baby clinic in Chongqing, China. From January 1st to February 28th, 2009, consecutive infants and young children aged 0-12 months attending routine well-baby checks at the Department of Primary Child Care, Children's Hospital of Chongqing Medical University, were invited to participate in the study. Parents completed questionnaires, and children were skin prick tested (SPT) to a panel of 10 foods (egg white, egg yolk, cow's milk, soybean, peanut, wheat, fish, shrimp, orange, and carrot) together of histamine and saline controls. Subjects with either a positive SPT or a positive medical history were invited to undergo an oral food challenge. Of 497 children who consented to participate, 477 (96%) participated fully in the study. Of these, 56 subjects had a positive SPT (11.3%), with 45 positive to egg, 13 to cow's milk, 2 to peanut, 1 to fish, shrimp, and orange respectively. Eighty subjects (16.1%, 80/497) participated in food challenges. The overall prevalence of challenge-proven FA in 0- to 1-yr-old children in Chongqing, China, was 3.8% (18/477, 95% CI, 2.5-5.9%) with 2.5% (12/477) egg allergic and 1.3% (6/477) cow's milk allergic.
Publisher: BMJ
Date: 04-1999
DOI: 10.1136/JME.25.2.209
Abstract: The increasing availability of DNA-based diagnostic tests has raised issues about whether these should be applied to the population at large in order to identify, treat or prevent a range of diseases. DNA tests raise concerns in the community for several reasons. There is the possibility of stigmatisation and discrimination between those who test positive and those who don't. High-risk in iduals may be identified for whom no proven effective intervention is possible, or conversely may test "positive" for a disease that does not eventuate. Controversy concerning prenatal diagnosis and termination of affected pregnancies may arise. Haemochromatosis, however, is a disease that is not only treatable but also preventable if those at high risk are identified presymptomatically. This paper will identify and discuss key issues regarding DNA-based population screening for haemochromatosis, and argue that population-based genetic screening for haemochromatosis should be supported when a number of contentious issues are addressed. In the context of a health system with limited resources haemochromatosis is the paradigm of a disorder where there is an ethical and clinical imperative to encourage presymptomatic DNA testing for all in ethnically relevant communities.
Publisher: Massachusetts Medical Society
Date: 25-08-2016
DOI: 10.1056/NEJMC1607281
Publisher: Wiley
Date: 08-10-2004
DOI: 10.1111/J.1440-1746.2004.03451.X
Abstract: The toxic milk (tx) mouse is a non-fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper-transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype. Congenic hepatocytes were isolated and intrasplenically transplanted into 3-4-month-old tx mice, which were then placed on various copper-loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age-matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy. Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 +/- 68 microg/g, n = 11) compared to non-repopulated animals (866 +/- 62 microg/g, n = 14) and untreated controls (910 +/- 103 microg/g, n = 6 P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged. Transplanted liver cells can proliferate and correct a non-fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JAIP.2017.11.018
Abstract: Although food allergy has probably risen over recent decades, recent reports suggest that the prevalence of food sensitization in the general population has not changed. However, this has not been analyzed in infants at high risk of food allergy. The objective of this study was to compare the prevalence of food sensitization in high-risk infants from 2 cohorts recruited 15 years apart in the same region. This study includes 620 high-risk infants with a family history of allergy (Melbourne Atopy Cohort Study [MACS]) born 1990-1994, and a subgroup of high-risk infants from the population-based HealthNuts study (n = 3,661/5,276), born 2006-2010. Both studies undertook skin prick tests (SPT) to peanut, egg, and milk at age 12 months. A logistic regression model generated adjusted prevalences to account for differences in s ling frame. SPT ≥ 95% positive predictive values (PPVs) for food allergy were used as proxies for food allergy. The adjusted prevalence of sensitization in MACS was similar to the observed prevalence of sensitization in the high-risk subgroup of HealthNuts: 7.9% (95% confidence interval 6.8-8.9) and 7.9% (7.0-8.8) respectively for peanut, 15.0% (13.4-16.6) and 14.5% (13.4-15.7) respectively for egg, and 2.4% (1.6-3.1) and 2.6% (2.0-3.4) respectively for cow's milk. The prevalence of SPT ≥ 95% PPVs was similar between the 2 studies. The prevalence of food sensitization among high-risk infants has remained stable in Australia since the 1990s, despite the reported increase in food-related anaphylaxis in the same period. This discrepancy could be due to increased food allergy in the low-risk population, increased conversion of food sensitization to allergy, or increased number of high-risk infants. Alternatively, increased awareness or severity of reactions may have led to an apparent increase in food allergy.
