Paediatrics (RCH) - Research Publications
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ItemThe association between environmental greenness and the risk of food allergy: A population-based study in Melbourne, Australia(WILEY, 2022-02)BACKGROUND: While exposure to environmental greenness in childhood has shown mixed associations with the development of allergic disease, the relationship with food allergy has not been explored. We investigated the association between exposure to environmental greenness and challenge-confirmed food allergy in a large population-based cohort. METHODS: The HealthNuts study recruited 5276 12-month-old infants in Melbourne, Australia, who underwent skin prick testing to peanut, egg, and sesame; infants with a detectable wheal underwent food challenges to determine food allergy status. Environmental greenness was estimated using the normalized difference vegetation index (NDVI) for five buffer zones around the infant's home address: at the home, 100 m, 500 m, 800 m, and 1600 m radial distances. Environmental greenness was categorized into 3 tertiles and mixed effects logistic regression models quantified the association between greenness and the risk of food allergy, adjusting for confounding and accounting for clustering at the neighborhood level. RESULTS: NDVI data were available for n = 5097. For most buffer zones, medium and high greenness, compared to low greenness, was associated with an increased risk of peanut allergy (eg, 100 m tertile 2 aOR 1.89 95% CI 1.22-2.95, tertile 3 aOR 1.78 95% CI 1.13-2.82). For egg allergy, the effect sizes were smaller (100 m tertile 2 aOR 1.52 95% CI 1.16-1.97, tertile 3 aOR 1.38 95% CI 1.05-1.82). Socioeconomic status (SES) modified the association between greenness and peanut allergy, but not egg allergy; associations were apparent in the low SES group but not in the high SES group (p for interaction 0.08 at 100 m). Air pollution (PM2.5) also modified the associations between environmental greenness and food allergy, with associations present in high air pollution areas but not low (p for interaction at 100 m 0.05 for peanut and 0.06 for egg allergy.) CONCLUSION: Increased exposure to environmental greenness in the first year of life was associated with an increased risk of food allergy. Increased greenness may correlate with higher pollen levels which may trigger innate immune responses skewing the immune system to the Th2-dependent allergic phenotype; additionally, some pollen and food allergens are cross-reactive. Given the mixed data on greenness and other allergies, the relationship appears complex and may also be influenced by confounding variables outside those that were measured in this study.
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ItemRevisiting the Atopic March Current Evidence(AMER THORACIC SOC, 2022-10-15)
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ItemThe association between domestic hard water and eczema in adults from the UK Biobank cohort study(OXFORD UNIV PRESS, 2022-11)BACKGROUND: Eczema is a chronic inflammatory skin disease. Domestic water with high mineral content (hard water) is a risk factor for eczema in children, but this association has not been assessed in adults. OBJECTIVES: To examine the association between domestic hard water supply and eczema prevalence and incidence in adults aged 40-69 years and the contextual effect in eczema outcomes by postcode in adults in the UK. METHODS: We used data from the UK Biobank study collected in 2006-10 (baseline) and 2013-14 (follow-up). Eczema prevalence at baseline (2006-10) and at follow-up (2013-14) and incidence (new onset between baseline and follow-up) were determined from the touchscreen questionnaires and nurse-led interviews. Domestic hard water information was obtained in 2005 and 2013 from the local water supply companies in England, Wales and Scotland as CaCO3 concentrations. We fitted multilevel logistic regression models with random intercepts for postcode areas to examine the effect of domestic hard water on eczema outcomes, and we measured components of variance. RESULTS: In total, 306 531 participants with a mean age of 57 years nested across 7642 postcodes were included in the baseline analysis, and 31 036 participants nested across 3695 postcodes were included in the follow-up analysis. We observed an increase in the odds of eczema at baseline [odds ratio (OR) 1·02, 95% confidence interval (CI) 1·01-1·04] per 50 mg L-1 of CaCO3 increase. Furthermore, exposure to domestic hard water (> 200 mg L-1 of CaCO3 ) was associated with increased odds of prevalent eczema at baseline (OR 1·12, 95% CI 1·04-1·22). Moreover, there was a significant linear trend (P < 0·001) in which increasing levels of hard water increased eczema prevalence risk. No association was observed with incident eczema or eczema at follow-up. The intraclass correlation coefficient for postcode was 1·6% (95% CI 0·7-3·4), which remained unexplained by area-level socioeconomic measures. CONCLUSIONS: Increasing levels of domestic hard water, as measured by CaCO3 concentrations, were associated with an increased prevalence of eczema in adults but not increased incidence. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing the burden of eczema in adults. Further research is needed to explore area-level factors that may lead to eczema. What is already known about this topic? Hard water is formed when minerals are dissolved in water from filtration through sedimentary rocks. Several studies have reported a higher prevalence of eczema in areas with hard water. However, all studies on this topic have assessed this in infants and school-aged children, while this association has not been explored in adults. What does this study add? Our findings suggest that exposure to higher concentrations of domestic hard water is associated with an increase in eczema prevalence in adults aged 40-69 years. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing eczema prevalence in adults.