Publisher: Wiley
Date: 11-2014
DOI: 10.1111/PAI.12301
Abstract: IgE-mediated egg allergy presents as one of the most common food allergies in children and is a food which is widely consumed all over the world. Measurement of egg white-specific IgE levels has been shown to be a poor predictor of clinical phenotypes of egg allergy, including to raw egg white, but particularly to baked or cooked egg. Egg white and yolk contain more than 20 different glycoproteins, including ovomucoid, ovalbumin, ovotransferrin, alpha-livetin, and the newly identified Gal d 6. Recent developments in component-resolved diagnostic technology, including microarrays, have enabled us to improve the way in which we diagnose food allergy. This technology allows us to measure specific IgE antibodies to in idual egg allergens which have been highly purified. Characterization of the major egg allergens could help profile the relevant binding epitopes to each region and may also help diagnose the different clinical phenotypes of egg allergy.
Publisher: No publisher found
Date: 2016
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JACI.2015.01.002
Abstract: 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.
Publisher: BMJ
Date: 03-2019
DOI: 10.1136/BMJOPEN-2018-024594
Abstract: The skin is an important barrier against environmental allergens, but infants have relatively impaired skin barrier function. There is evidence that impaired skin barrier function increases the risk of allergic sensitisation, atopic dermatitis (AD) and food allergy. We hypothesise that regular prophylactic use of emollients, particularly those that are designed to improve skin barrier structure and function, will help prevent these conditions. With the aim of determining if application of a ceramide-dominant emollient two times per day reduces the risk of AD and food allergy, we have commenced a multicentre phase III, outcome assessor blinded, randomised controlled trial of this emollient applied from birth to 6 months. Infants (n=760) with a family history of allergic disease will be recruited from maternity hospitals in Melbourne. The primary outcomes are as follows: the presence of AD, assessed using the UK Working Party criteria, and food allergy using food challenge, in the first 12 months of life as assessed by a blinded study outcome assessor. Secondary outcomes are as follows: food sensitisation (skin prick test), skin barrier function, AD severity, the presence of new onset AD after treatment cessation (between 6 and 12 months) and the presence of parent reported AD/eczema. Recruitment commenced in March 2018. The PEBBLES Study is approved by the Human Research Ethics Committees of the Royal Children’s Hospital (RCH) (#37090A) and the Mercy Hospital for Women (2018–008). Parents or guardians will provide written informed consent. Outcomes will be disseminated through peer-reviewed publications and presented at scientific conferences. ACTRN12617001380381 and NCT03667651 .
Publisher: Informa UK Limited
Date: 17-07-2020
Publisher: Medical Journals Sweden AB
Date: 2017
Abstract: Although wool is commonly believed to cause irritant (non-immune) and hypersensitivity (immune) cutaneous reactions, the evidence basis for this belief and its validity for modern garments have not been critically examined. Publications from the last 100 years, using MEDLINE and Google Scholar, were analysed for evidence that wool causes cutaneous reactions, both immune-mediated (atopic dermatitis exacerbation, contact urticaria, allergic contact dermatitis) and non-immune-mediated (irritant contact dermatitis, itch). Secondary aims of this paper were to examine evidence that lanolin and textile-processing additives (formaldehyde, chromium) cause cutaneous reactions in the context of modern wool-processing techniques. Current evidence does not suggest that wool-fibre is a cutaneous allergen. Furthermore, contact allergy from lanolin, chromium and formaldehyde is highly unlikely with modern wool garments. Cutaneous irritation from wool relates to high fibre diameters (≥ 30-32 µm). Superfine and ultrafine Merino wool do not activate sufficient c-fibres to cause itch, are well tolerated and may benefit eczema management.