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ItemThe role of short-term grass pollen exposure in food skin-prick test reactivity, food allergy, and eczema flares in children(WILEY, 2022-10)BACKGROUND: While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children. METHODS: We investigated 1- (n = 1108) and 6-year-old (n = 675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1 year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. RESULTS: Grass pollen at lag 0-3 (every 20 grains/m3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only. CONCLUSION: Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold.
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ItemAssociations between Body Mass Index Trajectories in the first two years of life and Allergic Rhinitis, Eczema and Food Allergy outcomes up to early adulthood(WILEY, 2022-03)BACKGROUND: Early life body mass index (BMI) trajectories influence the risk of asthma at 18 years of age. However, it is unclear if these are also associated with other allergic diseases. OBJECTIVES: We investigated the associations between BMI trajectories and subsequent allergic rhinitis, eczema and food sensitisation/allergies. METHODS: Parent-reported anthropometric data were collected 18 times in the first two years of life from a cohort of 620 participants in a high-risk cohort. Group-based trajectory modelling was applied to develop BMI trajectories. Associations between trajectories and allergic rhinitis, eczema and food sensitisation at 6, 12 and 18 years of age were assessed using logistic regression models. Potential effect modifications by parental allergic disease, sex and allocated infant formula were assessed. RESULTS: We identified five BMI trajectories: average, below average, persistently low, early low and catch up, and persistently high. None showed an association with allergic rhinitis. In participants with maternal allergic rhinitis, 'early-low and catch-up' (OR = 2.83;95%CI 1.34-5.96, Pint = 0.05) and 'below average' trajectories (OR = 2.39; 1.18-7.23, Pint = 0.02) were associated with allergic rhinitis at 18 years of age compared with the average trajectory. No associations were observed with eczema or food sensitisation. CONCLUSION: Infants with early-low and catch-up, or below average BMI growth, were at increased risk of allergic rhinitis at 18 years if they had a mother with allergic rhinitis. These results require replication, but suggest that interactions between poor intrauterine growth, failure to thrive and maternal allergies may influence the risk of allergic rhinitis.
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ItemIs antenatal or early-life vitamin D associated with eczema or food allergy in childhood? A systematic review(Wiley, 2023-05)OBJECTIVE: To summarise the associations between antenatal or early-life blood vitamin D and the development of eczema/food allergy in childhood. DESIGN: A systematic review and meta-analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SOURCES: We systematically searched PubMed and Embase from inception and April 2022. ELIGIBILITY CRITERIA: Human studies that investigated prospective associations between antenatal or early-life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. RESULTS: Forty-three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85; 0.67-1.08, I2 = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89; 0.84-0.94, I2 = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. CONCLUSIONS: We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, No. CRD42013005559.
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ItemNo Preview AvailableParental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring(MOSBY-ELSEVIER, 2022-07)BACKGROUND: Recent evidence suggests that parental exposures before conception can increase the risk of asthma in offspring. OBJECTIVE: We investigated the association between parents' preconception body mass index (BMI) trajectories from childhood to adolescence and subsequent risk of asthma in their offspring. METHODS: Using group-based trajectory modeling from the Tasmanian Longitudinal Health Study, we identified BMI trajectories for index participants (parents) when aged 4 years to 15 years. Multinomial regression models adjusted for potential confounders were utilized to estimate the association between these early-life parents' BMI trajectories and asthma phenotypes in their subsequent offspring. RESULTS: The main analysis included 1822 parents and 4208 offspring. Four BMI trajectories from age 4 years to 15 years were identified as the best-fitting model: low (8.8%), normal (44.1%), above normal (40.2%), and high (7.0%). Associations were observed between father's high BMI trajectory and risk of asthma in offspring before the age of 10 years (relative risk ratio [RRR] =1.70 [95% CI = 0.98-2.93]) and also asthma ever (RRR = 1.72 [95% CI = 1.00-2.97]), especially allergic asthma ever (RRR = 2.05 [95% CI = 1.12-3.72]). These associations were not mediated by offspring birth weight. No associations were observed for maternal BMI trajectories and offspring asthma phenotypes. CONCLUSION: This cohort study over 6 decades of life and across 2 generations suggests that the high BMI trajectory in fathers, well before conception, increased the risk of asthma in their offspring.
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ItemOut-of-hospital health care costs of childhood food allergy in Australia: A population-based longitudinal study(WILEY, 2022-11)BACKGROUND: Australia has one of the highest prevalence of childhood food allergy in the world, but there are no data on its economic burden in Australia. METHODS: We used data from the HealthNuts study, a population-based longitudinal study undertaken in Melbourne, Australia. Infants were recruited at age 12 months between Sept 2007 and Aug 2011 with food allergy diagnosed using oral food challenges. Health care costs of out-of-hospital services were collected through data linkage to Australia's universal health insurance scheme Medicare. Two-part model was used to compare costs after controlling for potential confounders. RESULTS: 2919 children were included, and 390 (13.4%) had challenge-confirmed food allergy at age 1 year. Compared with children without food allergy, children with food allergy had significantly higher costs for GP visits, specialist visits, tests, and prescriptions in the first four years of life. The total Medicare cost associated with food allergy from age 1 to 4 years was estimated to be AUD$889.7 (95% CI $566.1-$1188.3) or €411.0 (95% CI €261.5-€549.0) per child. This was projected into an annual Medicare cost of AUD$26.1 million (95% CI $20.1-$32.3 million) or €12.1 (95% CI €9.3-€14.9 million) based on population size in 2020. CONCLUSIONS: Childhood food allergy causes considerable Medicare costs for out-of-hospital services in the first four years after birth in Australia. These findings can help anticipate the financial impact on the health care system associated with childhood food allergy, act as a useful costing resource for future evaluations, and inform management of childhood food allergy internationally.
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ItemEarly-Life Antibiotic Exposure and Childhood Asthma Trajectories: A National Population-Based Birth Cohort(MDPI, 2023-02)INTRODUCTION: Early-life antibiotic exposure is common and impacts the development of the child's microbiome and immune system. Information on the impacts of early-life antibiotics exposure on childhood asthma is lacking. METHODS: This study examined associations between early-life (0-24 months) antibiotics exposure with childhood (6-15 years) asthma trajectories through the Australian Longitudinal Study of Australian Children (LSAC) and their linked data from the Pharmaceutical Benefits Scheme. Asthma phenotypes were derived by group-based trajectory modeling. RESULTS: Of 5107 LSAC participants, 4318 were included in the final analyses (84.6% retention). Four asthma phenotypes were identified: Always-low-risk (79.0%), early-resolving asthma (7.1%), early-persistent asthma (7.9%), and late-onset asthma (6.0%). Any early-life antibiotic exposure increased risk 2.3-fold (95% CI: 1.47-3.67; p < 0.001) for early-persistent asthma among all children. In subgroup analyses, early-persistent asthma risk increased by 2.7-fold with any second-generation cephalosporin exposure, and by 2-fold with any β-lactam other than cephalosporin or macrolide exposure. CONCLUSION: We concluded that early-life antibiotic exposure is associated with an increased risk of early-persistent childhood asthma. This reinforces scrutiny of early-life antibiotic use, particularly for common viral infections where no antibiotics are required.
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ItemCohort profile: the multigeneration Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort(BMJ PUBLISHING GROUP, 2022-06)PURPOSE: The Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort was established to (1) investigate how exposures before conception and in previous generations influence health and disease, particularly allergies and respiratory health, (2) identify susceptible time windows and (3) explore underlying mechanisms. The ultimate aim is to facilitate efficient intervention strategies targeting multiple generations. PARTICIPANTS: RHINESSA includes study participants of multiple generations from ten study centres in Norway (1), Denmark (1), Sweden (3), Iceland (1), Estonia (1), Spain (2) and Australia (1). The RHINESSA core cohort, adult offspring generation 3 (G3), was first investigated in 2014-17 in a questionnaire study (N=8818, age 18-53 years) and a clinical study (subsample, n=1405). Their G2 parents participated in the population-based cohorts, European Community Respiratory Heath Survey and Respiratory Health In Northern Europe, followed since the early 1990s when they were 20-44 years old, at 8-10 years intervals. Study protocols are harmonised across generations. FINDINGS TO DATE: Collected data include spirometry, skin prick tests, exhaled nitric oxide, anthropometrics, bioimpedance, blood pressure; questionnaire/interview data on respiratory/general/reproductive health, indoor/outdoor environment, smoking, occupation, general characteristics and lifestyle; biobanked blood, urine, gingival fluid, skin swabs; measured specific and total IgE, DNA methylation, sex hormones and oral microbiome. Research results suggest that parental environment years before conception, in particular, father's exposures such as smoking and overweight, may be of key importance for asthma and lung function, and that there is an important susceptibility window in male prepuberty. Statistical analyses developed to approach causal inference suggest that these associations may be causal. DNA methylation studies suggest a mechanism for transfer of father's exposures to offspring health and disease through impact on offspring DNA methylation. FUTURE PLANS: Follow-up is planned at 5-8 years intervals, first in 2021-2023. Linkage with health registries contributes to follow-up of the cohort.
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