Publisher: Elsevier BV
Date: 11-2001
Publisher: Springer Science and Business Media LLC
Date: 10-2006
DOI: 10.1007/S10534-005-5918-5
Abstract: The toxic milk (tx) mouse is a rodent model for Wilson disease, an inherited disorder of copper overload. Here we assessed the effect of copper accumulation in the tx mouse on zinc and iron metabolism. Copper, zinc and iron concentrations were determined in the liver, kidney, spleen and brain of control and copper-loaded animals by atomic absorption spectroscopy. Copper concentration increased dramatically in the liver, and was also significantly higher in the spleen, kidney and brain of control tx mice in the first few months of life compared with normal DL mice. Hepatic zinc was increased with age in the tx mouse, but zinc concentrations in the other organs were normal. Liver and kidney iron concentrations were significantly lower at birth in tx mice, but increased quickly to be comparable with control mice by 2 months of age. Iron concentration in the spleen was significantly higher in tx mice, but was lower in 5 day old tx pups. Copper-loading studies showed that normal DL mice ingesting 300 mg/l copper in their diet for 3 months maintained normal liver, kidney and brain copper, zinc and iron levels. Copper-loading of tx mice did not increase the already high liver copper concentrations, but spleen and brain copper concentrations were increased. Despite a significant elevation of copper in the brain of the copper-loaded tx mice no behavioural changes were observed. The livers of copper-loaded tx mice had a lower zinc concentration than control tx mice, whilst the kidney had double the concentration of iron suggesting that there was increased erythrocyte hemolysis in the copper-loaded mutants.
Publisher: Wiley
Date: 08-09-2010
DOI: 10.1111/J.1365-2222.2010.03562.X
Abstract: The incidence of hospital admissions for food allergy-related anaphylaxis in Australia has increased, in line with world-wide trends. However, a valid measure of food allergy prevalence and risk factor data from a population-based study is still lacking. To describe the study design and methods used to recruit infants from a population for skin prick testing and oral food challenges, and the use of preliminary data to investigate the extent to which the study s le is representative of the target population. The study s ling frame design comprises 12-month-old infants presenting for routine scheduled vaccination at immunization clinics in Melbourne, Australia. We compared demographic features of participating families to population summary statistics from the Victorian Perinatal census database, and administered a survey to those non-responders who chose not to participate in the study. Study design proved acceptable to the community with good uptake (response rate 73.4%), with 2171 participants recruited. Demographic information on the study population mirrored the Victorian population with most the population parameters measured falling within our confidence intervals (CI). Use of a non-responder questionnaire revealed that a higher proportion of infants who declined to participate (non-responders) were already eating and tolerating peanuts, than those agreeing to participate (54.4% 95% CI 50.8, 58.0 vs. 27.4% 95% CI 25.5, 29.3 among participants). A high proportion of in iduals approached in a community setting participated in a food allergy study. The study population differed from the eligible s le in relation to family history of allergy and prior consumption and peanut tolerance, providing some insights into the internal validity of the s le. The study exhibited external validity on general demographics to all births in Victoria.
Publisher: MDPI AG
Date: 08-01-2019
Abstract: Vitamin D is critical to children’s skeletal development and health. Despite this, the factors which determine vitamin D concentrations during infancy remain incompletely understood. This article reviews the literature assessing the factors which can affect vitamin D status in infancy, including antenatal and postnatal vitamin D supplementation. Observational data supports that dietary intake of vitamin D, UV exposure, and geographic factors contribute significantly to infants’ vitamin D status, but the relationship is unclear regarding genetic variation, ethnicity, and maternal vitamin D status. Randomised controlled trials have compared higher versus lower doses of infant vitamin D supplementation, but no studies have compared infant vitamin D supplementation to placebo and eliminated external sources of vitamin D to fully quantify its effect on vitamin D status. Knowledge gaps remain regarding the factors associated with optimal vitamin D concentrations in infants—including key factors such as ethnicity and genetic variation—and further studies are needed.
Publisher: Elsevier BV
Date: 2012
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JACI.2017.09.012
Abstract: Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group. We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based s le of schools (SchoolNuts, n = 9663 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year. Of 547 students with possible IgE-mediated food allergy, 243 (44.4% 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7% 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]). Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions.
Publisher: Elsevier BV
Date: 02-2015
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JACI.2017.09.015
Abstract: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. We sought to investigate genetic susceptibility to PA. Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10 This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.
Publisher: Informa UK Limited
Date: 05-03-2013
DOI: 10.3109/14015439.2013.775332
Abstract: Assessment for the purpose of monitoring change over time requires a different practical and statistical approach to that of assessment for diagnosing impairment. Sophisticated methods exist for identifying strengths and weaknesses in a patient's voice/speech profile, yet our understanding of the impact of repeated assessment is limited. Monitoring change necessitates that stimuli are stable in the absence of any true change in functioning, while remaining sensitive to influences that are considered to alter functioning (degeneration, therapy). The current paper discusses the issues relating to stimuli selection, identifying error within the s le and appropriate statistical models for identifying intra-in idual change in the context of clinical and experimental speech or voice examinations.
Publisher: Elsevier BV
Date: 03-2012
Publisher: Elsevier BV
Date: 07-2015
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAIP.2018.07.042
Abstract: We previously reported that infants with Asian-born parents are 3 times more likely to have IgE-mediated food allergy than those with Australian-born parents. It is unknown whether this translates to the increased risk of other allergic diseases later in childhood and whether ancestry interacts with other risk factors for allergic disease development. To compare prevalence and risk factors for allergic rhinitis, asthma, and aeroallergen sensitization at age 6 between children with East Asian-born and Caucasian-born parents. A total of 5276 1-year-old infants were recruited into a population-based longitudinal study of allergy. A total of 4455 children participated in age 6 follow-up (84.4%), including 3015 with Caucasian-born parents and 415 with East Asian-born parents. Children underwent skin prick tests to aeroallergens and questionnaires captured data on asthma, eczema, and allergic rhinitis. Compared with children with Caucasian-born parents, children of East Asian-born parents had more allergic rhinitis (19.9% [95% confidence interval (CI) 14.9-26] vs 9.3% [95% CI 8-10.8], P < .001) and aeroallergen sensitization (64.3% [95% CI 57.5-70.5] vs 34.4% [95% CI 32.2-36.7], P < .001) at age 6. Asthma was similar in both groups (9.1% [95% CI 6.2-13.2] vs 11.7% [95% CI 10.4-13.1]), P = .21. 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, irrespective of ancestry. Children of East Asian ancestry born in Australia have a higher burden of most allergic diseases in the first 6 years of life, whereas asthma may follow a different pattern. IgE-mediated food allergy and eczema at age 1 increase the risk of asthma and allergic rhinitis irrespective of ancestry.
Publisher: Elsevier
Date: 2012
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JACI.2017.05.041
Abstract: Rising rates of food-induced anaphylaxis have recently been shown in the adolescent age group, following earlier descriptions of a rise in children younger than 5 years. However, few population-based studies have examined the prevalence of food allergy in adolescence using objective measures such as oral food challenge (OFC). We sought to determine the prevalence of food allergy among a population-based s le of 10- to 14-year-old adolescents using clinical evaluation including OFC to confirm the diagnosis. Schools were randomly selected from greater metropolitan Melbourne, Australia. Students aged 10 to 14 years, and their parents, were asked to complete a questionnaire regarding the adolescent's food allergy or food-related reactions. Clinic evaluation, which consisted of skin prick tests and OFC where eligible, was undertaken if students were suspected to have current food allergy from parent response. Among 9816 students assessed, 5016 had complete parent response and clinic evaluation when eligible. An additional 4800 students had student questionnaires only. The prevalence of clinic-defined current food allergy based on history, sensitization data, and OFC results was 4.5% (95% CI, 3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3-3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800 adolescents who had only self-reported food allergy status available, the prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most common. Approximately 1 in 20 10- to 14-year-old school students in Melbourne has current food allergy. This high prevalence suggests that the previously reported rise in food-induced anaphylaxis in this age group may reflect an increasing prevalence of food allergy rather than simply increased reporting of anaphylaxis.
Publisher: Wiley
Date: 24-10-2017
DOI: 10.1111/ALL.13300
Abstract: Dietary polyunsaturated fatty acids (PUFAs) have immunoregulatory properties. Breast milk is rich in PUFA, and it has been hypothesized that these PUFAs may be important in the aetiology of allergic diseases. Despite a growing body of evidence, the associations between breast milk PUFA and allergic disease have not previously been systematically reviewed. The search was performed in PubMed and EMBASE databases using breastfeeding, fatty acid and allergic disease terms. Two authors were involved in selecting papers for review according to the inclusion criteria and extracting information on study characteristics and measures of association. Only studies that reported numeric associations between concentration of breast milk fatty acids and allergic disease outcomes were included. A total of 18 papers met the inclusion criteria, reporting results from 15 study populations. The majority were cohort studies (n=11), with data from only two case-control and two cross-sectional studies. S le size varied between 30 and 352 participants, and follow-up time of the cohorts varied between 3 months and 14 years. Nine studies reported on eczema, seven reported on sensitization, and only five reported on asthma/wheeze. There was heterogeneity among studies in terms of presenting the association between PUFA and allergy therefore, estimates could not be pooled. Only a few studies observed associations between n-3 and n-6 PUFAs and allergic disease, and the magnitude of this effect varied greatly. There is insufficient evidence to suggest that colostrum or breast milk polyunsaturated fatty acids influence the risk of childhood allergic diseases.
Publisher: Wiley
Date: 04-09-2013
DOI: 10.1111/ALL.12215
Abstract: Sensitization to food allergens indicates the production of food-specific IgE however, sensitization is not a definite indicator of allergic reaction upon ingestion (N Engl J Med, 344, 2001, 30: J Allergy Clin Immunol, 120, 2007, 491). Currently, food challenge is the best approach to identify the presence or absence of allergy. While 95% positive predictive values (PPVs) thresholds for sIgE can assist with identifying increased likelihood of allergy among those who are sensitized, there are no specific biological markers that differentiate between allergic and sensitized in iduals. To determine whether plasma serum cytokine profiles predict (i) sensitization to peanut and egg and (ii) food allergy among sensitized infants. Peanut-sensitized (PT) and egg-sensitized 14-month-old infants and nonsensitized controls enrolled in HealthNuts, a population-based study of food allergy, underwent an oral food challenge (OFC). Blood was collected within 1 h after OFC. Serum levels of Th1, Th2 and regulatory cytokines were determined in allergic (n = 79), sensitized (n = 40) and nonsensitized, nonallergic (n = 37) infants by multiplex assay. Food-sensitized infants had significantly higher plasma IL-4, IL-13, IL-12p70 and lower IL-10 levels compared to nonsensitized infants. IL-10 and IL-6 levels were significantly higher in sensitized compared with allergic infants. Egg-allergic infants had significantly higher IL-13 and IL-12p70 levels compared to peanut-allergic (PA) infants. Levels of Th2-related cytokines in plasma are higher in food-sensitized infants, irrespective of clinical food allergy status. In contrast, IL-10 levels appear to predict food allergy among sensitized infants. Differences in IL-13 and IL-12p70 between egg- and peanut-allergic infants could help explain the different resolution rates of the allergies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-03-2015
DOI: 10.1002/HEP.27711
Abstract: To identify polymorphisms associated with variability of iron overload severity in HFE ‐associated hemochromatosis, we performed exome sequencing of DNA from 35 male HFE C282Y homozygotes with either markedly increased iron stores (n = 22 cases) or with normal or mildly increased iron stores (n = 13 controls). The 35 participants, residents of the United States, Canada, and Australia, reported no or light alcohol consumption. Sequencing data included 82,068 single‐nucleotide variants, and 10,337 genes were tested for a difference between cases and controls. A variant in the GNPAT gene showed the most significant association with severe iron overload ( P = 3 × 10 −6 P = 0.033 by the likelihood ratio test after correction for multiple comparisons). Sixteen of twenty‐two participants with severe iron overload had glyceronephosphate O‐acyltransferase ( GNPAT ) polymorphism p.D519G (rs11558492 15 heterozygotes, one homozygote). No control participant had this polymorphism. To examine functional consequences of GNPAT deficiency, we performed small interfering RNA–based knockdown of GNPAT in the human liver‐derived cell line, HepG2/C3A. This knockdown resulted in a ‐fold decrease in expression of the messenger RNA encoding the iron‐regulatory hormone, hepcidin. Conclusion: GNPAT p.D519G is associated with a high‐iron phenotype in HFE C282Y homozygotes and may participate in hepcidin regulation. (H epatology 2015 :429–439
Publisher: Wiley
Date: 31-08-2013
DOI: 10.1111/ALL.12216
Abstract: Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood. In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy. Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88 1.26-6.58), especially in those who received simultaneous BCG (5.99 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45 1.20-4.96). There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy. Clinicaltrials.gov NCT 01420705.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2014
End Date: 2016
Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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